Title of Invention

MORPHINAN DERIVATIVES THE QUATERNARY AMMONIUM SALTS THEREOF SUBSTITUTED IN POSITION 14

Abstract

ABSTRACT 3045/CHENP/2004 Morphinan derivatives the quaternary ammonium salts thereof substituted in position 14 The invention relates to a class of morphinan compounds and the quaternary ammonium salts thereof, substituted in position 14, which may be used as highly-active analgesics or also as opioid antagonists. The invention further relates to the pharmaceuticaily-acceptable salts and easily-produced derivatives thereof, a process for production thereof and use thereof in the production of pharmaceutical specialities.

Full Text

The present invention relates to a class of morphinan compounds and the quaternary salts thereof substituted in Position 14, which may be used as highly active analgesics or also as opioid antagonists. The present invention further relates to pharmaceutical^ acceptable salts and easily-produced derivatives thereof, a process of production thereof and use thereof in the' production of pharmaceutical specialities. The existence of opioid receptors as receptors of the central nervous system (CNS), which impart analgesic effects, has been clearly proven. These receptors are subdivided into three subtypes, u, K and 5. Activation of these receptors by opioid agonists leads to an analgesic effect. The activation of the u-receptors causes the highest analgesic effect, whereby particularly N-methyl substituted morphinans with an oxygen function in Position 6 (morphine, oxymorphone, hydromorphone, etc.) are particularly active opioid agonists and are used as effective analgesics. In the past a great deal of work has been invested in structure-activity relationship studies of this class of substance. In the Journal of Medicinal Chemistry 1984, 27, pp. 1575-1579 various 14-methoxy-N-methylmorphinan-6-ones a re d escribed w ith v arious s ubstituents i n Position 3. These derivatives show higher analgesic activity than their 14-hydroxy analogues. A detailed study of 5-methyloxymorphone (= t4-hydroxy-5-methyidihydromorphinone) is described in Helvetica Chimica Acta (1988,71, pp. 1801-1804), which arrives at the result that the introduction of a 5-methyl group reduces the opioid agonistic properties of oxymorphone. A further study of 14-alkoxy-N-methylmorphinan-6-ones is described in Helvetica Chimica Acta 1989, 72, pp. 1 233-1239, in whichthe influenceof various substituents in Position 3 and of the amino nitrogen have been evaluated. The German published patent application DE 34 12 727 describes 14-alkoxy-N-methylmorphinan-6-ones (14-O-alkyloxymorphones) with higher activity than their 14-hydroxy analogues. If instead of the N-methyl group, e.g. an N-cyclopropy I methyl group, an N-allyl group or an N-tetrahydrofurfuryl group is introduced, then normally compounds result which cause antagonistic effects on opioid receptors (see Prog. Med. Chem. 1998, 35, 83-132). Such opioid antagonists cancel both the analgesic effect as well as the side effects of opioid agonists (e.g. respiratory depression or obstipation). Surprisingly, it has now been found that e.g. N-cyclopropylmethyl, N-allyl or N-tetrahydrofurfuryl substituted morphinan-6-ones with arylalkyl substituents or longer chained alkyl substituents in Position 14 are highly active opioid agonists with excellent analgesic activity. The very high analgesic activity enables low dosing, which leads to a lower rate of side effects. Furthermore, its has been surprisingly found that a quatemisation of morphinan-6-ones, which exhibit arylalkyl substituents or alkyl substituents in Position 14, on one hand leads to substances with higher analgesic activity, but on the other hand to substances with excellent opioid antagonism. The previously described quatemisation of 14-hydroxymorphinan-6-ones (e.g. oxymorphone or naloxone)led to a significant weakening of the effectiveness (see M.A. lorio et a!., Eur. J. Med. Chem. - Chim. Ther. 1984,19, 301-303). Furthermore, it has been found that these new substances develop their effect primarily in the periphery, because they cannot, or can only to a slight extent, overcome the blood-brain barrier. The present invention provides highly active compounds of the formulae (I), (la), (IA) and (IAa) as defined in the Claims 1 and 2. Preferred embodiments are given in the subclaims, along with further aspects of this invention, such as compositions and uses. The statements made, in particular in conjunction with the compounds, about preferred embodiments apply analogously also to the other aspects of the invention, such as the compositions and uses. Additional preferred embodiments are defined in the following. Compounds of the formulae (I) and (la), in which the substituents have the following significance: Ri: CrC6-atkyl; C2-C6-alkenyl; C2-C6-alkinyl; C4-Cie-cycloalkylalkyl, where cycloalkyl is C3-C10 and alkyl is C!-C6; C5-Ci6-cycloalkylalkenyl, where cycloalkyl is C3-C10 and alkenyl is Cj-Cei C5-C16-cycloalkylalkinyl, where cycloalkyl is C3-C10 and alkinyl is CrC6; C7-Cie-arylalkyl, where aryl is C6-Cio-aryl and alkyl is Ct-C6-alkyl; CB-C16-arylalkenyl, where aryl is C6-C10-aryl and alkenyl is CZ-CB-alkenyl; C8-Ci6-arylalkinyl, where aryl is C6-C10-aryl and alkinyl is C2-C6-alkinyl; R2: subject to the following definition of X, C4-C6-alkyi; C2-C6-alkenyl; C2-C6-alkinyl; C4-C16-cycloalkylalkyl, where cycloalkyl is C3-Ci0 and alkyl is Ci-C6; C5-Ci6-cycloalkylalkenyl, where cycloalkyl is C3-Ci0 and alkenyl is C2-C6; C5-C-,6-cycloalkylalkinyl, where cycloalkyl is C3-Ci0 and alkinyl is C2-C6; C7-C16-arylalkyl, where aryl is C6-Ci0-aryl and alkyl is CrC6-alkyl; Cfl-C16-arylalkenyl, where aryl is C6-C10-aryl and alkenyl is C2-C6-alkenyl; C8-C16-arylalkinyl, where aryl is C6-do-aryl and alkinyl is C2-C6-aklinyl; C3-C6-alkenoyl; C3-C6-alkinoyl: C9-C16-arylalkenoyl, where aryl is C6-do-aryl and alkenoyl is C3-C6-alkenoyl; drde-ar/lalkinoyl, where aryl is C6-C10-aryl and alkinoyl is C3-Cg-aikinoyl; R3: hydrogen; d-Ce-alkyl; C2-C6-alkenyl; C7-C15-arylalkyl, where aryl is C6-C10-ary! and alkyl is d-Ce-alkyl; Ce-C16-arylalkenyl, where aryl is C6-C10-aryl and alkenyl is C2-C6-alkenyl; alkoxyalkyl, where alkoxy ts d-Cft-alkaxy and alkyl is CrC6-alkyl; C02(d-C6-alkyl); C02H; CH2OH. R4: hydrogen; hydroxy; Ci-C6-alkyloxy; C2-C10-alkyloxyalkoxy, where alkyloxy is d-d and alkoxy is d-C6-alkyloxy d-C6-alkyloxy; C2-C6-alkenyloxy; C2-C6-alkinyloxy; d-de-cycloalkyialkyloxy, where cycloalkyl is C3-do and alkyl is d-d; C5-Ci6-cycloalkylalkenyloxy, where cycloalkyl is Ca-do and alkenyl is C2-C6; Cg-de-cycloalkylalkinyloxy, where cycloalkyl is C3-do and alkinyl is C2-C6; d-de-arylalkyloxy, where aryl is Ce-C^-aryl and alkyl is Ci-CB-alkyl; CB_Ct6-arylalkenyloxy, where aryl is Ce-Cio-aryl and alkenyl is CrCe-alkenyl; C8-C,6-arylalkinyloxy. where aryl is C6-C10-aryl and alkinyl is C2-C6-alkinyl; d-d-alkanoyloxy; d-C6-alkenoyloxy; d-C6-alkinoyloxy; C7-C16-arylalkanoyloxy, where aryl is C6-do-aryl and alkanoyloxy is C,-C6-alkylanoyloxy; C9-Ci8-arylalkenoyloxy, where aryl is C6-C10-aryl and alkenoyloxy is C3-C6-alkenoyloxy; C7-C16-arylalkinoyloxy, where aryl is C6-C10-aryl and alkinoyloxy is C3-C6-alkinoyloxy; R5: hydrogen; hydroxy; d-d-alkyloxy; (Vdo-alkyloxyalkoxy, where alkyloxy is d-C4 and alkoxy is d-d-alkyloxy CrC6-alkyloxy; C2-C6-alkenyloxy; C2-C6-alkinyloxy; C4-C16-cycloalkylalkyloxy, where cycloalkyl is C3-do and alkyl is Ci-C6; C5-C1B-cycloalkylalkenyloxy, where cycloalkyl is C3-do and alkenyl is C2-C6; d-de-cycloalkylalkinyloxy, where cycloalkyl is d-do and alkinyl is C2'C6; C7-C16-arylalkyloxy, where aryl is C6-C,0-aryl and alkyl is d-d-alkyf; CB-C16-arylalkenyloxy, where aryl is Cfl-Cio-aryl and alkenyl is CrC6-alkenyl; C8-C16-arylalkinyloxy, where aryl is C6-C10-aryl and alkinyl is CrC6-alkinyl; d-Ce-alkanoyloxy; CrCi6-arylalkanoyloxy, where aryl is d-do-aryl and alkanoyloxy is Ci-Ce-alkylanoyloxy; X is oxygen, sulphur or methylene. In the present invention alkyl, alkenyl and alkinyl consist of branched or unbranched alkyl, alkenyl and alkinyl. Aryl can be unsubstituted or mono-, di- or trisubstituted independently with hydroxy, halogen, nitro, cyano, thiocyanato, trifluoromethyl, CrC3-alkyl, C1-C3-alkoxy, C02H, CONH2, CO2(d-d-alky0. CONHfd-Cralkyl), CON(Ci-C3-alkyl)2, CO(Ci-C3-alkyl); amino; (d-C3-monoalkyl)amino, (d-d- dialkyl)amino; d-d-cycloalkylamino, (C,-C3-alkanoyl)amido, SH, S03H, S03(d-d-aikyf), S02(d- Cs-alkyl). SO(C,-C3-alkyl), C,-C3-alkylthio or C,-C3-alkanoylthio. The above stated definitions for alkyl, alkenyl, alkinyl and aryl apply to all substituents of this application. If the (cyclical saturated group) contains heteroatoms, then there are preferably 1 to 3 heteroatoms, in particular 1 or 2 and most preferably one heteroatom, preferably selected from O, S, N, P and B and more preferably from O, S and N. In the formulae (IA) and (lAa) the substituents preferably have the following significance: R,: d-Ce-alkyl; C2-C6-alkenyl; Cz-C6-alkinyl; C4-C16-cycloalkylalkyl, where cycloalkyl is d-do and alkyl is d-d; C5-C16-cycloalkylalkenyl, where cycloalkyl is C3-Ci0 and alkenyl cycloalkylalkinyl, where cycloalkyl is C3-C10 and alkinyl is C2-C6; d-de-arylalkyl, where aryl is C6-C10-aryl and alkyl is Ci-C6-alkyl; d-de-arylalkenyl, where aryl is d-do-aryl and alkenyl IS d~d~ alkenyl; Ca-Ci6-arylalkinyl, where aryl is d-do-aryl and alkinyl is C2-C6-alkinyl; The two substituents Ri can be the same or different; R2: subject to the following definition of X, C,-C5-alkyl; C2-C6-alkenyl; d-d-alkinyl; d-de-cycloalkylalkyl, where cycloalkyl is C3-C10 and alkyl is d-d; C5-C!6-cycloalkylalkenyi, where cycloalkyl is d-do and alkenyl is d-Cel C5-C16-cycloalkylalkinyl, where cycloalkyl is d-do and alkinyl is CrCB; d-de-arylalkyl, where aryl is d-do-aryl and alkyl is Ci-C6-alkyl; d-de-arylalkenyl, where aryl is d-do-aryl and alkenyl is C2-Ca-alkenyl; Cg-CiB-arylalkinyl, where aryl is Ce-Cio-aryl and alkinyl is d-d-alkinyl; d-d-alkanoyl; C3-C6-alkenoyl: C3-Ce-alkinoyl; C7-Cie-arytalkanoyl, where aryl is d-do-aryl and alkanoyl is d-d-alkyl; CB-Ci6-arylalkenoyl, where aryl is Cs-C-to'aryl and alkenoyl is C3-C6-alkenoyl; Cs-C^-arylalkinoyl, where aryl is C6-Ci0-aryl and alkinoyl is C3-Ce_ alkinoyl; R3: hydrogen; d-d-alkyl; d-d-alkenyl; d-de-arylalkyl, where aryf is d-do-aryl and alkyl is d-C6-alkyl; Ca-Ci6-arylalkenyl, where aryl is Ce-C^-aryl and alkenyl is C2-Ce-alkenyl; alkoxyalkyl, where alkoxy is Ci-C6-alkoxy and alkyl is C,-Ce-alkyl; CO^d-Ce-alkyl); C02H; CH2OH. R4: hydrogen; hydroxy; C,-Ce-alkyloxy; C2-C10-alkyloxyalkoxy, where alkyloxy is C,-C4 and alkoxy is d-d-alkyloxy d-d-alkyioxy; C2-C6-alkenyloxy; Crd-alkinyloxy; C4-Ci6-cycloalkylalkyloxy, where cycloalkyl is d-do and aikyl is d-d; C5-C16-cycloalkylalkenyloxy, where cycloalkyl is d-do and alkenyl is d-d; C5-d6-cycloalkylalkinyloxy, where cycloalkyl is d-d0 ar|d alkinyl is d-d; C7-C16- arylalkyloxy. where aryl is C6-C10-aryl and alkyl is d-C6-alkyl; Ca-Cie-arylalkenyloxy, where aryl is C6-C10-aryl and alkenyl is C2-C6-alkenyl; CB-C16-arylalkinyloxy, where aryl is C6-C1D-aryl and alkinyl is C2-C6-alkinyl; Ci-C6-alkanoyloxy; CrCs-alkenoyloxy; C,-C6-alkinoyloxy; C7-C16-arylalkanoyloxy, where aryl is Ce-C^-aryl and alkanoyloxy is C,-C6-alkylanoyloxy; C9-C16-arylalkenoyloxy, where aryl is Ce-Cio-aryl and alkenoyloxy is C3-Ce-alkenoyloxy; C7-C16-arylalkinoyloxy, where aryl is Ca-C10-aryl and alkinoyloxy is C3-C6-alkinoyloxy; Rs: hydrogen; hydroxy; d-C6-alkyloxy; C2-C,0-alkyloxyalkoxy, where alkyloxy is CrC4 and alkoxy is Ci-C6-alkyloxy d-Ce-alkyloxy; CrC6-alkenyloxy; CrC6-alkinyloxy; C4-C16-cycloalkylalkyloxy, where cycloalkyl is C3-C10 and alkyl is 0,-Ce; Cs-C,6-cycloalkylalkenyloxy, where cycloalkyl is C3-C10 and alkenyl is Crd; Cs-Ci6-cycloalkylalkinyloxy, where cycloalkyl is C3-C10 and alkinyl is C2-C6; d-d6-aryialkyloxy, where aryl is C6-C10-aryl and alkyl is d-Cg-alkyl'. C8-Cie-aryialkenyioxy, where aryl is Ce-C^-aryl and alkenyl is C2-CB-alkenyl; Ca-Cie-arylalkinyloxy, where aryl is C6-d0-aryl and alkinyl is C2-C6-alkinyl; C,-Ca-alkanoyloxy; C7-C16-arylalkanoyloxy, where aryl is C6-C10-aryl and alkanoyloxy is d-Ce-alkylanoyloxy; X is oxygen, sulphur or methylene. In this invention alkyl, alkenyl and alkinyl consist of branched or unbranched alkyl, alkenyl and alkinyl. Aryl can be unsubstituted or mono-, di- or trisubstituted independently with hydroxy, halogen, nitro, cyano, thiocyanato, trifluoromethyl, d-C3-alkyl, d-C3-alkoxy, C02H, CONH2, 002(0!-C3-alkyl), CONH(Ci-C3-alkyl), CON(C,-C3-alkyl)2, CO{d-C3-alkyl); amino; (d-Ca-monoalkyl)arnino, (C,-C3- dialkyl)amino; C5-C6-cycloalkylamino; (d-C3-alkanoyl)amido, SH, S03H, S03(Ci-C3-alkyl), S02(Ci- C3-alkyl), SO(d-C3-alkyl), CrC3-alkylthio or C,-C3-alkanoylthio. The above stated definitions for alkyl, alkenyl, alkinyl and aryl apply to all substituents of this application. If the (cyclical saturated group) contains heteroatoms, then there are preferably 1 to 3 heteroatoms, in particular 1 or 2 and most preferably one heteroatom, preferably selected from O, S, N, P and B and more preferably from O, S and N. The compounds of this invention comprise also pharmaceutically and pharmacologically acceptable salts of the compounds of the formula (I). According to this invention both inorganic and also organic salts are suitable. Examples of suitable inorganic salts for this invention are hydrochlorides, hydrobromides, sulphates and phosphates. Possible organic salts are for example methane sulphonates, salicylates, fumarates, maleinates, succinates, aspartates, citrates, oxalates and orotates. In a preferred representation of the formula (I) or (la), when X is oxygen, R, is Ci-C6-alkyl; CrCs-alkenyl; C4-C16- cycloalkylalkyl, where cycloalky! is C3-C10 and alkyl is Ci-C6; C7-C16-arylalkyl, where aryl is C6-aryl and alkyl is Ci-C3-alkyl; R2 is C7-Ci6-arylalkyl, where aryl is C6-Ci0-aryl and alkyl is Cr Ce-alkyl; C8-Ci6-arylalkenyl, where aryl is Ce-Cto-aryl and alkenyl is C2-C6-aikenyl; R3 is hydrogen or methyl; R4 is hydroxy, methoxy or acetoxy. Strongly preferred compounds, in which X is oxygen, are those in which Rt to R4 are as follows (wherein these compounds can be present as free bases / acids or as acceptable salt): Rv methyl, ethyl, propyl, butyl, pentyl, hexyl, in particular methyl, ethyl, propyl and most preferred methyl R2: phenylmethylene (in the examples the notation phenylmethyl is used), phenylethylene, phenylpropylene, phenylbutylene, phenylpentylene, phenylhexylene, whereby the phenyl core can be optionally substituted, in particular phenylpropylene (in the examples this radical is also termed phenylpropyl) R3: methyl, ethyl, propyl, butyl, pentyl, hexyl, in particular methyl, ethyl, propyl and most preferred methyl R4: OH, methoxy, acetoxy, in particular OH One example of a particularly preferred compound is4,5a-epoxy-3-hydroxy-5p,17-dimethyl-143-[(3-phenylpropyl)oxy]morphinan-6-one, in particular the hydrochloride and the hydrobromide. In a particularly preferred representation of this invention the compound is selected from: 17-allyl-4,5a-epoxy-3-methoxy-14p-(3-phenylpropyloxy)morphinan-6-one 17-allyl-4,5a-epoxy-3-hydroxy-14p-{3-phenylpropyioxy)morphinan-6-one 17-allyl-4,5a-epoxy-3-methoxy-53-methyl-14|3-(3-phenylpropyloxy)morphinan-6-one 17-allyl-4,5a-epoxy-3-hydroxy-5(3-methyl-14p-(3-phenylpropyloxy)morphinan-6-one 17-cyclobutylmethyl-4,5a-epoxy-3-methoxy-14p-(3-phenylpropyloxy)morphinan-6-one 17-cyclobutylmethyl-4,5a-epoxy-3-hydroxy-14p-(3-phenylpropyloxy)morphinan-6-one 17-cyclobutylmethyl-4,5a-epoxy-3-methoxy-5p-methyl-143-{3-phenylpropyloxy)morphinan-6-one 17-cyclobutylmethyW,5a-epoxy-3-hydroxy-5P-methyl-14j3-(3-phenylpropyloxy)morphinan-6-one 17-cyclopropylmethyl-4,5a-epoxy-3-methoxy-14p-(3-phenylpropyloxy)morphinan-6HDne 17-cyclopropylmethyl-4,5a-epoxy-3-hydroxy-14p-(3-phenylpropyloxy)morphinan-6-one 17-cyclopropylmethyl-4,5a-epoxy-3-methoxy-5p-methyl-14P-(3-phenylpropyloxy)morphinan-6-one 17-cyclopropylmethyl-4,5a-epoxy-3-hydroxy-5p-methyl-14p-(3-phenylpropyloxy)morphinan-6-one 4,5a-epoxy-3-methoxy-5p,17-dimethyl-14p-[(3-phenylpropyl)oxy]morphinan-6-one 4,5a-epoxy-3-hydroxy-5p117-dimethyl-14p-[(3-phenylpropyl)oxy)]moiphinan-6-one 17-propyl-4,5a-epoxy-3-methoxy-14p-(3-phenylpropyloxy)morphinan-6 17-propyl-4,5a-epoxy-3-hydroxy-14p-(3-phenylpropyloxy)morphinan-6HDne 17-prapyl-4,5a-epoxy-3-methoxy-5p-methyl-14p-(3-phenylpropyloxy)morphinan-6-one 17-prapyl-4,5a-epoxy-3-hydroxy-5p-methyl-14p-(3-phenyipropyloxy}morphinan-6-one 17-tetrahydrofurfuryl-4,5a-epoxy-3-methoxy-14p-{3-phenylpropyloxy)morphinan-6-one 17-tetrahydrofurfufyl-4,5a-epoxy-3-hydroxy-14p-(3-phenylpropyloxy)morphinan-6-one 17-tetrahydrofurfufyl-4,5a-epoxy-3-methoxy-5p-methyl-14p-(3-phenylpropyloxy}morphinan-6-one 17-tetrahydrofurfuryl-4,5a-epoxy-3-hydroxy-5p-methyl-14p-(3-phenylpropyloxy)morphinan-6-one 17-(2-phenylethyl)-4'5a-ePO>fy-3-methoxy-14p-{3-phenylpropyloxy)morphJnan-6 17-(2-phenylethyl)-4,5a-epoxy-3-hydroxy-14p-(3-phenylpropyloxy)morphinan-6-one 17-(2-phenylethyl)-4,5a-epoxy-3-methoxy-5p-rnethyl-14p-{3-phenylpropyloxy)morphinan-6HDne 17-(2-phenylethylH,5a-epoxy-3-hydraxy-5p-methyl-14p-(3-phenylpropylox;y)morphinan-6-one 17-ethyl-4,5a-epoxy-3-methoxy-14p-(3-phenylpropyloxy)morphinan-6-one 17-ethyt-4,5a-epoxy-3-hydroxy-14p-(3-phenylpropyloxy)morphinan-6-one 17-ethyl-4,5a-epoxy-3-methoxy-5p-methyl-14P-(3-phenylpropyloxy)morphinan-6-one 17-ethyl-4,5a-epoxy-3-hydroxy-5p-methyl-14p-(3-phenylprapyloxy)morphinan-6-one 17-cyclopropylmethyl-4,5a-epoxy-3-hydroxy-14P-[(2-methylbenzyl)oxy]morphtnan-6-one 14p-[(2-chlorobenzyl)oxy]-17-(cyclopropylmethyl)-4,5a-epoxy-3-hydroxymorphinan-6-one 14p-benzyloxy-17-cycloprapylmethyl-4,5a-epoxy-3-hydroxymorphinan-6-one 14p-butoxy-17-cyclopropylmethyl-4,5a-epoxy-3-hydroxymorphinan-6-one 17-cyctopropylmethyl-4,5a-epoxy-3-hydroxy-14P-[(3-methylbutyl)oxy]morphinan-6-one 4,5a-epoxy'5p,17-dimethyl-14p-[(3-phenylpropyl)oxy]-3-[(prop-2-inyl)oxy]morphinan-6-one 14p-[(3-chlorobenzyl)oxy]-4,5a-epoxy-17-methyl-3-|(prop-2-inyl)oxy]morphinan-6-one 4,5a-epoxy-17-ethyl-3-methoxy-14p-[(3-phenylpropyl)oxy]morphinan-6-one 4,5a-epoxy-17-ethyl-3-hydroxy-14p-[(3-phenylpropyl)oxy]morphinan-6-one 4,5a-epoxy-3-hydroxy-14p-[(3-methylbutyl)oxy]-17-propylmorphinan-6-one 5P-benzyl-14-methoxycodeinone(=5-benzyl-7,8-didehydro-4,5a-epoxy-3,14p-dimethoxy-17-methyl-morphinan-6-one) 5p-benzyl-4,5a-epoxy-3,143-dimethoxy-17-methylmorphinan-6-one 5p-benzy)-4T5a-epoxy-3-hydoxy-143-methoxy-17-methylmorphinan-6-one ■ 4-hydroxy-3-methoxy-17-methyl-14-[(3-phenylpropyl)oxy]-morphinan-6-one 3,4-dimethoxy-17-methy)-14-[(3-phenylpropyl)oxy]-morphinan-6-one 14p-benzyloxy-4-hydroxy-3-methoxy-17-methylmorphinan-6-one 14p-benzylQxy-3,4-di(inethoxy-17-rfiethylmorphinan-6-one 4-hydroxy-3-methoxy-17-methyl-14P-[(2-naphthylmethyl)oxy]morphinan-6one 3,4-dimethoxy-17-methyl-14(3-[(2-naphthylmethyl)oxy]morphinan-6-one 4-hydroxy-3-methoxy-5p,17Hdimethyl-143-[{3-phenylpropyl)oxy]-morphinan-6-one 3,4-dimethoxy-5p,17-dimethyl-14p-[(3-phenylpropyl)oxy]-morphinan-6-one 14p-ethoxy-4-hydroxy-3-methoxy-5p, 17-dimethylmorphinan-6-one 14p-ethoxy-3,4-dimethoxy-5p,17-dimethylmorphinan-6-one 14P-benzyloxy-3,4-dimethoxy-5p,17-dimethylmorphinan-6-one In a preferred representation of the formula (IA) or (lAa), when X is oxygen, Rt is C,-C6-alkyl, C2-C6-alkenyl, C4-C,a-cycloalkylalkyl, where cycloalkyi is C3-C10 and alkyl is C-pCe, C7-Ci6-arylalkyl, where aryl is C6-aryl and alkyl is CrC3-alkyl; R2 is d-Ce-alkyl, C2-C6-alkenyl, C7-Cie-arylalkyl, where aryl is C6-C10-aryl and alkyl is Ci-C6-alkyl; Ca-C16-arylalkenyl, where aryl is C6-C10-aryl and alkenyl is C2-C6-alkenyl; R3 is hydrogen or methyl; R4 is hydroxy, methoxy or acetoxy. In a particularly preferred representation of this invention is the compound selected from: 4,5a-epoxy-3-hydroxy-17,17-dimethyf-6-oxo-14(3-[(3-phenylpropyl)oxy]morphinanium-iodide (17S)-4,5a-epoxy-17-ethyl-3-hydraxy-17-methyl-6-oxo-14p-[(3-phenylpropyl)oxy]morphinanium-iodide (17RJ-4,5a-epoxy-3-hydroxy-17-methyl-6-oxo-14S-[(3-phenylpropyl)oxy]-17-[(2-R,S-tetrahydrofurfuran-2-yl}methyl]morphinanium-iodide (17R)-17-allyl-4,5a-epoxy-14p-ethQxy-3-hydroxy-17-methyl-6-oxomorphinanium-iodide (17R>-17-allyl-4,5a-epoxy3-hydroxy-14p-methoxy-17-metliyl-6-oxomorphinantum-iodide (17S)-17-allyl-4,5a-epoxy-3-hydroxy-14[3-methoxy-17-methyl-6-oxomorphinanium-iodide 4,5a-epoxy-3-hydroxy-14p-methoxy-17,17-dimethyl-6HDxo-moiphinanium-iodide 5(3-benzyl-143-(butyloxy}-4,5a-epoxy-3-hydroxy-17,17-dimethyl-6-oxomorphinanium-iodide (17S)-17-allyl-5p-benzyl-l4p-butoxy-4,5a-epoxy-3-hydroxy-17-methyl-6-oxomorphinanium-iodide 14p-butoxy-4,5a-epoxy-3-hydroxy-17,17-dimethyl-6-oxomorphinanium-iodide (17R)-17-cyclopropylmethyl-4,5a-epoxy-3-hydroxy-17-methyl-6-oxo-14p-[(3-phenyl propyl )oxy]morphinanium-iodide (17R>-17-cyclopropylmethyl-4,5a-epoxy-3-metrioxy-17-methyl-6-oxo-143-[(3-phenylpropy!)oxy]morphinanium-iodide (17R)-17-cyclopropylmethyl-4,5a-epoxy-3-hydroxy-17-methyl-6-oxo-14p-[(2-phenylbenzyl)oxy]morphinanium-iodide (17R)-14P-[(4-chlorobenzyl)oxy]-17-cyclopropylmethyl-4,5a-epoxy-3-hydroxy-17-methyl-6-oxomorph i nan i u m-iodide 17(R)^,5a-epoxy-3-hydroxy-14P-fTiethoxy-17-methyl-6-oxo-17-(2-phenylethyl)morphinaniurTi-iodide It has now been found that the compounds of the objective invention (morphinan compounds and their quaternary salts substituted in Position 14) represent effective opioid receptor ligands and exhibit a high therapeutic usage potential as analgesics, narcotics, as immunomodulators with immunostimulating or immunosuppressive effects, as cancer therapeutics, inflammation inhibitors, as antirheumatics, for the suppression of organ rejection after transplants, as diuretics, anorectics, as agents against diantioea, obstipation, ileus, pruritis, as anaesthetics or as neuroprotective active substances. The compounds stated in the claims are therefore potentially usable for the treatment of acute and chronic pain, of functional intestinal diseases, such as diarrhoea, abdominal pain, obstipation, ileus, for the treatment of inflammatory intestinal diseases, for the treatment of mammals, especially human beings, for the treatment of the Raynaud syndrome, for the treatment of complaints caused by vasoconstriction, for the treatment of dysmenorrhea, angina pectoris, cardiac infarction, emphysema, bronchial spasms, chronic obstructive bronchitis, rheumatic complaints, oedemas, nephrosis, nephritis in conjunction with rheumatic diseases, for the treatment of tumours, phaeochromocytome, the Addison disease, hepatic cirrhosis, chronic inflammations of the small and large intestines and rectum, for the treatment of pruritis, psoriasis, neurodermatitis, for addition withdrawal from for example opioids, cocaine or alcohol, for the treatment of overweight, or for the treatment of psychic diseases such as dysphoria, depression or schizophrenia. Surprisingly it was also found that the compounds of this objective invention were not capable of overcoming the blood-brain barrier or only to a slight extent, and therefore a special significance could be attributed to them with regard to their use as peripherally effective therapeutics, for example as medicaments for the treatment of pain, for the treatment or prevention of obstipation caused by analgesics, for the treatment or prevention of postoperative ileus, postpartum ileus, for rheumatic therapy, for suppressing organ rejection after transplants with mammals, especially human beings, also for the treatment of erection problems. The limited access to the central nervous system goes with a very reduced side-effect rate, which is relevant to central side effects, such as for example nausea, vomiting, sedation, dizziness, confusion, respiratory depression and mania. Production of the compounds The compounds according to this invention, which are represented by the formula (I) or (la), can be obtained with the aid of the following methods: Starting from thebaine of the formula (ll), this compound is reacted with dialkylsulphates, fluorasu I phonic acid alkylesters, alkylsulphonic acid alkylesters, arylsulphonic acid alkylesters, alkylhalogenides, aralkylhalogenides, alkylsulphonic acid aralkylesters, arylsulphonic acid aralkylesters, arylalkenylhalogenides, chloroformic acid esters or similar compounds in solvents such as tetrahydrofuran, 1,2-dimethoxyethane, diethylether or similar compounds in the presence of a strong base such as n-butyllithium, lithium diethylamide, lithium diisopropylamide or similar compounds at low temperatures (-20°C to -8u"C) (see Boden et al., J. Org. Chem., Vol 47, pp. 1347-1349,1982; Schmidhammer et al., Helv. Chtm. Acta, Vol. 71, pp. 642-647,1988; Gates et al., J. Org. Chem., Vol. 54, pp. 972-975,1984) to obtain the compounds of formula (HI), where R3 is Ct-Cg-alkyl; C2-C6-alkenyl; C7-Cie-arylalkyl, where aryl is C6-C,0-aryl and alkyl is Ci-Ce-alkyl; Cfl-Ci6-arylalkenyl, where aryl is C6-Cio-aryl and alkenyl is C2-C6-alkenyl; alkoxyalkyl, where alkoxy is d-Ce-alkoxy and alkyl is C,-C6-alkyl; COzfd-Ce-alkyl); C02H; CH2OH. The compounds of formula (III) or thebaine (formula (II)) can be converted into the corresponding 14-hydroxycodeinones of formula (IV), where R3 represents hydrogen, d-C6-alkyl; C2-C6-alkenyl; C7-Ci6-arylalkyl, where aryl is C6-C10-aryl and alkyl is Ct-C6-alkyl; C8-Ci6-arylalkenyl, where aryl is C6-C10-aryl and alkenyl is C2-C6-alkenyl; alkoxyalkyl, where alkoxy is CrC6-alkoxy and alkyl is C,-C6-alkyl; CO? (d-Ce-alkyl). This reaction is carried out with performic acid (see H. Schmidhammeretal., Helv. Chim. Acta, Vol. 71,1801-1804, 1988), m-chloroperbenzoic acid or similar at temperatures between 0°C and 60°C. The preferred method is the reaction with performic acid at 0"C to 40°C. These 14-hydroxycodeinones of formula (IV) are reacted in sequence with dialkylsulphates, alkylhalogenides, alkenylhalogenides, alkinylhalogenides, arylalkylhalogenides, arylalkenylhalogenides, arylalkinylhalogenides or chloroformates in solvents such as N,N-dimethylformamide (DMF) ortetrahydrofuran (THF) in the presence of a strong base such as sodium hydride, potassium hydride or sodium amide in order to obtain the compounds of formula (V), where R3 is defined as above; and R2 represents d-Ce-alkyl; C2-C6-alkenyl; C2-C6-alkinyl; C4-C16-cycloalkylalkyl, where cycloalkyl is C3-C10-cycloalkyl and alkyl is d-C6-alkyl; Cs-C16-cycloafkylalkenyl, where cycloalkyl is C3-C10-cycloalkyl and alkenyl is C2-C6-alkenyl; C5-Ci6-cycloalkylalkinyl, where cycloalkyl is C3-C10-cycloalkyl and alkinyl is C2-C6-alkinyl; C7-C16-aryla!ky!, where aryl is C6-C10-aryl and alkyl is Ct-Ce-aikyl; Ca-C18-arylalkenyl, where aryl is C6-C,0-aryl and alkenyl is C2-C6-alkenyl; C8-C16-arylalkinyl, where aryl is C6-C10-aryl and alkinyl is C2-C6-alkinyl; Cr C6-alkanoyl; C3-C6-alkenoyl; C3-C6-alkinoyl; C7-C16-arylalkanoyl, where aryl is Ce-Ci0-aryl and alkanoyl is Ci-C6-alkanoyl; Cg-Ci6-arylalkenoyl, where aryl is C6-C10-aryl and alkenoyl is C3-C6-alkenoyl; CQ-Cia-arylalkinoyl, where aryl is C6-C10-aryl and alkinoyl is C3-C6-alkinoyl. These compounds are then reduced to compounds of formula (VI) using catalytic hydrogenation via a catalyst such as Pd/C, PdO, Pd/Al203, Pt/C, Pt02, Pt/Al203 or similar in solvents such as alcohols, alcohol / water mixtures, glacial acetic acid or similar, where R2 and R3 are defined as above. The following N-demethylation is carried out with chloroformates or bromocyanogens in solvents such as 1,2-dichloromethane, chloroform or similar, and compounds of the formula (VII) are obtained, / where F^ represents C02CH{CI)CH3, C02CH=CH2, C02CH2CCI3, C02CH2CH3, C02Ph, CN or similar; and R2 and R3 are defined as above. The carbamates of formula (VII) are split either by reflux heating in alcohols (in the case of 1-chloroethylcarbamates) or by the addition of hydrogen halogenides or halogens followed by reflux x heating in alcohols (in the case of vinylcarbamates) and the cyanamides of formula (VII) are obtained by acid or alkali hydrolysis, whereby N-Nor compounds of formula (VIII) are obtained, in which R2 and R3 are defined as above. The N-alkylation of the compounds of formula (VIII) is achieved with alkylhalogenides, dialkylsulphates, alkenylhaiogenides, alkinylhalogenides, cycloalkylalkylhalogenides, cycloalkenylalkylhalogenides, arylalkyl halogenides, arylalkenyl halogenides, arylalkinyl halogenides or similar in solvents such as dichloromethane, chloroform or N,N-dimethyiformamide in the presence of a base such as sodium bicarbonate, potassium carbonate, triethylamine or similar and therefore compounds of the formula (IX) are obtained, where R2 and R3 are defined as above; and Rt represents Ci-C6-alkyl; CrC6-alkenyl; Cj-Ce-alkinyl; C4-C,e-cycloalkylalkyl, where cycloalkyl is C3-Ci0-cycloalkyl and alkyl is CVCe-alkyl; C5-C16-cycloalkylalkenyl, where cycloalkyl is C3-CiD-cycloalkyl and alkenyl is C2-C6-alkenyi; C5-C16-cycloalkylalkinyl, where cycloalkyl is C3-C|0-cycloalkyl and alkinyl is C2-C6-alkinyl; C7-C16-arylalky!, where aryl is C6-C10-aryl and alkyl is d-Ce-alkyl; C8-C16-arylalkenyl, whereby aryl is C6-Cio-aryl and alkenyl is C3-C6-alkenyl; Ca-C16-arytalkinyl, where aryl is C6-C10-aryl and alkinyl is CrC6-alkinyl. Ether splitting of these compounds of the formula (IX) with boron tribromide (in a solvent such as dichloromethane or chloroform) at 0eC, 48% hydrobromic acid (reflux heating), with sodium alkanthiolates (in a solvent such as N,N-dimethylformamide) or with other generally well-known ether splitting reagents, gives phenolic compounds of the formula (X), in which R1p R2 and R3 are defined as above. The 3-0 alkylation of the compounds of formula (X) are achieved with alkylhalogenides, dialkylsulphat.es, alkenylhalogenides, alkinylhalogenides, cycloalkylaikylhalogenides, cycloalkylalkenylhalogenides, arylalkylhalogenides, arylalkenylhalogenides, arylalkinylhalogenides or similar in solvents such as dichloromethane, chloroform, acetone or N,N-dimethylformamide in the presence of a base such as sodium bicarbonate, potassium carbonate, triethylamine or similar; 3-0 acylation of the compounds of the formula (X) is achieved with carboxylic acid halogenides, carboxylic acid anhydrides or similar in solvents such as dichloromethane, chloroform, acetone, N,Ni¬di methylformamide, pyridine or similar and therefore compounds of the formula (XI) are obtained; where R1t R2 and R3 are as defined above; R4 represents CVCe-alkyl; C2-C6-alkenyl; C2-C6-alkinyl; C4-C16-cycloa!kylalkyl, where cycloalkyl is C3-C,0-cycloalkyl and alkyl is d-C6-alkyl; C5-C16-cycloalkylalkenyl, where cycloalkyl is C3-C10-cycloalkyl and alkenyl is C2-C6-alkenyl; C5-Cie-cycloalkylalkinyl, where cycloalkyl is C3-C10-cycloalkyl and alkinyl is C2-C6-alkinyl; C7-C16-arylalkyl, where aryl is C6-C10-aryl and alkyl is C^Ce-alky!; CB-C1B-arylalkenyl, where aryl is Cs-C10-aryl and alkenyl is C3-C6-alkenyl; C8-C16-arylalkinyl, where aryl is C6-C10-aryl and alkinyl is CrC6-alkinyl; C,-C6-alkanoyl; 03-C6-alkenoyl; C3-Ce-alkinoyl; C7-C,6-arylalkanoyl, where aryl is C6-C10-aryl and alkanoyl is CrCValkyl; C9-C16-arylalkenoyl, where aryl is C6-C10-aryl and alkenoyl is C3-CValkenoyl; C9-C16-arylalkinoyl, where aryl is C5-C10-aryl and alkinoyl is C3-C6-alkinoyl. An alternative path starts with compounds of formula (XII), in which R, and R3 are defined as above (see Weiss etal., J. Amer. Chem. Soc, Vol. 77, p. 5891, 1955; lijima etal., J. Med. Chern., Vol. 21, pp. 398-400,1978; Coop et al., J. Org. Chem., Vol. 63, pp. 4392-4396, 1998; Schmidharfimer et at., Helv. Chim. Acta, Vol. 71, pp. 1801-1804, 1988; Schmidhammer et al., Helv. Chim. Acta, Vol. 73, pp. 1986-1990, 1990). The ketones of formula (XII) are reacted in the presence of methane sulphonic acid or similar with ethylene glycol (as reagent and solvent) to form the compounds of formula (XIII), in which RT and R3 are defined as above. The introduction of a protective group such as for example benzyl, trityl or silyl to the 3-hydroxy group is achieved by 3-O-benzylation, 3-O-tritylation or 3-O-silylation of the compounds of the formula (XIII) with benzyl halogenides, trityl halogenides, trialkyl halogen silanes in solvents such as dichloromethane, chloroform, acetone or N,N-dimethylformamide in the presence of a base such as sodium bicarbonate, potassium carbonate, triethylamine or similar or by means of phase transfer catalysis and therefore compounds of the formula (XIV) are obtained, where R, and R3 are defined as above; R4 is a protective group such as benzyl, trityl, tri-(Ci-Ca-alkyl)silyl or tri s-(C 7-C, 6 -a ry fa I ky I )s i ly J or another easily split off protective group. These 14-hydroxy compounds are following reacted with dialkylsulphates, alkylhalogenides, alkenylhalogenides, alkinylhalogenides, arylalkylhafogenides, arylalkenylhalogenides, arylalkinyl halogen ides or chloroformates in solvents such as N,N-dimethylformamide (DMF) or tetrahydrofuran (THF) in the presence of a strong base such as sodium hydride, potassium hydride or sodium amide to obtain the compounds of formula (XV), where R1, R2, R3 and R4 are defined as above. If R2and R^are benzyl, compounds of the formula (XIII) can be directly reacted with two equivalents of benzyl bromide in DMF in the presence of sodium hydride, forming 3,14-O-dibenzyl derivatives of the formula (XV), in which R2 and R4 are benzyl and Rt and R3 are defined as above. The acidic splitting of the 3-0 protective group and the ketal function of the compounds with the formula (XV) is earned out in one step with an acid such as hydrochloric acid in methanol, tetrafluoroboric acid in dichloromethane or trifluoroacetic acid and compounds of the formula (X) are obtained (see 1st route). Alternatively to this, if R4 in compounds of formula (XV) is benzyl, one can, through hydragenolysis of the 3-0-benzyl binding with hydrogen gas in the presence of a catalyst such as Pd/C, PdO, Pd/Al203, Pt/C, R02, Pt/Al203 or similar in solvents such as alcohols, alcohol / water mixtures, glacial acetic acid or similar compounds, followed by acid hydrolysis of the ketal function in Position 6 with, for example, methanol and concentrated hydrochloric acid obtain compounds of the formula (X) (see 1SI route). in which R1p R2 and R3 are defined as above. The compounds of the formula (X) are reacted according to the first scheme to form compounds according to the invention of formula (I). Compounds of the formula (l)can be converted to compounds of the formula (la), in which R5 is hydrogen; hydroxy; d-C6-alkyloxy; C2-C10-alkyloxyalkoxy, where alkyloxy is C1-C4 and alkoxy is C,-C6-alkyloxy d-Ce-alkyloxy; CrCB-alkenyloxy; C2-C6-alkinyloxy; C4-C16-cycloalkylalkyloxyt where cycloalkyl is C3-C10 and alkyl is CrC6; C5-C16-cycloalkylalkenyloxy, where cycloalkyl is C3-C10 and alkenyl is C2-C6; C5-Ci6-cycloalkylalkinyloxy, where cycloalkyl is C3-C10 and alkinyl is C2-C6; C7-C16-arylalkyloxy, where aryl is C6-Ci0-aryl and alkyl is Ci-C6-alkyl; C8-Ci6-arylalkenyloxy, where aryl is Ce-Cio-ary' and alkenyl is C2-CB-alkenyl; Ce-Ci6-arylalkinyloxy, where aryl is C6-Ci0-aryl and alkinyl is C2-C6-alkinyl; Ci-C6-alkanoyloxy; C7-C16-arylalkanoyloxy, where aryl is C6-C10-aryl and alkanoyloxy is d-Ce-alkylanoyloxy, as follows: Compounds of the formula (I) can be converted to compounds of the formula (XVI) in that first a reductive opening of the 4,5-ether bridge is carried out with for example zinc in an alcohol, such as methanol or ethanol (preferred temperature 40-80"C) in the presence of ammonium chloride. (Ri, R2 and R3 are as stated above; for R4 see formula (I)) Compounds of the formula (XVI) can be converted to the compounds according to the invention of formula (la) in which R5 is CrCg-alkyloxy; C2-C10-alkyloxyalkoxy, where alkyloxy is C1-C4 and alkoxy is Ci-Ce-alkyloxy d-Ce-alkyloxy; C3-C6-alkenyloxy; C2-C6-alkinyloxy; C4-Ci6-cycloalky(alkyloxy, where cycloalkyl is C3-Ci0 and alkyl is Ci-C6; C5-Cie-cycloalkylalkenyloxy, where cycloalkyl is Cs-C-io and alkenyl is C2-Ce; C5-C16-cycloalky)alkinyloxy, where cycloalkyl is C3-C10 and alkinyl is C2-Ca; C7-CiB-arylalkyloxy, where aryl is Cg-Cio- aryl and alkyl is Ci-Ca-alkyl; C8-C16-arylalkenyloxy, where aryl is C6-C10-aryl and alkenyl is Cz-Ce-alkenyl; Ca-C16-arylalkinyloxy, where aryl is C6-C10-aryi and alkinyl is Cz-Cs-alkinyl; CrC6-alkanoyloxy; C7-Ci6-arylalkanoyloxy, where aryl is C6-C10-aryl and alkanoyloxy is CrCe-alkylanoyloxy, and R1f R2 and R3 are as stated above and R4 is stated in formula (I), through alkylation or acylation according to generally accepted methods. Compounds of the formula (XVI) can be converted to the compounds according to the invention of formula (I) in which R5 is hydrogen by removing the hydroxyl group in Position 4. This can occur for example by the formation of the corresponding phenyltetrazolylether in the presence of a base such as potassium carbonate in a solution such as N,N-dimethylformamide and then catalytic hydration of the phenyltetrazolylether, for example over a catalyst such as Pd/C in an alcohol or glacial acetic acid at temperatures between 20°C and 100°C (see for example Schmidhammer et al. J. Med. Chem. 1984, 27, pp. 1575-1579). Compounds of the formula (I) or (la) can be converted into quaternary ammonium salts of the formula (IA) or (lAa) by alkylation with an appropriate alkyl halogenide or another alkylation agent in solvents such as N,N-dimethylformamide, acetonitrile, acetone, alcohols, tetrahydrofuran, ether, ethyl acetate, etc. or in a solvent mixture. The arrangement of the incoming substituents is preferably axial (see M.A. lorioetal., Eur. J. Med. Chem. - Chim. Ther. 1984,19,301-303). The following examples describe the production of the'compounds according to the invention in detail. Example 1 Synthesis of 17-allyl-4,5a-epoxy-3-methoxy-14p-(3-phenylpropyloxy)morphinan-6-one hypochloride (compound 1 *HCI (Verbindung 1)). Compound 1 NaH (0.97 g, 40.4 mmol) {obtained from 1.62 g 60% NaH dispersion in oil by washing with petroleum ether) was added to a solution of 14-hydroxycodeinone (lijima etal. J. Med. Chem. 1978, 21, pg. 398) (3.00 g, 9.6 mmol) in 100 ml of water-free N,N-dimethy(formamide und N2 at 0°C (bath temperature) under stirring. After 20 min. cinnamyl bromide (2.28 g, 11.6 mmol) is added and the mixture then stirred for 30 min. at 0"C (bath temperature), then stirred further with reducing cooling for 4.5 hours. To terminate the reaction pieces of ice were added until no more hydrogen was produced and the mixture made up to 100 ml of water. The precipitated product was extracted with dichloromethane (3 x 100 ml), the combined organic phases washed with 250 ml saturated sodium chloride solution and dried over sodium sulphate. After removal of the solvent under reduced pressure a brown oil was obtained. This was crystallised from methanol. Yield: 2.49 g (60%) of colourless crystals of 14-cinnamyloxycodeinone (=7,8-dihydro-4,5a-expoxy-3-methoxy-17-methy|-14p-{[{E)-3-phenylprop-2-enyljoxy}mQrphinan-6-one. Fp. 216-219"C; 1H-NMR (DMSO-d6, 5 in ppm): 6 7.46-7.17 (m, 5 arom. H). 7.19 (d, 1 olef. H, CH-8, J = 10.2 Hz), 6.74 (d, 1 arom. H, J = 8.3 Hz), 6.65 (d, 1 arom. H, J = 8.3 Hz), 6.51-6.59 (m, 1 olef. H, -CH=CH-Ph), 6.34 (trans) and 6.26 (cis) (2 ps-d, 1 olef. H, -CH=CH-Ph), 6.18 (d, 1 olef. H, CH-7, J = 10.2 Hz), 4.85 (s, CH-5), 4.26 and 4.11 (2 dxdxd, 2 H, C-14-OCH2-), 3.73 {s, CH30), 2,36 (s, CH3N). A mixture of 14-cinnamyloxycodeinone (6.27 g, 14.6 mmol) and 0.32 g Pd/C (10%) in 200 ml glacial acetic acid was hydrogenated for 3 h at 30 psi and room temperature. The catalyst was filtered off and washed with 50 ml of glacial acetjc acid. The filtrate was evaporated down, water added and alkalised with concentrated ammonia and extracted with dichloromethane (3 x 50 ml). The combined organic phases were washed with saturated sodium chloride solution (3 x 70 ml), dried over sodium sulphate and evaporated down. The oily residue (6.27 g) was crystallised from methanol. Yield: 4.93 g (78%) of colourless crystals of 4.5a^epoxy-3-methoxy-17-methyl-14p-(3-phenylpropyloxy)morphinan-6-one (= 14-0-(3-phenylpropyl)oxycodon). Fp. 119-121'C; 1H-NMR (CDCI3, 6 in ppm): 0 7.35-7.15 (m, 5 arom. H), 6.68 (d, 1 arom. H, J = 8.2 Hz), 6.60 (d, 1 arom. H, J = 8.2 Hz), 4.63 (s, CH-5), 3.89 (s. CH30), 2.34 (s, CH3N). A mixture of 4,5a-epoxy-3-methoxy-17-methyl-14B-(3-phenylpropyloxy)morphinan-6-one (= 14-0-(3-phenylpropyl)oxycodon) (5.00 g, 11.50 mmol), sodium bicarbonate (6.8 g, 80.91 mmol) and chloroformicacid-1-chloroethylester(7.5ml, 67.5 mmol) in 30 ml 1,2-dichloroethane was reflux heated with exclusion of moisture at Q0°C (bath temperature) under stirring. After 17 h filtration was carried out from the inorganic residue, washed with dichloromethane and the filtrate evaporated down. The carbamate produced was not isolated, but rather dissolved in 100 ml methanol and reflux heated for one hour. The solution was evaporated down and the evaporation residue, a colourless foamy resin (6.08 g) was crystallised out of acetone. Yield: 4.91 g (93%) 4,5B-epoxy-3-methoxy-14p-(3-phenylpropyloxy)morphinan-6-one hydrochloride as colourless crystals. Fp. 215-218"C; IR (KBr): 1730 (CO) cm-1; 1H-NMR (CDCI3): 6 10.55 and 8.67 (2 s, wide, 2 H, *KH2), 7.28-7.10 (m, 5 arom. H), 6.75 (d, 1 arom. H, J = 8.2 Hz), 6.71 (d, 1 arom. H, J = 8.2 Hz), 4.41 (s, C5-H), 3.89 (s, CH30); El- MS:m/z419(M*). A mixture of 4,5a-epoxy-3-rnethoxy-14B-{3-phenylpropyloxy)morphinan-6-one hydrochloride (2.00 g, 4.76 mmol), potassium carbonate (4.00 g, 28.9 mmol) and allyl bromide (0.56 ml, 6.62 mmol) in water-free N,N-dimethylformamide(l5 ml) was stirred for 7 h under exclusion of moisture and under nitrogen at 80°C (bath temperature). After filtration from the inorganic residue, which was washed three times each time with 50 ml dichloromethane, the filtrate was evaporated down under reduced pressure. The oily residue was dissolved in 300 ml dichloromethane, washed with water (3 x 200 ml) and saturated sodium chloride solution (4 x 200 ml), dried over sodium sulphate and evaporated down. The obtained brown oil was purified by column chromatography (silica gel; CH2CI2/ MeOH / cone. NR,OH 250 : 2 : 0.5), the oily evaporation residue dissolved in 50 mi ether and precipitated by the addition of etherial HCI up to the acid reaction. The product was recrystallised from isopropanol. Yield: 1.50 g (69%) of the compound 1 .HCI as colourless crystals. Fp. 129-130°C; MS (CI): 460 (Ivf+1); IR (KBr): 1725 (C=0) cm'1; 'H-NMR (DMSO-d6, 5 in ppm): 5 8.98 (s, wide, HN'), 7.30-7.18 (m, 5 arom. H), 6.89 (d. 1 arom. H, J = 8.4 Hz), 6.83 (d, 1 arom. H, J = 8.4 Hz), 5.89 (m, 1 olef. H), 5.69 (m, 2 olef. H), 4.94 (s, CH-5), 3.81 (s, CH30). Example 2 Synthesis of 17-cyclobutylmethyl-4,5a-epoxy-3-methoxy-14p-(3-phenylpropyloxy)morphinan-6-one hydrochloride (compound 2 • HCI). Compound 2 A mixture of 4,5a-epoxy-3-methoxy-14B-(3-phenylpropyloxy)morphinan-6-one hydrochloride (500 mg, 1.19 mmol), potassium carbonate (1.00 g, 7.24 mmol) and cyclobutylmethylbromide (0.6 ml, 5.43 mmol) in water-free N,N-dimethylformamide (7 ml) was stirred for 24 h under exclusion of moisture and under nitrogen at 80"C (bath temperature). After filtration from the inorganic residue, which was washed three times each time with 20 ml dichloromethane, the filtrate was evaporated down under reduced pressure. The oily residue was dissolved in 100 ml dichloromethane, washed with water (3 x 100 mi) and saturated sodium chloride solution (4 x 100 ml), dried over sodium sulphate and evaporated down. The evaporation residue (520 mg of brown oil) was purified by column chromatography (silica gel; CH2CI2/ MeOH /cone. NH4OH 250 : 2 : 0.5), the oily evaporation residue dissolved in 10 ml ether and precipitated by the addition of etherial HCI. Yield: 0.40 g (69%) of the compound 2.HCI as colourless crystals. Fp. 128-133'C; MS (CI): 488 (M*+1); |R (KBr): 1728 (C=0) cm"'; 1H-NMR (DMSO-d6. 5 in ppm): 6 8.48 (s, wide, HN*), 7.30-7.15 (m, 5 arom. H). 6.87 (d, 1 arom. H, J = 8.4 Hz), 6.77 (d, 1 arom. H, J = 8.4 Hz), 4.93 (s, CH-5), 3.81 (s, CH30). Example 3 Synthesis of 17-cyclopropylmethyl-4,5a-epoxy-3-methoxy-143-(3-phenylpropyloxy)morphinan-6-one hydrochloride (compound 3-HCI). Compound 3 A mixture of 4,5a-epoxy-3-methoxy-14B-(3-phenylpropyloxy)morphinan-6-one hydrochloride (1.5 g, 3.57 mmol), potassium carbonate (3.00 g, 21.7 mmol) and cyclopropylmethylbromide (1.0 ml, 6.62 mmol) in water-free N,N-dimethylformamide (10 ml) was stirred for4 h under exclusion of moisture and under nitrogen at 80"C (bath temperature). After filtration from the inorganic residue, which was washed three times each time with 10 ml dichloromethane, the filtrate was evaporated down under reduced pressure. The oily residue was dissolved in 50 ml dichloromethane, washed with water (3 x 50 ml) and saturated sodium chloride solution (4 x 50 ml), dried over sodium sulphate and evaporated down. The evaporation residue (1.42 g of yellow oil) was purified by column chromatography (silica gel; CH2CI2/ MeOH / cone. NH4OH 250 : 2 ; 0.5), the oily evaporation residue dissolved in 50 ml ether and precipitated by the addition of etherial HCI up to the acidic reaction. Yield: 0.60 g (53%) of the compound 3.HCI as colourless crystals. Fp. 130-133°C; MS (El): 473 (M+); IR (KBr): 1725 (C=0) cm-1; 'H-NMR (DMSO-d6, 5 in ppm): 5 8.30 (s, wide, HN+), 7.31-7.18 (m, 5 arom. H), 6.88 (d, 1 arom. H, J = 8.4 Hz), 6.78 (d, 1 arom. H, J = 8.4 Hz), 4.96 (s, CH-5), 3.81 (s, CH30), 0.80-0-40 (m, 5 cyclopropyl H). Example 4 Synthesis of 4,5a-epoxy-3-methoxy-17-(2-phenylethyl)-14p-(3-phenylpropyloxy)morphinan-6-one hydrochloride (compound 4-HCI). Compound 4 A mixture of 4,5a-epoxy-3-methoxy-14B-(3-phenylpropyloxy)morphinan-6-one hydrochloride (1.0 g, 2.38 mmol), potassium carbonate (3.00 g, 21.7 mmol) and 2-phenylethylbromide (1.19 ml, 8.8 mmol) in water-free N,N-dimethylformamide (10 ml) was stirred for 12 h under exclusion of moisture and under nitrogen at 80"C (bath temperature). After filtration from the inorganic residue, which was washed three times each time with 50 ml dichloromethane, the filtrate was evaporated down under reduced pressure. The oily residue was dissolved in 300 ml dichloromethane, washed with water (3 x 200 ml) and saturated sodium chloride solution (4 x 200 ml), dried over sodium sulphate and evaporated down. The evaporation residue (960 mg of brown oil) was purified by column chromatography (silica gel; CH2CI2/ MeOH / cone. NH4OH 250 : 2 : 0.5), the oily evaporation residue dissolved in 50 ml ether and precipitated by the addition of etherial HCI up to the acidic reaction. Yield: 0.45 g (36%) of the compound 4.HCI as colourless crystals. Fp. 128-130°C; MS (CI): 524 (M*+1); |R (KBr): 1726 (C=0) cm-1; 'H-NMR (DMSO-d6, 6 in ppm): 5 8.84 (s, wide, HN*), 7.39-7.17 (m, 10 arom. H), 6.89 (d, 1 arom. H, J = 8.2 Hz). 6.79 (d, 1 arom. H, J = 8.2 Hz), 4.95 (s, CH-5), 3.81 (s, CH30). Example 5 Synthesis of 4,5a-epoxy-17-[2-((R,S)-tetrahydrofuran-2-yl)methyl]-3-methoxy-14B-(3- phenylpropyloxy)morphtnan-6-one hydrochloride (compound 5-HCI). Compound 5 A mixture of 4,5a-epoxy-3-methoxy-14P-(3-phenylpropyloxy)morphinan-6-one hydrochloride (1.0 g, 2.38 mmol), potassium carbonate (0.6 g, 4.34 mmol) and tetrahydrofurfurylchloride (0.5 ml, 4.59 mmol) in water-free N,N-dimethylformamide (10 ml) was stirred for 15 h under exclusion of moisture and under nitrogen at 150°C (bath temperature). The mixture was cooled, 50 ml of water added to it and it was extracted with dichloromethane (3 x 30 ml). The combined organic phases were washed with water (3 x 60 ml) and saturated sodium chloride solution (4 x 100 ml), dried over sodium sulphate and evaporated down. The residue (1.3 g of brown oil) was purified by column chromatography (silica gel; CH2CI2/ MeOH / cone. NH4OH 250 :1.5 : 0.5 -> 250 : 3.5 : 0.5), the oily evaporation residue dissolved in 50 ml ether and precipitated by the addition of etherial HCI up to the acidic reaction. Yield: 0.57 g (48%) of the compound 5.HCI as colourless crystals. Fp. 121-123"C; MS (CI): 504 (M++1); IR (KBr): 1727 (C=0) cm"1; 1H-NMR Example 6 Synthesis of 17-allyM,5a-epoxy-3-hydroxy-14B-(3-phenylpropyloxy)morphinan-6-one hydrochloride {compound 6-HCI). Compound 6 A solution of compound 1.HCI (1.50 g, 3.02 mmol) in 5 ml 48% HBrwas reflux heated for 15 min. Then the solution was cooled, poured onto approx. 50 ml of ice, alkalised with cone. NH4OH and extracted with dichloromethane (3 x 80 ml). The combined organic phases were washed with saturated sodium chloride solution (4 x 50 ml), dried over sodium sulphate and evaporated down. The residue (1.3 g of brown oil) was purified by column chromatography (silica gel; CHJCIJ/ MeOH / cone. NH4OH 250 : 2 : 0.5), the oily evaporation residue dissolved in 50 ml ether and precipitated by the addition of etherial HCI up to the acidic reaction. Yield: 0.5 g (34%) of the compound 6.HCI as colourless crystals. Fp. >250°C (decomp.); MS (CI): 446 (M*+1): IR (KBr): 1725 (C=0)cm"1:1H-NMR (DMSO-de. 5 in ppm): g 9.51 (s, OH), 8.81 (s, wide, HN+), 7.30-7.16 (m, 5 arom. H), 6.71 (d, 1 arom. H, J = 8-0 Hz), 6.64 (d, 1 arom. H. J = 8.0 Hz), 5.92 (m, 1 olef. H), 5.61 (m, 2 olef. H), 4.87 (s, CH-5). Example 7 Synthesis of 17-cyclobutylmethyl-4,5a-epoxy-3-hydroxy-14p-{3-phenylpropyloxy}morphinan-6-one hydrochloride (compound 7-HCI). Compound 7 A solution of compound 2.HCI (336 mg, 0.64 mmol) in 5 ml 48% HBr was reflux heated for 15 min. Then the solution was cooled, poured onto approx. 50 ml of ice, alkalised with cone. NH4OH and extracted with dichloromethane (3 x 50 ml). The combined organic phases were washed with saturated sodium chloride solution (4 x 50 ml), dried over sodium sulphate and evaporated down. The residue (210 mg of brown foamy resin) was purified by column chromatography (silica gel; CH2CI2/ MeOH / cone. NH4OH 250 : 2 : 0.5), the oily evaporation residue dissolved in 50 ml ether and precipitated by the addition of etherial HCI up to the acidic reaction. Yield: 79 mg (34%) of the compound 7.HCI as colourless crystals. Fp. >227°C (decomp.); MS (CI): 474 (M*+1); IR (KBr): 1725 (C=0) cm"1; 1H-NMR (DMSO-d6, 5 in ppm): 6 9.51 (s, OH), 8.30 (s, wide, HN+), 7.29-7.18 (m, 5 arom. H), 6.70 (d, 1 arom. H, J = 8.4 Hz), 6.63 (d, 1 arom. H, J = 8.4 Hz), 4.86 (s, CH-5), Example 8 Synthesis of 17-cyclopropylmethyl-4,5a-epoxy-3-hydroxy-146-(3-phenylpropyloxy)morphinan-6-one hydrochloride (compound 8'HCI). Compound 8 A solution of compound 3.HCI (600 rug, 1.26 mmol) in 5 ml 48% HBrwas reflux heated for 12 min. Then the solution was cooled, poured onto approx. 50 ml of ice, alkalised with cone. NH4OH and extracted with dichloromethane (3 x 50 ml). The combined organic phases were washed with saturated sodium chloride solution (4 x 50 ml), dried over sodium sulphate and evaporated down. The brown oil obtained was purified by column chromatography {silica gel; CH2CI2 / MeOH / cone. NH4OH 250 : 2 : 0.5), the oily evaporation residue dissolved in 50 ml ether and precipitated by the addition of etherial HCI up to the acidic reaction. Recrystallisation out of isopropanol gave 200 mg {34%) of the pure compound 8.HCI as colourless crystals. Fp. 175-178"C; MS (CI): 460 (M*+1); IR (KBr): 1725 (C=0) cm'1; 1H-NMR (DMSO-d6, 5 in ppm): 5 9.52 (s, OH), 8.20 (s. wide, HN*), 7.30-7.18 (m, 5 arom. H), 6.71 {d, 1 arom. H, J = 8.0 Hz), 6.64 (d, 1 arom. H, J = 8.0 Hz), 4.89 (s, CH-5). Example 9 Synthesis of 4,5a-epoxy-3-hydroxy-l7-(2-phenylethyl)-14|3-(3-phenylpropyloxy)morphinan-6-one hydrochloride (compound 9-HCI). Compound 9 A solution of compound 4.HCI (1.79 g, 3.2 mmol) in 5 ml 48% HBrwas reflux heated for 15 min. Then the solution was cooled, poured onto apprax. 50 ml of ice, alkalised with cone. NH4OH and extracted with dichloromethane (3 x 60 ml). The combined organic phases were washed with saturated sodium chloride solution (4 x 60 ml), dried over sodium sulphate and evaporated down. The brown oil obtained (1.02 g) was purified by column chromatography (silica gel; CH2CI2/ MeOH / cone. NH4OH 250 : 2 : 0.5), the oily evaporation residue dissolved in 50 ml ether and precipitated by the addition of etherial HCI up to the acidic reaction. Yield: 247 mg (15%) of the pure compound 9.HCI as colourless crystals. Fp. >218°C (decomp.); MS (CI): 510 (M*+1); 1R (KBr): 1725 (C=0) cm"1; 1H-NMR (DMSO-d6, 6 in ppm): 5 9.51 (s, OH), 8.84 (s, wide, HN+), 7.39-7.17 (m, 10 arom. H), 6.72 (d, 1 arom. H, J = 8.4 Hz), 6.66 (d, 1 arom. H, J = 8.4 Hz), 4.87 (s, CH-5). Example 10 Synthesis of 4,5a-epoxy-17-[2-((R,SHetrahydrofuran-2-yl)methyl]-3-hydroxy-14B-(3- phenylpropyloxy)morphinan-6-one hydrochloride (compound 10-HCI). Compound 10 A solution of compound 5.HCI (600 mg, 1.11 mmol)in 5 ml 48% HBrwas reflux heated for 15 min. Then the solution was cooled, poured onto approx. 50 ml of ice, alkalised with cone. NH40H and extracted with dichloromethane (3 x 60 ml). The combined organic phases were washed with saturated sodium chloride solution (4 x 60 ml), dried over sodium sulphate and evaporated down. The brown oil obtained (0.52 g) was purified by column chromatography (silica gel; CH2CI2/ MeOH / cone. NH4OH 250 : 2 : 0.5), the oily evaporation residue dissolved in 50 ml ether and precipitated by the addition of etherial HCI up to the acidic reaction. Yield: 210 mg (36%) of the compound 10.HCI as colourless crystals. Fp. 170-172X; MS (CI): 490 (M*+1); IR (KBr): 1725 (C=0) cm'1; 1N-NMR {DMSO-de, 5 in ppm): 6 9.45 (s, OH), 8.45 and 7.85 (s. wide, HN+), 7.30-7.21 (m, 5 arom. H), 6.70-6.65 (m, 2 arom. H), 4.90 and 4.87 (2 s, CH-5). Example 11 Synthesis of 4,5a-epoxy-3-hydroxy-143-(3-phenylpropyloxy)-17-propylrnorphinan-6-one hydrochloride (compound 11 • HCI). Compound 11 A mixture of compound 6.HCI (308 mg, 0.64 mmol) and 35 mg 10% Pd/C catalyst in 50 ml methanol was hydrogenated for 3 h at 30 psi and room temperature. The catalyst was filtered off and washed with 50 ml methanol. The filtrate was evaporated down. The evaporation residue, a colourless foamy resin, was dissolved in 30 ml ether and precipitated as the hydrochloride by the addition of etherial HCI up to the acid reaction. Yield: 295 mg (95%) colourless crystals of the compound 11 .HCI. Fp. 162-163X; MS (CI): 460 (M++1); IR (KBr): 1725 (C=0) cm'1; 'H-NMR (DMSO-d6, 5 in ppm): 5 9.51 (s, OH), 8.50 (s, wide. HN*), 7.30-7.18 (m, 5 arom. H), 6.75 (d, 1 arom. H, J = 8.4 Hz), 6.64 {d, 1 arom. H, J = 8.4 Hz), 4.86 (s, CH-5), 0.94 (t, CH3CH2CH2, J = 7 Hz). Example 12 Synthesis of 17-cyclopropylmethyl-4,5a-epoxy-3-hydroxy-14p-[(2-methylbenzyl)oxy]-morphinan-6- one hydrochloride (compound 12.HCI) I Compound 12 A solution of tritylbromide (3.8 g, 11.86 mmol), triethylamine (2.41 ml, 15.99 mmol), DMAP (14 mg, 0.21 mmol) and 17-cyclopropylmethyl-4,5a-epoxy-3,14[3-dihydroxymorphinan-6-spiro-2'-(1,3-dioxolane) (Sen mid hammer et a!., Heterocycles 1998,49, 489-497) (3.0 g, 7.78 mmol) in CH2CI2 (80 ml) was reflux heated for 24 h, cooled and washed with H20 (2 x 100 ml). The combined organic phases were evaporated down and the residue (7.11 g of yellow crystals) was recrystallised out of MeOH (15 ml). Yield: 4.15 g (85%) of 17-cyclopropylmethyl-4,5a-epoxy-14B-hydroxy-3-triphenylmethoxymorphinan-6-spiro-2'-(1,3-dioxolane). Fp. 203-205DC; 1H-NMR (CDCI3) 6 7.50-7.15 (m, 15arom. H), 6.60 (d, 1 arom. H, J =8.2 Hz). 6.30 (d, 1 arom. H, J = 8.2 Hz), 6.13 (s, wide, OH), 4.37 (s, CH-5), 4.12-3.80 (rn, 4H, OCH2CH?0}; CI-MS: m/z 628 (M*+1). NaH (312 mg, 13.34 mmol) (obtained from 520 mg of a 60% NaH dispersion in oil by washing with petroleum ether) was added to a solution of 17-cyclopropylmethyl-4,5a-epoxy-14B-hydroxy-3-triphenylmethoxymorphinan-6-spiro-2'-(1,3-dioxoiane) (2.0 g, 3.18 mmol) in water-free N,N-dimethylformamide (20 ml) under N2 at 0°C (bath temperature) under stirring. After 20 min. 2-methylbenzylbromide (0.64 ml, 5.4 mmol) was added and the resulting mixture stirred for 20 h at room temperature. Excess NaH was broken down by the addition of small pieces of ice and then the mixture was diluted with H20 (80 ml) and extracted with CHZCI2 (1 x 40 ml, 2 x 30 ml). The combined organic phases were washed with H20 (3 x 100 ml), dried (Na2S04) and evaporated down. The residue (1.8 g of orange coloured oil) was purified using column chromatography (silica gel; CH2CI2/ MeOH / cone. NH4OH 250 : 2 : 0.5). 480 mg of a yellow oil was obtained, which was crystallised out of MeOH. Yield: 304 mg (13%) of pure 17-cyclopropylmethyl-4,5a-epoxy-14B-[(2-methylbenzyl)oxy]-3-triphenylmethoxy)morphinan-6-spiro-2"-(1,3-dioxolane). Fp180-182°C; 1H-NMR (Me2SO-d6): 8 7.30-7.15 (m, 19 arom. H), 6.31 (d, 1 arom. H, J = 8.2 Hz), 6.23 (d, 1 arom. H, J =8.2 Hz). 4.68 (d, 1H, OCH2Ar, J = 10.2 Hz), 4.22 (d, 1H, OCH2Ar, J = 10.2 Hz), 4.17 (s, CH-5), 4.05-3.50 (m, 4H, OCH2CH20), 2.33 (s, 3H. MePh); CI-MS: m/z 733 (JvT+1). A solution of 17-cyclopropylmethyl-4,5a-epoxy-14B-[(2-methylbenzyl)oxy]-3-{triphenylmethoxy)mor-phinan-6-spiro-2'-{1,3- Example 13 Synthesis of 14B-[(2-chlorobenzyl)oxy]-17-(cyclopropylmethyl)-4,5a-epoxy-3-hydroxymorphinan-6- one hydrochloride (compound 13.HCI). Compound 13 A mixture of ^-cyclopropylmethyM.Sa-epoxy-S.HB-dihydroxymorphinan-e-spiro-^-tl.S-dioxolane) (Schmidhammeretal. Heterocycles 1998, 49, 489-497) (6.9 g, 17.9 mmol), K2C03 (6.7 g, 48.48 mmol), benzyibromide (2.34 ml, 19.66 mmol) and water-free N,N-dimethylformamide (70 ml) was stirred for 22 h under N2 and at room temperature. The inorganic material was filtered off and the filtrate evaporated down. The residue was dissolved in CH2CI2 (80 ml), washed with H20 (7 x 50 ml), dried over Na2S04 and evaporated down. The residue (8.2 g of colourless crystals) was recrystallised out of MeOH. Yield: 7.37 g (87%) 3-benzyloxy-17-cyclopropylmethyl-4,5a-epoxy-14f-hydroxymorphinan-6-spiro-2'-(1,3-dioxolane). Fp. 130-1318C; 1H-NMR (CDCI3): 5 7.42-7.27 (m, 5 arom. H), 6.75 (d, 1 arom. H. J = 8.3 Hz). 6.54 (d, 1 arom. H, J = 8.3 Hz), 5.17 (d, 1H, OCH2Ph, J = • 11.7 Hz), 5.10 (d, 1H, OCH2Ph, J = 11.7 Hz), 4.58 (s, C-5H), 4.19-3.73 (m, 4H, OCH2CH20); CI-MS: nVz476(M*+i). A mixture of 3-(benzyloxy)-17-(cyclopropylmethyl)-4,5a-epoxy-l43-hydroxy-morphinan-6-spiro-2'-(1,3-dioxolane) (5.82 g, 12.2 mmol), NaH {1.47 g, 61.3 mmol; obtained from 2.45 g of a 60% NaH dispersion in oil by washing with petroleum ether) and 100 ml water-free N,N-dimethylformamide was stirred for 25 min. under N2 at 0-5°C (bath temperature). 2-chlorobenzylbromide (3.16 ml, 24.3 mmol) was added and the resulting mixture stirred for4 h (1 h at 0-5°C, 3 h at room temperature). Excess NaH was broken down by the addition of small pieces of ice, and then the mixture diluted with H20 (350 ml) and extracted with CH2CI2 (1 x 250 ml, 3 x 100 ml). The combined organic phases were washed with H20 (3 x 100 ml) and saturated sodium chloride solution (2 x 50 ml), dried (Na2S04), and evaporated down. The residue (8.3 g of yellowish oil) was purified using column chromatography (silica gel; CH2CI2/ MeOH / cone. NH4OH 250 :4 : 0.5). 4.75 g (65%) of pure 3-(benzyloxy)-143-[(2-chlorobenzyl)oxy3-17-cyclopropylmethyl-4,5a-epoxymorphinan-6-spiro-2'-(1,3-dioxolane) was obtained as a colourless oil, which was used for the next synthetic stage as such. 1H-NMR (Me2SO-d6) 5 7.71-7.31 (m, 9 arom. H), 6.79 (d, 1 arom. H, J = 8.0 Hz), 6.57 (d, 1 arom. H, J = 8.0 Hz), 5.14 (d, 1H, OCH2Ar, J = 11.6 Hz), 5.07 (d, 1H, OCH2Ar, J= 11.6 Hz), 4.81 (d, 1H, OCH2Ar, J = 12 Hz), 4.50 (s, C5-H), 4.46 (d, 1H, OCH2Ar, J = 12 Hz), 4.01-3.74 (m, 4H, OCH2CH20). A solution of 3-benzyloxy-14p-[(2-chlorobenzyl)oxy]-17-cyclopropylmethyl-4,5a-epoxymorphinan-6-spiro-2"-{1,3-dioxolane)(5.50g, 9.16 mmol) in MeOH (52 ml) and cone. HCI (23 ml) was reflux heated for 2.5 h. After cooling with ice, the solution was afkalised with cone. NH4OH and extracted with CH2CI2 (1 x 200 ml, 1 x 100 ml, 2 x 50 ml). The combined organic phases were washed with H20, dried over Na2S04 and evaporated down. The residue (5.54 g of yellowish oil) was purified using column chromatography (silica gel; CH2CI2 / MeOH / cone. NH4OH 250 : 3 : 0.5) and in this way 2.69 g (63%) of pure 14[3-[(2-chlorobenzyl)oxy]-17-cyclopropylmethyl)-4,5a-epoxy-3-hydroxymorphinan-6-one (compound 13) was obtained. A part was dissolved in ether and etherial HCI added to it. Compound 13.HCI was isolated. Fp. 165-168°C; 'H-NMR (Me2SO-d6) 5 8.63 (br. s, OH), 7.96 (s, 1H, *NH), 7.50-7.30 (m. 4 arom. H), 6.74 (d, 1 arom. H, J = 8 Hz), 6.69 (d, 1 arom. H, J = 8 Hz), 5.19(s, Cs-H). 4.87 (d, 1H,0CH2Ar, J = 11.6 Hz), 4.81 (d, 1H, OCH2Ar, J = 11.6 Hz); CI-MS: m/z466(M*+1). Example 14 Synthesis of 143-benzyloxy-17-cyclopropylmethyl-4,5a-epoxy-3-hydfoxymorphinan-6-one (compound 14.HBr). Compound 14 A solution of 3,146-dibenzyloxy-17-cyclopropylmethyl-4,5a-epoxymorphinan-6-spiro-2'-(1,3-dioxolane)(Schmidhammeretal., Heterocycles 1998,49,489-497) (10.0 g, 17.68 mmol) in MeOH (200 ml) / H20 (250 ml) / cone. HCI (50 ml) was reflux heated for 4 h. After cooling with ice, the solution was alkalised with cone. NH4OH and extracted with CH2CI2 (1 x 100 ml, 2 x 25 ml). The combined organic phases were washed with H20, dried over Na2S04 and evaporated down. The residue (8.48 g of slightly brown foamy resin) was purified using column chromatography (silica gel; CH2Cl2/MeOH/cone. NH4OH 90: 9: 1) and in this way 6.28 g of 3,14p-dibenzyloxy-17-cyclopropylmethyl-4,5a-epoxymorphinan-6-one (Schmidhammer et al., Heterocycles 1998,49, 489-497) was obtained as colourless foamy resin and 1.14 g (18%) of the compound 14 as a slightly yellow foamy resin. One part of the compound 14 was converted in the usual way to the hydrobromide (compound 14.HBr) using 48% HBr. Fp. >210°C (decomp.); 1H-NMR (Me2SO-dB) 5 9.48 (s, OH), 8.31 (s, *NH), 7.56-7.32 (m, 5 arom. H), 6.72 (d, 1 arom. H, J = 8 Hz), 6.68 (d, 1 arom. H, J = 8 Hz), 5.10 (s, C-5 H), 4.70 (d, 1H. OCH2Ph, J = 10.4 Hz), 4.25 (d, 1H, OCH2Ph, J = 10.4 Hz); CI-MS:m/z432(M++1). Example 15 Synthesis of 14B-butoxy-17-cyclopropylmethyl-4,5a-epoxy-3-hydroxymorphinan-6-one hydrochloride (compound 15-HCI). Compound 15 NaH (2.8 g, 118 mmol; obtained from 4.2 g of a 60% NaH dispersion by washing with petroleum ether) was added to an ice-cooled, stirred solution of 3-benzyloxy-17-cyclopropylmethyl-4,5a-epoxy-14p-hydroxymorphinan-6-spiro-2'-(1,3-dioxolane) (see Example 13) (10.70 g, 22.5 mmol) in 200 ml water-free N,N-dimethylformamide under N2. After 15 min. trans-crotylbromide (27 mmol, 3.2 ml of an 85% trans-crotylbromide solution) was added and stirred for 3.5 h (1 h at 0-5°C, 2.5 h at room temperature). After the breakdown of excess NaH by the addition of small pieces of ice, the mixture was poured onto 500 ml H2O and extracted with CH2CI2 (3 x 100 ml, 2 x 50 ml). The combined organic phases were washed with H20 (3 x 200 ml) and saturated NaCI solution, dried over Na2S04 and evaporated down. The residue from the evaporation (13.85 g of yellow oil) was purified using column chromatography {silica gel; CH2CI2/ MeOH / cone. NH4OH (250 / 3 / 0.5)). The residue from the evaporation (7.11 g of yellow oil) was dissolved in ether and 3-benzyloxy-14B-[(E)-{but-2enyl)oxy]-l7-cyclopropylmethyl-4,5a-epoxymorphinan-6-spiro-2'-(1,3-dioxolane)was precipitated as the hydrochloride by the addition of etherial HCI. Yield: 6.85 g (54%). Fp. 135-139°C; 'H-NMR (DMSO-de): 5 8.11 (s, wide, 'NH), 7.50-7.25 (m, 5 arom. H), 6.92 (d, 1 arom. H, J = 8.4 Hz), 6.68 (d, 1 arom. H, J = 8.4 Hz), 5.79 (m, 2 olefin. H), 5.14 (s, 2 H, C3OCHz), 4.59 (s, Cs-H), 4.20-3.72 (m, 6 H, C6-(OCH2}2, C14(OCH2), 1.72 (m, 3 H, CH=CHCHj); MS (CI): m/z 530 (M*+1). A mixture of 3-benzyloxy-14|3-[(E)-(but-2-enyl)oxy]-17-cyclopropylmethyl-4,5a-epoxymorphinan-6-spiro-2'-(1,3-dioxolane) hydrochloride (6.27 g, 11 mmol), 630 mg of 10% Pd/C catalyst and 100 ml MeOH was hydrogenated for 2 h at room temperature and 30 psi. Then the catalyst was filtered off and the filtrate was evaporated down in a vacuum. The evaporation residue (reddish crystals) was treated with reflux boiling MeOH. Yield: 4.17 g (79%) of colourless crystals of 14B-butoxy-17-cyclopropylmethyl-4,5a-epoxy-3-hydroxymorphinan-6-spiro-2'-(1,3-dioxolane) hydrochloride. Fp. 247-252°C; 1H-NMR (DMSO-d6): a 9.23 (s, 1 H, OH), 7.87 (s, wide, 1 H, *NH), 6.68 (d. 1 arom. H, J = 8.2 Hz), 6.57 (d, 1 arom. H, J = 8.2 Hz), 4.49 (s, C5-H), 4.11-3.55 (m, 4H, C6(OCH2)2), 0.95 (t, 3 H, CH2CH3, J = 7.4 Hz); MS (CI): m/z 443 (M*+1). A solution of 14p-butoxy-17-cyclopropylmethyl-4,5a-epoxy-3-hydroxymorphinan-6-spiro-2'-(1,3-dioxolane) hydrochloride(4.07 g, 8.5 mmol)in 100 ml MeOH/H20/cone. HCI (50 : 85 :15)was reflux heated for 4 h. After the addition of H20 (70 ml) and alkalisation with cone. NH4OH extraction with CH2CI2 (3 x 60 ml) occurred. The combined organic phases were washed with H20 and saturated NaCI solution, dried over Na2SO« and evaporated down. The evaporation residue (3.63 g of brown oil) was purified using column chromatography (silica gel; CH2CI2/ MeOH / cone. NH4OH 250 : 3.5 : 0.5)). One part of the evaporation residue (2.71 g of colourless foamy resin, 80%) was dissolved in ether and the compound 15-HCI (2.46 g) was obtained as a pure substance by the addition of etherial HCI. Fp. 240°C (decomp.); IR (KBr): 1725 (CO) cm'1; 1H-NMR (DMSO-d6): 5 9.50 (s, OH). 8.15 (s, wide, *NH), 6.71 (d, 1 arom. H, J = 8.0 Hz). 6.65 (d, 1 arom. H, J = 8.0 Hz), 4.93 (s, Cg-H), 0.95 (t, 3 H, CH2CH3, J = 7.2 Hz); MS (CI): m/z 399 Example 16 Synthesis of 17-cyclopropylmethyl-4,5a-epoxy-3-hydroxy-14p-[(3-methylbutyl)oxy]morphinan-6-one hydrochloride (compound 16-HCI). Compound 16 NaH (840 mg, 35 mmol; obtained from 1.4 g of a 60% NaH dispersion by washing with petroleum ether) was added to an ice-cooled, stirred solution of 3-benzyloxy-17-cyclopropylmethyl-4,5a-epoxy-14P-hydroxymorphinan-6-spiro-2'- The oil obtained was dissolved in ether and 3-benzyloxy-17-cyclopropylmethyl-4,5a-epoxy-14B-[(3-methylbut^-enyljoxyjmorphinan-e-spiro^'-tl ,3-dioxolane) hydrochloride was obtained as a pure substance by the addition of etherial HCI. Yield: 3.81 g (78%). Fp.l26-129°C; 1H-NMR (DMSO-d8)-. & 8.15 (s, wide, *NH), 7.45-7.25 (m, 5 arom. H), 6.92 (d, 1 arom. H, J = 8.0 Hz), 6.68 (d, 1 arom. H, J = 8.0 Hz), 5.51 (m, 1 olefin. H), 5.14 (s, 2H, C3OCH2), 4.58 (s, C5-H), 3.92-3.44 (m, 4 H, Cs(OCH2)2), 1.76 (s, 3H, CH^CCHj); 1.67 (s, 3 H, CH=CCH3); MS (CI): m/z 544 (M++1). A mixture of 3-benzyloxy-17-cyclopropylmethyl-4,5a-epoxy-14p-[(3-methylbut-2-enyl)oxy]-morphinan-6-spiro-2'-(1,3-dioxolane) hydrochloride (4.01 g, 6.9 mmol), 400 mg of 10% Pd/C catalyst and 100 ml MeOH was hydrogenated for 2.5 h at room temperature and 30 psi. Then the catalyst was filtered off and the filtrate was evaporated down. The evaporation residue was treated with ether, the insoluble portion filtered off, and etherial HCI added to the filtrate and in this way 17- cyclopropylmethyl-4,5a-epoxy-3-hydroxy-140-[(3-methy!buty!)oxy]morphinan-6-spiro-2'-(1,3-dioxolane) hydrochloride was obtained as a pure substance. Yield: 2.24 g (66%). Fp. 191-193°C; 1H-NMR (DMSO-d6): o" 9.22 (s, OH), 7.83 (s, wide, +NH), 6.69 (d, 1 arom. H, J = 8.0 Hz), 6.58 (d, 1 aram. H, J = 8.0 Hz), 4.47 (s, C5-H), 4.08-3.50 (m, 4H, CB(OCH2)2). 0-96 (d, 3 H, CHCtb, J = 4.8 Hz); 0.92 (d, 3 H, CHCHa, J = 4.8 Hz); MS (CI): mte 457 (M*+1). A solution of 17-cyc(opropy(methyl-4,5a-epoxy-3-hydroxy-14p-[{3-methyl-bijtyl)oxy]morphinan-6- spiro-2*-(1,3-dioxolane) hydrochloride (2'.8 g, 5.7 mmol) in 110 ml MeOH / H20 / cone. HCI (4 : 5 :1) was reflux heated for 4.5 h. After the addition of H20 (80 ml) and alkalisation with cone. NH»OH extraction with CHjCb (1 x 80 ml, 3 x 50 ml) occurred. The combined organic phases were washed with H20 and saturated NaCI solution, dried over Na2S04 and evaporated down. The evaporation residue (2.5 g of brown oil) was purified using column chromatography (silica gel; CH2CI2/ MeOH / cone. NH4OH 250 : 3: 0.5)). The evaporation residue (2.21 g of white foamy resin) was dissolved in ether and the compound 16'HCI was obtained as a pure substance by the addition of etherial HCI. Yield: 1.99 g (78%). Fp. 168-170°C; IR (KBr): 1725 (CO) cm-'; 'H-NMR (OMSO-d6): 6 9.50 (s, OH), ' 8.08 (s, wide, *NH), 6.72 (d, 1 arom. H, J = 8.0 Hz), 6.66 (d, 1 arom. H, J = 8.0 Hz), 4.92 (s, C5-H), 0.96 (d, 3 H, CHCH3, J = 3.8 Hz); 0.93 (d, 3 H, CHCH3, J = 3.8 Hz); MS (CI): m/z 412 (M*+1). Example 17 Synthesis of 4,5a-epoxy-5g,17^imethyl-Hp-[(3^henyipropyi)oxy]-3-[(prop-2Hnyi)oxy]mcTphinari-6-one hydrochloride (compound 17.HCI). NaH (0.72 g, 30.0 mmol; obtained from 1.2 g of a 60% NaH dispersion in oil by washing with petroleum ether) was added to a solution of 14-hydroxy-5-methlycodeinone (Schmidhammer et al., Helv. Chim. Acta, 1988, 73, p. 642} (5.00 g, 15.27 mmol) in 30 ml water-free N,N-dimethylforrnamide under Nz at 0°C (bath temperature) under stirring. After 25 min. a solution of cinnamyl bromide (3.01 g, 15.27 mmol) in 20 ml N,N-dimethylformamide was added drop by drop and the mixture stirred for 1.5 h at 0"C (bath temperature). Small pieces of ice were added until no more hydrogen was produced, the mixture was poured onto 500 ml H;0 and extracted with dichloromethane/isopropanol (4:1) (1 x 150 ml, 3 x 50 ml). The combined organic phases were washed with H20 (5 x 400 ml) and 1 x with 250 ml saturated sodium chloride solution, dried over sodium sulphate and evaporated down. The evaporation residue (7.59 g of orange coloured oil) was crystallised out of isopropanol/ether(1:1) (20 ml). Yield: 3.03 g (45%) of colourless crystals of 14-cinnamyloxy-5-methylcodeinone (= 7,8-didehydro-4,5a-epoxy-3-methoxy-5G,l7-dimethyl-14B-{[(E/Z)-3-phenylprop-2-enyl]axy}morphinan-6-one). Fp. >150°C (decomp.); IR (KBr): 1675 (CO)cm'1; 1H-NMR (DMSO-d6> 6 in ppm): 5 7.44-7.23 (m, 5 arom. H, 1 olef. H), 6.70 (d, 1 arom. H, J = 8.2 Hz), 6.62 (d, 1 arom. H, J = 8.2 Hz), 6.56 (d, 1 olefin. H, -CH=CH-Ph, J = 15.7 Hz)), 6.33 (dt, 1 olef. H, -CH=CH-Ph, J = 15.7 Hz), 6.10 (d, 1 olef. H, J = 10.0 Hz), 4.26 and 4.11 (2 dd, 2 H, C-14-OCHr, J = 5.0 and 10.6 Hz), 3.70 (s, CH30), 2.36 (s, CH3N), 1.61 (s, C5-CH3); CI-MS: m/z 444 (M*+1). A mixture of 14-cinnamyloxy-5-methylcodeinone (3.44 g, 7.76 mmol), 10% Pd/C catalyst (350 mg) and 80 ml EtOH was hydrogenated for 2 h at a temperature of 50"C and 50 psi. Then the catalyst was filtered off, the filtrate was evaporated down and the residue (3.31 g of dark oil) was crystallised out of 10 ml EtOH. Yield: 2.52 g (73%) of 4,5a-epoxy-3-methoxy-5B,17-dimethyl-14B-{(3-phenylpropyl)oxy]morphinan-6-one (compound 17a). Fp. 126-128°C; IR (KBr): 1720 (CO) cm"1; 1H-NMR (CDCI3, 5 in ppm): 5 7.32-7.17 (m, 5 arom. H), 6.67 (d, 1 arom. H, J = 8.2 Hz), 6.58 (d, 1 arom. H, J = 8.2 Hz), 3.87 (s, CH30), 2.34 (s, CH3N), 1.65 (s, C5-CH3); CI-MS: m/z 448 (M*+1). A solution of 4,5a-epoxy-3-methoxy-5B,17-dimethyl-143-[(3-phenylpropyl)oxy]morphinan-6-one (2.23 g, 4.98 mmol) in 13 ml 48% HBr was reflux heated for 20 min, then cooled and evaporated down. The evaporation residue was dissolved in 20 ml MeOH and evaporated down. The process was repeated 1 x, whereby 2.48 g of beige crystals were obtained, which were recrystallisedoutof 15 ml MeOH. Yield: 2.26 g (88%) 4.5a-epaxy-3-hydroxy-5B,17-dimethyl-14B-[(3-phenylpropyl)oxy]morphinan-6-one hydrobromide (compound 17b.HBr). Fp. >270"C (decomp.); IR (KBr): 1720 (COJcm-1; 1H-NMR (DMSO-d6, 6 in ppm): 6 9.42 (s, OH), 8.58 (s, *NH), 7.36-7.16 (m, 5 arom. H), 6.69 (d, 1 arom. H, J = 8.2 Hz), 6.64 (d, 1 atom. H, J = 8.2 Hz), 2.97 (s, CH3N), 1,65 (s, C5-CH3); CI-MS: m/z 434 (M*+1). A mixture of 4,5a-epoxy-3-hydroxy-5(3,17Hdimethyl-14p-[(3-phenylpropyl)oxy]morphinan-6-one hydrobromide (380 mg, 0.88 mmol), calcium carbonate {370 mg, 2.68 mmol), propargylbromide (0.20 ml, 2.66 mmol) and 25 ml acetone was reflux heated under N2 for 7 h. The inorganic material was filtered off, the filtrate evaporated down and the residue (460 mg of orange coloured oil) was purified using column chromatography (silica gel; CH2CI2/MeOH/cone. NH4OH 250 : 2 : 0.5). The evaporation residue (350 mg of yellow oil) was dissolved in ether and etherial HCI was added to it, whereby 220 mg (49%) of the compound 17.HCI was obtained. Fp. > 130-1338C; IR (KBr): 1727 (CO) cm"1; ^-NMR (DMSO-d6, 5 in ppm): 6 9.38 (s, *NH), 7.34-7.19 (m, 5 arom. H). 6.92 (d, 1 arom. H, J = 8.4 Hz), 6.78 (d, 1 arom. H, J = 8.4 Hz), 4.81 (d, 2H, HCCChfeO-CS, J = 1 Hz), 3.59 (d, 1 H, HCCCH20-C3, J = 1 Hz), 2.94 (s, CH3N), 1.53 (s, C5-CH3); CI-MS: m/z 472 (M*+1). Example 18 Synthesis of 14p-[(3-chlorobenzyl)oxy]-4,5a-epoxy-17-methyl-3-[(prop-2-inyl)oxy]-morphinan-6-one hydrochloride (18-HCI). Compound 18 NaH (1.60 g, 66.76 mmol; obtained from 2.67 g of a 60% NaH dispersion by washing with petroleum ether) was added to a solution of 4,5a-epoxy-14B-hydroxy-3-methoxy-17-methylmorphinan-6-spiro-2"-(1,3-dioxolane) (Lester et al., Tetrahedron 1965, 21. pp. 771-778) (6.00 g, 16.69 mmol) in 100 ml water-free N,N-dimethylformamide under N2 at 0"C (bath temperature) under stirring. After 15 min. 3-chlorobenzylbromide (4.4 ml, 33.38 mmol) was added and stirred for 24 h (1 h at 0-5"C, 23 h at room temperature). After the breakdown of excess NaH by adding small pieces of ice, the mixture was poured onto 300 ml H20 and extracted with CH2CIZ (1 x 100 ml, 3 x 40 ml). The combined organic phases were washed with H20 (4 x 200 ml) and saturated NaCI solution, dried over Na2S04 and evaporated down. The evaporation residue (13.36 g of yellow oil) was crystallised out of MeOH and recrystallised. Yield: 4.29 g (53%) of 14p-[(3-chlorobenzyl)oxy]-4,5a-epoxy-3-methoxy-17-methylmorphinan-6-spiro-2'-(1,3-dioxolane) as colourless crystals. Fp. 131-133"C; ^-NMR (DMSO-d6): 5 7.58-7.26 (m, 4 arom. H), 6.74 (d, 1 arom. H, J = 8.1 Hz), 6.60 (d, 1 arom. H, J = 8.1 Hz), 4.55 (d, 1H, CuOCH2l J = 11.8 Hz), 4,31 (d, 1H, CuOCH2, J = 11.8 Hz), 4.42 (s, C5-H), 4.10-3.61 (m, 4H, C6(OCH2)2), 3.78 (s, OCH3), 2.30 (s, NCH3); MS (CI): m/z485 (M*+1). A mixture of 14p-[(3-chlorobenzyl)oxy]-4,5a-epoxy-3-methoxy-17-methylmorphinan-6-spiro-2'-(1,3-dioxolane) (3.00 g, 6.2 mmol), sodium ethane thiolate (2.32 g, 27.6 mmol) and 30 ml of water-free N,N-dimethylformamide was stirred for 5 h under N2 at 130°C (bath temperature) and then poured onto 400 ml H20 and extracted with CH2CI2 (1 x 100 ml, 3 x 60 ml). The combined organic phases were washed with H20 (4 x 200 ml) and saturated NaCI solution, dried over Na2S04 and evaporated down. The evaporation residue (3.36 g of dark brown oil 14|3-[(3-chJorobenzyl)oxy]-4,5o>epoxy-3-hydroxy-17-methylmorphinan-6-spiro-2'-(1,3-dioxolane)) could not be crystallised. Therefore one part (2.8 g) was used without further purification for representing 14B-[(3-chlorobenzyl)oxy]-4,5a-epoxy-3-hydroxy-17-methylmarphinan-6-one. The remainder (414 mg) was purified using column chromatography (silica gel; CH2CI2/ MeOH / cone. NH4OH (250 : 2 : 0.5)). The evaporation residue (352 mg of yellow oil} was dissolved in ether and 143-[(3-chlorobenzyl)oxy]-4,5a-epoxy-3-hydroxy-17-methylmorphinan-6-spiro-2'-(1,3-dioxolane) hydrochloride (250 mg)was precipitated as a pure substance by the addition of etherial HCI. Fp. 202-205°C; 'H-NMR (DMSO-d6): 6 9.28 (s, OH), 8.92 (s, wide, *NH), 7.60-7.36 (m, 4 arom. H), 6.70 (d, 1 arom. H, J = 8.2 Hz), 6.60 (d, 1 arom. H, J = 8.2 Hz), 4.59 (s, C5-H), 4.76 (d, 1H, Ci4OCH2, J = 11.9 Hz), 4.57 (d, 1 H, C14OCH2, J = 11.9 Hz), 4.11-3.61 (m, 4H, C6(OCH2)2), 2.88 (d, +NCH3, J = 4.6 Hz); MS (CI): m/z471 (M++1). A solution of unpurified 14(3-[(3-chlorobenzyl)oxy]-4,5a-epoxy-3-hydroxy-17-methylmorphinan-6-spiro-2'-(1,3-dioxolane) (2.8 g of dark brown oil) in 100 ml MeOH / H20 / cone. HCI (4 : 5 :1) was reflux heated for 7 h. After the addition of ice-water and alkalisation with cone. NH4OH extraction took place with CH2CI2 (3 x 60 ml). The combined organic phases were washed with H20 (3 x 100 ml) and saturated NaCI solution, dried over Na2S04 and evaporated down. From the evaporation residue (1.94 g of brown foamy resin 14B-[(3-chtorobenzyl)oxy]-4,5a-epoxy-3-hydroxy-17-methyl-morphinan-6-one) one part (1.50 g) was used for further syntheses without further purification. The remainder (443 mg) was purified using column chromatography (silica gel; CH2CI2/ MeOH/cone. NH4OH (250 :4 : 0.5)). The evaporation residue (353 mg of yellow foamy resin) was dissolved in ether and 14B-[(3-chlorobenzyl)oxy]-4,5a-epoxy-3-hydroxy-17-methylmorphinan-6-one hydrochloride (335 mg) was precipitated as a pure substance by the addition of etherial HCI. Fp. 205-210"C; IR (KBr): 1724 (CO) cm"1; 1H-NMR (DMSO-d6): 0 9.55 (s, OH), 9.15 (s, wide, +NH), 7.70-7.25 (m, 4 arom. H), 6.73 (d, 1 aram. H, J = 8 Hz), 6.67 (d, 1 arom. H, J = 8 Hz), 5.10 (s, C5-H), 4.87 (d, 1H, OCH2), J = 12.4 Hz), 4.68 (d, 1 H, 0CH2), J = 12.4 Hz), 2.93 (d, +NCH3, J = 4.6 Hz); MS (CI): m/z 427 (M++1). A mixture Of unpurified 14B-[(3-chlorobenzyl)oxy]-4I5a-epoxy-3-hydroxy-17-metriylmorphinan-6-one {500 mg of brown foamy resin), K2C03 (485 mg, 3.51 mmol) and propargylbromide (0.26 ml, 3.51 mmol) and 40 ml acetone (with 0.5% H20) was reflux heated under N2 for 3 h. After cooling the inorganic material was filtered off, washed with CH2CI2 and the filtrate evaporated down. The evaporation residue (538 mg of brown oil) was purified using column chromatography (silica gel; CH2Cl2/ MeOH / cone. NH4OH (250 : 2 : 0.5)). The evaporation residue (337 mg of yellow oil) was dissolved in ether and 18-HCI was precipitated as a pure substance by the addition ofetherial HCI. Yield: 347 mg (74%). Fp. 145-150'C; IR (KBr): 1717 (CO), 2118 (C=C) cm-'; 1H-NMR (DMSO-d6): 6 9.21 (s, wide, +NH), 7.71-7.32 (m, 4 arom. H), 6.96 (d. 1 arom. H, J = 8.4 Hz), 6.82 (d, 1 arom. H. J = 8.4 Hz), 5.20 (s, C5-H), 4.89 (d, 1 H, C14OCH2, J = 12.1 Hz), 4.69 (d, 1H, C14OCH2, J = 12.1 Hz), 4.84 (d, 2H, C3OCH2, J = 2.2 Hz), 3.58 (t, 1 H, C=CH, J = 2.2 Hz), 2.94 (d, +NCH3, J = 4.4 Hz); MS (CI):mte465(M*+1). Example 19 Synthesis of 4,5a-epoxy-17-ethyl-3-methoxy-14p-[(3-phenylprOpyl)oxy]morphinan-6-one (compound 19). Compound 19 A mixture of 4,5a-epoxy-3-methoxy-14p-[(3-phenylpropyl)oxy]morphinan-6-one hydrochloride (see Example 1) (4.0 g, 8.77 mmol), K2C03 (8.0 g, 57.89 mmol), ethyl iodide (0.99 ml, 12.40 mmol) and 50 ml of water-free N,N-dimethylformamide was stirred for 5 h under N2 at 80°C (bath temperature). After filtration from the inorganic residue, the filtrate was evaporated down and the residue (4.7 g of brown oil) was purified using column chromatography (silica gel; CH2CI2/ MeOH / cone. NH4OH: 8 I: (250 / 2 / 0.5)); 0.5 I: (250 / 3 / 0.5), (250 / 4 / 0.5), (250 / 6 / 0.5), (250 / 8 / 0.5), (250 /10 / 0.5)). The evaporation residue (1.3 g of bright yellow oil) was crystallised out of MeOH. Yield: 1.2 g (30%) of compound 19. Fp. 95-10l°C; IR (KBr): 1719 (C=0) cm"1; 1H-NMR (DMSO-de): 6 7.30-7,13 (m, 5 arom. H), 6.73 (d, J = 8.2 Hz, 1 arom. H). 6.64 (d, J = 8.2 Hz, 1 arom. H), 4.76 (s, 1H, C5-H), 3.78 (s, 3H, OCH3), 0.96 (t, 3 H, N-CHj-CHa), J = 7 Hz); MS (CI): m/z 448 (M++1). Example 20 Synthesis of 4,5a-epoxy-17-ethyl-3-hydroxy-146-[(3-phenylpropyl)oxy]mofphrnan-6-one hydrochloride (compound 20.HCI). Compound 20 A solution of compound 19 (1.0 g, 2.23 mmol) in 48% HBr(10 ml) was reflux heated for 13 minutes. After cooling it was diluted with water (50 ml), ice was added, it was alkalised with cone, NH4OH and extracted with CH2CI2 (5 x 50 ml). The combined organic phases were washed with water (3 x 50 ml) and NaCI solution (1 x 50 ml), dried over Na2S04 and evaporated down. The evaporation residue (1.3 g of brown foamy resin) was purified using column chromatography (silica gel; CH2CI2 / MeOH / cone. NHjOH (250 : 2 : 0.5)). The evaporation residue (448 mg of yellow foamy resin) was dissolved in ether, etherial HCI added and the compound 20.HCI isolated. Yield: 380 mg (36%). Fp. 178-180°C; IR (KBr): 1724 (C=0) cm"1; 1H-NMR (DMSO-d6): 5 9.14 (s, OH), 7.29-7.03 (m, 5 arom. H), 6.56 (d. 1 arom. H, J = 8 Hz), 6.50 (d, 1 arom. H, J = 8 Hz), 4.69 (s, C5-H), 0.96 (t, 3H, N-CHrCH_3), J = 7.2 Hz); MS {CI): m/z434 (M++1). Example 21 Synthesis of 4,5a-epoxy-3-hydroxy-14p-[(3-methylbutyl)oxy]-17-propylmorphinan-6-one hydrochloride (compound 21.HCI). Compound 21 A solution of naloxone'HCI*2H20 (20.0 g, 50.0 mmol) and methane sulphonic acid (3.9 ml, 60.0 mmol) in 150 ml ethylene glycol was stirred for 18 h at a bath temperature of 80-90DC under N2. After the addition of 200 ml of ice-water and alkalising with cone. NH4OH extraction took place with CH2CI2 (2 x 100 ml, 2 x 50 ml). The combined organic phases were washed with H20 (2 x 100 ml) and saturated NaCI solution, dried over Na2S04 and evaporated down. The evaporation residue (beige crystals) was treated with boiling MeOH, whereby 16.52 g (89%) of colourless crystals of 4,5a-epoxy-3,14p-dihydroxy-17-(prop-2-enyl)morphinan-6-spiro-2'-(1,3-dioxolane) was obtained. Fp. 244-247°C; 1H-NMR (DMSO-d6): 6 8.87 (s, C3-OH), 6.54 (d, 1 arom. H, J = 8 Hz), 6.44 (d, 1 arom. H, J = 8 Hz), 5.93-5.70 (m, 1 olef. H), 5.27-5.04 (m, 2 olef. H), 4.79 (s, C14-OH), 4.33 (s, C5-H), 4.11-3.61 (m. 4H, C6(OCH2)2); MS (CI): m/z 372 (M++1). A mixture, consisting of 4,5a-epoxy-3,14p-dihydroxy-17-(prop-2-enyl)morphinan-6-spiro-2'-(1,3-dioxolane) (16.0 g, 43.1 mmol), K2C03 (16.2 g, 117 mmol), benzyl bromide (5.63 ml, 47.4 mmol) and 80 ml of water-free N,N-dimethylformamide was stirred for 24 h under N2 at room temperature. The inorganic material was filtered off, rinsed with CH2CI2 and the filtrate was evaporated down. The evaporation residue (white crystals) was treated for 1 h with reflux boiling ether to remove the solvent and the benzylbromide. The cooled mixture was filtered off, the remaining crystals washed again with a little cold ether and then treated with reflux boiling MeOH. 12.53 g (63%) of 3-benzyloxy-4,5a-epoxy-14[3-hydroxy-17-(prop-2-enyl)morphinan-6-spiro-2'-(1,3-dioxolane) was obtained as colourless crystals. Fp. 142-144°C; 1H-NMR (DMSO-d6): 5 7.50-7.22 (m, 5 arom. H), 6.77 (d, 1 arom. H, J = 8.0 Hz), 6.56 (d, 1 arom. H. J = 8.0 Hz), 5.95-5.68 (m, 1 H, 1 olef. H), 5,30-5.01 (m, 4 H, 2 olef. H, C3OCH2), 4.81 (s, OH'), 4.40 (s, C5-H), 4.08-3.65 (m, 4 H, C6(OCH2)2); MS (CI):m/z463(M++1). NaH (650 mg, 27 mmol) {obtained from 1.1 g of a 60% NaH dispersion in oil by washing with petroleum ether) was added to a solution of 3-benzyloxy-4,5a-epoxy-14B-hydroxy-17-(prop-2-enyl)morphinan-6-spiro-2'-(1,3-dioxolane) (5.00 g, 10.83 mmol) in 40 ml water-free N,N-dimethylformamide under N2 at 0DC (bath temperature) under stim'ng. After 15 min. 3,3-dimethylallylbromide (1.90 ml, 16.25 mmol) was added and the mixture first stirred for 1 h at 0°C (bath temperature) and then with reducing cooling stirred further for 4 hours. To terminate the reaction pieces of ice were added until no more hydrogen was produced. The mixture was poured onto 100 ml water and extracted with dichloromethane (3x 100 ml). The combined organic phases were washed with H20 (3 x 100 ml) and 250 ml of saturated sodium chloride solution, dried over sodium sulphate and evaporated down. The evaporation residue (6.02 g of yellow oil) was purified using column chromatography (silica gel; CH2CI2 / MeOH / cone. NH4OH (250 : 2 : 0.5)). The evaporation residue (5.01 g of bright yellow oil) was dissolved in ether and pure 3-benzyloxy-4,5a-epoxy-14p-[(3-methylbut-2-enyl)oxy-17-(prop-2-enyl)morphinan-6-spiro-2'-(1,3-dioxolane) hydrochloride was precipitated by the addition of etherial HCI. Yield: 4.83 g (79%); Fp. 122-124"C; 1H-NMR (DMSO-da): 6 8.61 (s, wide, *NH). 7.50-7.25 (m, 5 arom. H), 6.92 (d, J = 8.4 Hz, 1 arom. H), 6.70 (d, 3J = 8.4 Hz, 1 arom. H), 5.99-5.41 (m, 4 olefin. H), 5.14 (s, C3-OCH2), 4.57 (s. C5-H), 1.75 (s, 3 H, CH=CCH3), 1-66 (s, 3 H, CH=CCH3); MS (CI): m/z 531 (M*+1). A mixture of 3-benzyloxy-4,5a-epoxy-14p-[(3-methylbut-2-enyl)oxy>'l7-(prop-2-enyl)morphinan-6-spiro-2'-(1,3-dioxolane) hydrochloride (4.59 g, 8.11 mmol), 460 mg 10% Pd/C catalyst and 100 ml MeOH was hydrogenated for 4 h at room temperature and 30 psi. Then the catalyst was filtered off and the filtrate was evaporated down in a vacuum. The evaporation residue (slightly grey crystals) wasrecrystallisedoutof MeOH/ Et20. Yield: 3.54 g (91%) of pure4,5a-epoxy-3-hydroxy-14B-{(3-methylbutyl)oxy]-17-propylmorphinan-6-spiro-2'-(1,3-dioxolane) hydrochloride. Fp. 176-185°C; 1H-NMR (DMSO-da): 5 9.22 (s, OH), 8.12 (s, wide, 1 H, *NH), 6.68 (d, J = 8.0 Hz, 1 arom. H), 6.58 {d, J = 8.0 Hz, 1 arom. H), 4.46 (s, 1 H, C5-H), 4.11-3.62 (m, 4 H, C6(OCH2)2), 0.99-0.85 (m. 9 H, N*(CH2)2Cti3. CH(CH3)2); MS (CI): m/z 445 (M++1). A solution of 4,5a-epoxy-3-hydroxy-14p-[(3-methylbutyl)oxy]-17-propylmorphinan-6-spiro-2'-{1,3- dioxolane) hydrochloride (3.40 g, 7.1 mmol) in 40 ml MeOH /H20/conc. HCI (50 : 85:15) was reflux heated for 4 h. After the addition of H2O (50 ml) and alkalising with cone. NH4OH extraction was carried out with CH2CI2 (3 x 60 mi). The combined organic phases were washed with H20 (2 x 100 ml) and saturated NaCi solution, dried over Na2S04 and evaporated down. The evaporation residue (2.61 g of dark brown oil) was purified using column chromatography (silica gel; CH2CI2/ MeOH / cone. NH4OH (250 : 3 : 0.5}). From the evaporation residue (f.77 g of white foamy resin, 62%) a part (1.39 g) was dissolved in ether and 21.HCI (1.42 g) precipitated as a pure substance by the addition of etherial HCI. Fp. 175-185°C (decomp.); IR (KBr): 1725 (CO) cm'1; 1H-NMR (DMSO-d6): 5 9.52 (s, OH), 8.33 (s, wide, *NH), 6.70 (d, 1 arom. H, J = 8.2 Hz), 6.65 (d, 1 arom. H, J = 8.2 Hz), 4.91 (s, C5-H), 1.00-0.85 (m, 9 H, N*(CH2)2CH3, CH(CH3)2); MS (CI): m/z 401 (M*+1). Example 22 Synthesis of 58-benzyl-14-methoxycodeinone hydrochloride (= 5B-benzyl-7,8-didehydro-4.5a-epoxy- 3,14p-dimethoxy-17-methyl-morphinan-6-one hydrochloride) (compound 22.HCI). Compound 22 NaH (1.2 g, 50 mmol) (obtained from 2.0 g of a 60% NaH dispersion in oil by washing with petroleum ether) was added to a solution of 5B-benzyl-14-hydroxycodeinone (M. Gates et al., J. Org. Chem. 1989, 54, pp. 972-974) (7.95 g, 19.7 mmol) in 100 ml water-free N,N-dimethylformamide under N2 at 0"C (bath temperature) under stirring. After 15 min. dimethylsulphate (2.43 ml, 25.6 mmol) was added and the mixture stirred for 1 h at 0°C (bath temperature). To terminate the reaction pieces of ice were added until no more hydrogen was produced. The mixture was poured onto 250 ml water and extracted with dichloromethane (3 x 100 ml). The combined organic phases were washed with H20 (1 x 100 ml, 3 x 60 ml) and saturated sodium chloride solution, dried over sodium sulphate and evaporated down. From the evaporation residue (8.3 g of yellow-brown oil) a part was used further unmodified and the remainder (500 mg) purified using column chromatography (silica gel; CH2CI2/ MeOH / cone. NH4OH (250 : 2 : 0.5)). The evaporation residue (210 mg of yellow oil) was dissolved in ether and pure compound 22.HCI was precipitated by the addition of etherial HCI. Yield: 148 mg. Fp. 164-166°C; IR (KBr): 1680 (CO) cm1; 1H-NMR (DMSO-d6): 5 9.47 (s, wide, +NH), 7.37-7.09 (m, 5 arom. H), 7.04 (d, 1 H, C8H, J = 10.0 Hz), 6.84 (d, 1 arom. H, J =8.4 Hz), 6.74 (d, 1 arom. H,J=8.4 Hz), 6.29 (d, 1 H, CrH. J = 10.0 Hz), 3.76 (s, 3 H, C3OCH3), 3.59 (d, 1 H, C5-CH2, J = 15.1 Hz), 3.29 (d, 1 H, C5-CH2), J = 15.1 Hz), 2.98 (s, 3 H, C14-OCH3), 2.88 (d, 3H, *NCH3, J = 4.6 Hz); MS (CI): m/z419(M++1). Example 23 Synthesis of 5B-benzyM,5a-epoxy-3,14p-dimethoxy-17-methylmorphinan-6-one (compound 23). Compound 23 A mixture of unpurified compound 22 (6.96 g, 16.7 mmol of yellow-brown oil), 0.7 g 10% Pd/C catalyst and 150 ml MeOH was hydrogenated for 3 h at room temperature and 30 psi. Then the catalyst was filtered off and the filtrate was evaporated down in a vacuum. The evaporation residue (light brown foamy resin) was recn/stallised out of isoprapano), whereby 3.14 g (45%) of pure compound 23 was obtained. Fp. 136-138°C; IR (KBr): 1725 (CO) cm'1; 'H-NMR (CDCI3): 5 7.35-7.18 (m, 5 arom. H), 6.66 (d, 1 arom. H, J = 8.2 Hz), 6.57 (d, 1 arom. H, J = 8.2 Hz), 3.90 Example 24 Synthesis of 5p-benzyl-4,5a-epoxy-3-hydroxy-14p-methoxy-17-methylmorphinan-6-one hydrochloride (compound 24.HCI). Compound 24 A solution of compound 23 (2.90 g, 6.9 mmol) in 40 ml of 48% hydrobromic acid was reflux heated for 15 min. Then the solution was cooled and evaporated down. The evaporation residue was dissolved in MeOH and again evaporated down. The resulting foamy resin (2.50 g) was converted to the base and purified using column chromatography (silica gel; CH2C!2/ MeOH / cone. NH4OH (250 : 3 : 0.5)). The evaporation residue (2.27 g of yellow oil) was dissolved in ether and the pure compound 24.HCI precipitated with etherial HCI. Yield: 2.30 g (75%); Fp. 222-224°C; IR (KBr): 1725 (CO) cm-1; 'H-NMR (DMSO-d6): 6 9.45 (s, OH), 9.38 (s, wide, *NH), 7.37-7.09 (m, 5 arom. H), 6.70 (d, 1 arom. H, J = 8.2 Hz), 6.62 (d, 1 arom. H, J = 8.2 Hz), 3.41 (s, OCH3), 2.89 (d, 3 H, +NCH3, J = 3.4 HZ); MS (CI): m/z407 (M*+1). Example 25 Synthesis of 4-hydroxy-3-methoxy-17-methyl-14-E(3-phenylpropyl)oxy]-morphinan-6-one (compound 25). Compound 25 A mixture of 4,5a-epoxy-3-methoxy-17-methyl-14-[(3-phenylpropyl)oxy]-morphinan-6-one (= 14-0-(3-phenylpropyl)oxycodon) (see Example 1)(600mg, 1.4 mmol), ammonium chloride (0.97 g, 18.0 mmol) and 30 ml MeOH was reflux heated under stirring. Then within 5 minutes activated zinc powder (0.94 g, 14.0 mmol) was added in portions and the mixture reflux heated for 6 h. After filtration from the inorganic residue, the filtrate was evaporated down, alkalised with cone. NH4OH, extracted with CHjCb {3 x 40 ml), washed with H20, dried over Na2S04 and evaporated down. The evaporation residue (605 mg) was crystallised out of a little MeOH. Yield: 562 mg (86%) of compound 25. Fp. > 258°C (decomp.); IR (KBr): 3145 (OH), 1734 (CO) cm-1; 1H-NMR (CDCI3): 6 7.37-7.05 (m, 5 arom. H), 6.64 (d, 1 arom. H, J = 8.3 Hz), 6.54 (d, 1 arom. H, J = 8.3 Hz), 3.79 (s, OCH3), 2.30 (s, NCH3); MS (CI): m/z 436 (M*+1), Example 26 Synthesis of 3,4-dimethoxy-17-methyl-14-[{3-phenylpropyl)oxy]morphinan-6-one salicylate (compound 26, C7H603). Compound 26 A mixture of compound 25 (200 mg, 0.5 mmol), K2C03 (420 mg, 3.0 mrnol) and phenyltrimethyl ammonium chloride (254 mg, 1.5 mmol) and 50 ml water-free N,N-dimethylformamide was stirred for 9 h at 80°C (bath temperature) under N2. After filtration from the inorganic residue, the filtrate was evaporated down, and the evaporation residue was purified using column chromatography (silica gel; ChbCfe/MeOH/conc. NH4OH (93 : 7 : 1)). The evaporation residue (250 mg of foamy resin) was dissolved in MeOH and salicylic acid added to it. 102 mg (41%) of the compound 26.C7H603 was isolated. Fp. 110-115°C; IR (KBr): 1720 (CO) cm'1; 1H-NMR (CDCI3): 6 7.29-7.18 (m, 5 arom. H), 6.75 (s, 2 arom. H), 3.93 (s, C4-OCH3), 3.80 (s, C3-OCH3), 2.31 (s, NCH3); MS (CI): m/z450 (M*+1). Example 27 Synthesis of 14p-benzyloxy^-hydroxy-3-methoxy-17-methylmorphinan-6-one hydrochloride (compound 27.HCI). Compound 27 Amixtureof4,5a-epoxy-14p-hydroxy-3-methoxy-17-methylmorphinan-6-spiro-2'-(1.3-dioxolane) (Lester etal. 1965, 21, p. 771) (6.0 g, 16.69 mmol), NaH (2.16 g, 90.0 mmol), obtained from 3.6 g of 60% dispersion by washing with petroleum ether) and 150 ml water-free N,N-dimethylformamide was stirred for 20 min. at 0°C {bath temperature) under N2. After the addition of benzylbromide (4.0 ml, 33.39 mmol) it was stirred further for 16 h at room temperature. Then pieces of ice were added until no more H2 was given off, it was diluted with water (100 ml) and extracted with CH2CI2 (1 x 250 ml, 3 x 150 ml, 1 x 100 ml). The combined organic phases were washed with water (4 x 250 ml) and NaCI solution (1 x 250 ml), dried over Na:S04 and evaporated down. The evaporation residue (7.47 g of red-brown oil) was crystallised out of MeOH (12 ml). 6.01 g of colourless 4,5a-epoxy-140-benzyloxy-3-methoxy-17-methylmorphinan-6-spiro-2'-(1,3-dioxolane)was isolated. The mother liquor was evaporated down and purified using column chromatography (silica gel; CH2CI2/ MeOH / cone. NH4OH: 2 I: (250 / 2 / 0.5); each 1 I: (250 / 4 / 0.5), (250 / 6 / 0.5), (250 / 8 / 0.5), (250 /10 / 0.5)). The evaporation residue (551 mg, bright yellow oil) was crystallised out of MeOH (1 ml). Total yield: 6.32 g (84%) of4,5a-epoxy-14p-benzyloxy-3-methoxy-17-methylmorphinan-6-spiro-2'-(1,3-dioxolane). Fp. 121-124°C; 1H-NMR (DMSO-d6): 5 7.44-7.26 (m, 5 arom. H), 6.74 (d, 1 arom. H, J = 8.2 Hz), 6.60 (d, 1 arom. H, J = 8.2 Hz), 4.55 (d, 1 aliph. H, 14-Q-CH2.CRH*. J = 11.2 Hz), 4.41 (s, C5-H), 4.31 (d, 1 aliph. H, 14-0-0^-0^5, J = 11.2 Hz), 4.02-3.67 (m, 4 H, OCH2CH20), 3.77 (s, OCH3); 2.31 (s, NCH3); MS (CI): m/z 450 (M++1). A solution of 4,5a-epoxy-143-benzyloi:y-3-methoxy-17-methylmorphinan-6-spiro-2'-(1r3-dioxolane) (957 mg, 2.13 mmol) in MeOH (15 ml) and 2N HCI (22.5 ml) was reflux heated for 4 h. After cooling, it was diluted with water (20 ml), alkalised with cone. NH4OH and extracted with CH2CI2 (1 x 100 ml, 1 x 50 ml, 3 x 25 ml). The combined organic phases were washed with water (1 x 100 ml) and NaCI solution (1 x 100 ml), dried over Na2S04 and evaporated down. The evaporation residue (879 mg of dark yellow oil) was crystallised out of MeOH. Yield: 801 mg (89%) of 14B-benzyloxy-4,5a-expoxy-3-methoxy-17-methylmorphinan-6-one. Fp. 136-138°C; IR (KBr): 1721 (CO) cm'1; 1H-NMR (CDCI3): 6 7.45-7.24 (m, 5 arom. H), 6.68 (d. 1 arom. H, J = 8.3 Hz), 6.62 (d, 1 arom. H, J = 8.3 Hz), 4.77 (d, 1 H, OCH2Ph, J = 10.3 Hz), 4.64 (s, CH-5). 4.37 (d, 1 H, OCH2Ph, J = 10.3 Hz), 3.88 (s, CH30), 2.39 (s, CH3N); MS (CI): m/z 406 (M++1). Zinc powderwas carefully added in portions (totalling 1.4 g, 21.45 mmol) to a reflux boiling mixture of 14B-benzyloxy-4,5a-expoxy-3-methoxy-17-methylmorphinan-6-one (870 mg, 2.15 mmol), NH4CI (1.4 g, 26.21 mmol) and MeOH (40 ml) under stirring. The mixture was reflux heated for 2 h. After filtration from the inorganic material, the filtrate was evaporated down, water (40 ml) was added to the evaporation residue, extracted with a mixture of CH2CI2 and isopropanol (3:1) (3 x each with 40 ml), the combined organic phases washed with water (1 x 20 ml) and NaCI solution (1 x 20 ml), dried over Na2S04 and evaporated down. The evaporation residue (961 mg of white foamy resin) was purified using column chromatography (silica gel; CH2CI2/ MeOH / cone. NH4OH (250 : 4 : 0.5)). The evaporation residue (750 mg) was dissolved in ether and etherial HCI added to it. Yield: 730 mg (77%) of compound 27.HCI. Fp. >220-224°C (decomp.); IR (KBr): 1714 (C=0) cm"1; 'H-NMR (DMSO-d6): 6 9.26 (s, wide, *NH), 8.84 (s, C4-OH), 7.55-7.31 (m, 5 arom. H), 6.91 (d, 1 arom. H, J = 8.2 Hz), 6.68 (d, 1 arom. H, J = 8.2 Hz), 4.87 (d, 1 aliph. H. OCHgCfiH*, J = 11.6 Hz). 4.66 (d, 1 aliph. H, OCHjC6Hs, J = 11.6 Hz), 3.76 (s, C3-OCH3), 2.88 Example 28 Synthesis of 14B-benzyloxy-3,4-dimethoxy-17-methylmorphinan-6-one hydrochloride (compound 28.HCI). Compound 28 A mixture of 27.HCI (343 mg, 0.84 mmol), K2C03 (353 mg, 2.52 mmol) and phenyltrimethyl ammonium chloride (285 mg, 1.68 mmol) and N,N-dimethylformamide (25 ml) was stirred for 4 h at 80°C {bath temperature) under N2. After filtration from the inorganic material, the filtrate was evaporated down, the evaporation residue (red-brown oil) dissolved in CH2Cl2 (50 ml), washed with water (2 x 20 ml) and NaCI solution (1 x 20 ml), dried over Na2S04 and evaporated down. The evaporation residue (470 mg of brown oil) was purified using column chromatography (silica gel; CH2CI2 / MeOH / cone. NH„OH: each 1 I: (250 / 2 / 0.5), (250 / 3 / 0.5), (250 / 4 / 0.5), (250 / 6 / 0.5), (250 / 8 / 0.5)). The evaporation residue (280 mg, yellow oil) was dissolved in ether and precipitated as compound 28.HCI using etherial HCI. Yield: 251 mg (66%); Fp. 140-145°C; IR (KBr): 1710 (C=0) cm"1; ^-NMR (DMSO-d6): 5 9.27 (s, wide, *NH), 7.53-7.30 (m, 5 arom. H), 7.02 (d, 1 arom. H, J = 8.4 Hz), 6.91 (d, 1 arom. H, J = 8.4 Hz), 4.84 (d, 1 aliph. H, OCH2CEHS) J = 11 Hz), 4.64 (d, 1 aliph. H, OCH2C6H5), J - 11 Hz), 3.78 and 3.82 (2 s, 2 OCH3), 2.87 (s, +N-CH3); MS (CI): m/z 422 (M*+1). Example 29 Synthesis of 4-hydroxy-3-methoxy-17-methyl-14p-[(2-naphthylmethyl)oxy]morphinan-6-one hydrochloride (compound 29.HCI). Compound 29 A mixture of 4,5a-expoxy-14B-hydroxy-3-methoxy-17-methylmorphinan-6-spiro-2'-(1.3-dio>!olane) (Lester etal., 1965, 21, p. 771) (1.96 g, 5.45 mmol), NaH (682 mg, 28.43 mmol, obtained from 1.14 g of 60% dispersion by washing with petroleum ether) and 40 ml of water-free N,N-dimethylformamide was stirred for 45 min. at 0°C (bath temperature) under N2. After the addition of 2-bromomethylnaphthalin (96%, 2,31 g, 10.9 mmol) stirring continued for 2 h at 0°C (bath temperature). Then small ice pieces were added until no more H2 was given off, the mixture was diluted with water (50 ml) and extracted with CH2CI2 (3 x 50 ml, 2 x 25 ml). The combined organic phases were washed with water (4 x 50 ml) and NaCI solution (1 x 250 ml), dried over Na2S04 and evaporated down. The crystalline evaporation residue (1.26 g) was treated twice each time with 10 ml of reflux boiling MeOH for purification. Yield: 960 mg (35%) of 4,5-expoxy-3-methoxy-17-methyl-14p-[(2-naphthylmethyl)oxy]morphinan-6-spiro-2'-(1.3-dioxolane). Fp. 184-185X; 1H-NMR (DMSO-de): 6 7.93-7.89 (m, 4 arom. H), 7.62-7.48 (m, 3 arom. H), 6.75 (d, 1 arom. H, J = 8.2 Hz), 6.62 (d, 1 arom. H, J = 8.2 Hz), 4.72 (d, 1 atiph. H, OCH^naphthyl, J = 11.4 Hz), 4.47 (d, 1 aliph. H, OCHgnaphthyl, J = 11.4 Hz), 4.43 (s, C5-H), 4.06-3.68 (m, 4 H, OCH2CH20), 3.78 (s, OCH3), 2.34 (s, N-CH3); MS (CI): m/z 500 (M++1). A solution of 4,5a-expoxy-3-methoxy-17-methyl-14p-[(2-naphthylmethyl)oxy]-morphinan-6-spiro-2'-(1,3-dioxolane) (2,3 g, 4.60 mmol) in MeOH (30 ml) and 2N HCI (45 ml) was reflux heated for4 h. After cooling, it was diluted with water (40 ml), alkalised with cone. NH4OH and extracted with CH2CI2 (1 x 200 ml, 1 x 100, 3 x 50 ml). The combined organic phases were washed with water (1 x 200 ml) and NaCI solution (1 x 200 ml), dried over Na2S04 and evaporated down. The evaporation residue (1.84 g of dark yellow oil) was crystallised out of MeOH. Yield: 1.63 g (78%) 4,5a-expoxy-3-methoxy-17-methyl-14B-[(2-naphthylmethyl)oxy]-morphinan-6-one. Fp. 195-199°C; IR (KBr): 1724 (vC=0) cm-1; 1H-NMR (DMSO-d6): 5 8.00-7.90 (m, 4 arom. H), 7.68-7.48 (m. 3 arom. H), 6.77 (d, 1 arom. H, J = 8.2 Hz), 6.70 (d. 1 arom. H, J = 8.2 Hz), 4.88 (s, C5-H), 4.84 (d, aliph. H, 14QCHr naphthyl, J = 11.2 Hz), 4.64 (d, 1 aliph. H, 14QCHr naphthyl, J = 11.2 Hz), 3.80 (s, 30CH3), 2.37 (s, N-CH3); MS (CI): m/z 456 (M*+1). Zinc powder was added in portions (totalling 1.75 g, 26.76 mmol) to a reflux boiling mixture of 4,5a-expoxy-3-methoxy-17-methyl-14(3-[(2-naphthylmethyl)oxy]-morphinan-6-one (1.0 g, 2.20 mmol), NH4CI (1.75 g, 32.71 mmol) and MeOH (42 ml) under stirring. The mixture was reflux heated for 3 h. After filtration from the inorganic residue and washing with MeOH, the filtrate was evaporated down, water (40 ml) added to the evaporation residue, alkalised with cone. NH40H and extracted with CH2CI2 (1 x 70 ml, 2 x 50 ml). The combined organic phases were washed with water (1 x 40 ml), 1 x 30 ml) and NaCI solution (1 x 30 ml), dried over Na2S04 and evaporated down. The evaporation residue (1.09 g of light brown foamy resin) was purified using column chromatography (silica gel; CH2CI2/ MeOH / cone. NH*OH: 1.5 I: (250 / 2 / 0.5); 0.5 I each of: (250 / 3 / 0.5), (250 / 4 / 0.5), (250 / 6 / 0.5). The evaporation residue (836 mg of beige foamy resin) was dissolved in ether and compound 29 was precipitated out as the hydrochloride (29.HCI) with etherial HCI. Yield: 729 mg (68%); Fp. 195-197°C; IR (KBr): 1710 (C=0) cm-1; 1H-NMR (DMSO-d6): 6 9.24 (s, wide, +NH), 8.86 (s, 4-OH), 8.02-7.91 (m, 4 arom. H, naphthyl), 7.70-7.48 (m, 3 arom. H, naphthyl), 6.91 (d. 1 arom. H, J = 8.2 Hz), 6.69 {d, 1 arom. H, J = 8.2 Hz), 5.01 (d, 1 aliph. H, 140CHrnaphthvl, J = 12 Hz), 4.82 (d, 1 aliph. H, 140CHrnaphthvl. J = 12 Hz), 3.77 (s, 30CH3), 2.90 (ps-d, *NCH3); MS (CI): m/z 458(M*+1). Example 30 Synthesis of 3,4nJimethoxy-17-methyl-14B-[(2-naphthylmethyl)oxy]morphinan-6-one hydrochloride (compound 30.HCI). Compound 30 A mixture of 29.HCl (316 mg, 0.64 mmol), K2C03 (304 mg, 2.17 mmol), phenyltrimethyl ammonium chloride (280 mg, 1.53 mmol) and N,N-dimethylformamide (25 ml) was stirred at 80°C (bath temperature) under N2 for 2 h. After filtration from the inorganic material, the filtrate was evaporated down, the evaporation residue (red-brown oil) absorbed in CHaCI2 {50 ml), washed with water (2 x 20 ml) and NaCI solution (1 x 20 ml), dried over Na2S04 and evaporated down. The evaporation residue (237 mg of brown oil) was purified using column chromatography (silica gel; CH2CI2 / MeOH / cone. NH4OH: 1.5 I: (250 / 2 / 0.5); 0.5 I each of: (250 / 3 / 0.5), (250 / 4 / 0.5), (250 / 6 / 0.5), (250 / 8 / 0.5). The evaporation residue (265 mg of beige foamy resin) was dissolved in ether and compound 30 was precipitated out as the hydrochloride (30.HCl) with etherial HCl. Yield: 257 mg (80%): Fp. 165-170°C; IR (KBr): 1712 (C=0) on1; 1H-NMR (DMSO-da): 6 9.27 (s, wide, *NH), 8.03-7.91 (m, 4 arom. H), 7.70-7.51 (m, 3 arom. H), 7.05 (d, 1 arom. H, J =8.6 Hz), 6.97 (d, 1 arom. H, J = 8.6 Hz), 5.01 (d, 1 aliph. H, 14QCHrnaohthyl. J = 11.6 Hz), 4.83 (d, 1 aliph. H, 14QCH2-naphthyl. J = 11.6 Hz), 3.84 and 3,79 (s, 2 OCH3), 2.90 (d, *NCH3); MS (CI): m/z 472 (lvT+1). Example 31 Synthesis of 4-hydroxy-3-methoxy-5p,17-dimethyl-143-[(3-pheny[propyl)oxy]fnorphinan-6-one hydrochloride {compound 31.HCI). Compound 31 Zinc powder was added in portions (totalling 5.5 g, 84.12 mmol) to a reflux boiling mixture of 4,5a-expoxy-3-methoxy-5p,17KJimethyl-14p-[(3-phenylpropyl)oxy]morphinan-6-one (see Example 17) (3.7 g, 8.27 mmol), NH4CI (4.5 g, 83.87 mmol) and EtOH (50 ml) under stirring. The mixture was reflux heated for 47 h. After filtration from the inorganic residue and washing with EtOH, the filtrate was evaporated down, water (200 ml) added to the evaporation residue (6.35 g of white foamy resin), alkalised with cone. NH4OH and extracted with CH2CIZ (1 x 100 ml, 4 x 50 ml). The combined organic phases were washed with water (4 x 200 ml) and NaCI solution (1 x 200 ml), dried over Na2S04 and evaporated down. The evaporation residue (3.93 g of yellow oil) was purified using column chromatography (silica gel; CH2CI3/ MeOH / cone. NH4OH (250 / 2 / 0.5). 2.99 g (80%) of the pure compound 31 was obtained as a yellow oil. 500 mg of it was dissolved in ether and the compound 31 was precipitated out as the hydrochloride (31.HCI) with etherial HCI. Fp. >210°C (decomp.); IR (KBr): 1700 (C=0) cm*1; 'H-NMR (DMSO-d6): 5 9.64 (s, C4-OH), 8.88 (s, wide, *NH), 7.33-7.17 (m, 5 arom. H), 6.91 (d, 1 arom. H, J = 8.2 Hz), 6.70 (d, 1 arom. H, J = 8.2 Hz), 3.78 (s, 30CH3), 2.80 (d, +NCH3, J = 3.4 Hz), 1.28 (d, C5-CH3, J = 6.6 Hz); MS (CI): m/z 450 (Ivf+1). Example 32 Synthesis of 3,4-dimethoxy-5B,17-dimethyl-14B-[(3-phenylpropyt)oxy]morahinan-6-one hydrochloride (compound 32.HCI). Compound 32 Compound 31 (base) {1.55 g, 3.44 mmol) was dissolved in 20 g of 40% tetrabutyl ammonium hydroxide solution at room temperature under N2. Then a solution of dimethyl sulphate (0.48 g, 3.8 mmol) in 15 ml of dichloromethane was added. The mixture was vigorously stirred for 12.5 h at room temperature under H2 and then 300 ml water and 50 ml dichloromethane were added. The aqueous phase was extracted with dichloromethane (2 x 50 ml). The combined organic phases were washed with cone, ammonia (1 x 50 ml), water (6 x 200 ml) and saturated sodium chloride solution (1 x 200 ml), dried over sodium sulphate and evaporated down. The evaporation residue (1.25 g of yellow oil) was purified using column chromatography (silica gel; CH2Cl2 / MeOH / cone. NH4OH (250 / 2 / 0.5).1.0 g (53%) of the pure compound 32 was obtained as a yellow oil. 810 mg of it was dissolved in ether and the compound 32 was precipitated out as the hydrochloride (32.HCI) with etherial HCI. Fp. 135-138°C; IR (KBr): 1700 (C=0) cm"1; 1H-NMR (DMSO-d6): 6 9.36 (s, wide, +NH), 7.31-7.21 (m, 5 arom. H), 7.05 (d, 1 arom. H, J = 8.4 Hz), 6.95 (d, 1 arom. H, J = 8.4 Hz), 3.80 and 3.79 (2 s, 2 OCH3), 2.81 (d, *NCH3, J = 4.8 Hz), 1.25 (d, C5-CH3, J = 7 Hz); MS (CI): m/z 464 (M*+1). Example 33 Synthesis of 14B-ethoxy-4-hydroxy-3-methoxy-5B,17-dimethylmorphinan-6-one (compound 33). Compound 33 Zinc powder was added in portions {totalling 15.0 g, 229,4 mmol) to a reflux boiling mixture of 4,5a-expoxy-14(S-ethoxy-3-methoxy-5(M7-dimethylmorphinan-6-one (Schmidharnrner et al., Helv. Chim. Acta 1990, 73, pp. 1784-1787) (3.0 g, 8.4 mmoi), NH„CI (15.0 g, 280.1 mmol) and MeOH (30 mi) under stirring. The mixture was reflux heated for 24 h. After filtration from the inorganic residue and washing with MeOH, the filtrate was evaporated down, the evaporation residue alkalised with diluted NH4OH and extracted with a mixture of CH^CIj and MeOH (2:1) (1 x 100 ml, 3 x 30 ml). The combined organic phases were dried over Na2S04 and evaporated down. The evaporation residue (2.82 g of brown foamy resin) was crystallised out of MeOH and in this way 684 mg of pure compound 33 was obtained. The mother liquor was evaporated down and the evaporation residue (1.895 g of brown foamy resin) was used for the production of the compound 34 without further purification. Compound 33: Fp. 122-129°C; IR (KBr): 3480 (OH), 1715 (C=0)cm'1; 1H-NMR (CDCI3): 5 6.67 (d, 1 arom. H, J = 8.0 Hz), 6.57 (d, 1 arom. H, J = 8.0 Hz), 3.82 (s, OCH3), 2.32 (s, NCH3), 1.54 (s, C5-CH3), 1.18 (t, CH3CH2, J = 5.7 Hz); MS (CI): m/z 360 (M++1). Example 34 Synthesis of 143-ethoxy-3,4-dimethoxy-5B,l7-dimethylmorphinan-6-one salicylate (compound 34.C7H603). Compound 34 A mixture of the compound 33 (1,895 g, 5.3 mmol) (evaporation residue of the mother liquor, see above), KzC03 (2.12 g, 15.3 mmol), phenyltrimethyl ammonium chloride (1.8 g. 10.5 mmol) and water free N.N-dimethylformamide (20 ml) was stirred at 80°C (bath temperature) under N2 for 3 h. After filtration from the inorganic material and washing with dichloromethane, the filtrate was evaporated down. The evaporation residue was dissolved in dichloromethane, washed with water (2 x 50 ml) and saturated NaCI solution (1 x 50 ml), dried over sodium sulphate and evaporated down. The evaporation residue (2.11 g of dark brown oil) was purified using column chromatography (basic aluminium oxide, activity level 111; dichloromethane). The evaporation residue was crystallised as compound 34.C7H603 with salicylic acid in diisopropylether. Yield: 1.32 g (49%). Fp. 135*141 DC; IR (KBr): 3400 (*NH, OH), 1710 (C=0), 1630 (C02) cm"1; 1H-NMR (CDCI3): 6 7.88 (m, *NH), 7.27 (m, 2 arom. H), 6.81 (m, 4 arom. H), 3.86 (s, OCH3), 3.83 (s, OCH3). 2.84 (s, *NCH3), 1.40 (d. C5-CH3, 5.8 Hz), 1.17 (t, CH3CH2, J = 5.3 Hz); MS (CI): m/z 374 (Nf+1). Example 35 Synthesis of 14p-benzyloxy-3,4-dimethoxy-5B,17-dimethylmorphinan-6-one (compound 37). Compound 37 Zinc powder was added in portions (totalling 10.5 g, 160.6 mmol)to a reflux boiling mixture of 4,5a-expoxy-3-methoxy-5(3,17-dimethyl-14p-hydroxymorphinan-6-one (Schmidhammeretal., Helv. Chim. Acta 1988, 71, pp. 1801-1804) (4.17 g, 12.66 mmol), NH4CI(7.0g, 130.87 mmol) and EtOH (50 ml) under stirring. The mixture was reflux heated for 68 h. After filtration from the inorganic residue and washing with EtOH, the filtrate was evaporated down, water (150 ml) was added to the evaporation residue (7.65 g of white foamy resin), it was alkalised with cone. NH40H and extracted with CH2C\21 isopropanol (3:1) (2 x 80 ml, 1 x 60 ml, 1 x 40 ml). The combined organic phases were washed with water (3 x 70 ml) and NaCI solution (1 x 70 ml), dried over Na2S04 and evaporated down. The evaporation residue (5.02 g of brown oil) was crystallised out of CH2CI2 / isopropanol (5:3) to form compound 35 (4,14P-dihydroxy-3-methoxy-5(S,17-dimethylmorphinan-6-one) (3.39 g, (81%). 200 mg of it was dissolved in acetone and 135 mg was precipitated with etherial HCI to give the compound 35.HCI: Fp. >185°C (decomp.); IR (KBr): 3200 (OH), 1700 (C=0) cm"1; Analytical data of the base compound 35:1H-NMR (DMSO-ds); 6 8.43 (s, C-OH), 6.77 (d, 1 arom. H, J = 8.2 Hz), 6.57 (d, 1 arom. H, J = 8.2 Hz), 4,49 (s, Cu-OH). 3.74 (s, C3-OCH3), 2.25 (s, NCH3), 1.30 (d, C5-CH3, J = 7.4 Hz);MS(CI):m/z332(M++1). Compound 35 Compound 35 (base) (9.5 g, 28.67 mmol) was dissolved in 45 g of 40% tetrabutyl ammonium hydroxide solution at room temperature under N2. Then a solution of dimethyl sulphate (2.75 ml (=3.67 g), 29.06 mmol) in 50 ml of dichloramethane was added. The mixture was vigorously stirred at room temperature for 5 h under N2and then 100 ml of water was added. The aqueous phase was extracted with dichloromethane (3 x 50 ml). The combined organic phases were washed with 2 M ammonia solution (1 x70 ml), water (12 x 100 ml) and saturated sodium chloride solution (1 x 100) ml, dried over sodium sulphate and evaporated down. The evaporation residue (8.16 g of light coloured oil) was crystallised out of 4 mJ MeOH. Yield: 5.06 g (51%) 143-hydroxy-3,4-dJmett}oxy-5B-17-dimethylmorphinan-6-one (compound 36). Fp. 122-124"C; IR (KBr): 1704 (C=0) cm"1; 1H-NMR (CDCI3): 6" 6.78 (s, 2 arom. H), 4.31 (s, C14-OH), 3.87 and 3.82 (2 s, 2 OCH3), 2.32 (s, NCH3); 1.28 (d, C5-CH3, J = 6.8 Hz); MS (CI): m/z 346 (M++1). A mixture of compound 36 (7.42 g, 21.48 mmol), 2.20 ml methane sulphonic acid (3.26 g, 33.93 rnmol) and 100 ml diethylene glycol was stirred for 1 h under N2 and at a bath temperature of 80°C. Then the mixture was poured onto 600 ml of ice-water, alkalised with concentrated ammonia and extracted with dichloromethane (1 x 200 ml, 4 x 50 ml). The combined organic phases were washed with water (5 x 200 ml) and saturated sodium chloride solution (1 x 200 ml), dried over sodium sulphate and evaporated down. The evaporation residue (8.13 g of reddish crystals) was recrystallised out of 8 ml methanol. Yield; 4.91 g (59%) of 14B-hydroxy-3,4-dimethoxy-5B,17-dimethylmorphinan-6-spiro-2'-(1,3-dioxolane), Fp. 155-157°C; 1H-NMR (CDCl3y. o 6.76 (s, 2arom. H), 4.36 (s, C14-OH), 3.91-3.57 (m, 4 H, OCH2CH20-C), 3.83 and 3.74 (2 s, 2 CH30), 2.30 (s, CH3N), 1.35 (d. C5-CH3, J = 5.2 Hz); MS (CI): m/z 390 (M*+1). NaH (0.13 g, 5.41 mmol) (obtained from 0.21 g of a 60% NaH dispersion in oil by washing with petroleum ether) was added to a solution of 14B-hydroxy-3,4-dimethoxy-5B,17-dimethylmorphinan-6-spiro-2'-(1.3-dioxolane)(1.00 g, 2.57 mmol) in 100 ml water-free N,N-dimethylformamide under N2 at 0°C (bath temperature) under stirring. After 15 min. benzyl bromide (0.88 g, 5.14 mmol) was added and the mixture stirred for 3 h at room temperature. Then the excess sodium hydride was broken down with pieces of ice, the reaction mixture was poured onto 300 ml water and extracted with dichloromethane / isopropanol (5 :2) (3 x 70 ml). The combined organic phases were washed with H20 (5 x 200 ml) and a saturated sodium chloride solution (1 x 200 ml), dried over sodium sulphate and evaporated down. The evaporation residue (1.65 g of yellowish crystals) was crystallised out of 2 ml ethanol. Yield: 0.65 g (53%) 14B-benzyloxy-3,4-dimethoxy-5B,17-dimethyImon?hinan-6-spiro-2'-(1,3-dioxolane). Fp. 201-202°C; 1H-NMR (CDCI3): 5 7.49-7.23 (m, 5 arom. H), 6.77 (s, 2 arom. H), 4.61 (d, 1 H, PhCHp, J = 10.5 Hz), 4.29 (d, 1 H, PhCH^O, J = 10.5 Hz), 3.88-3.56 (m, 4 H, OCH2CH20), 3.83 and 3.76 (2 s, 2 CH30), 2.30 (s, CH3N), 1.25 (d, C5-CH3, J = 7.4 Hz); MS (CI): m/z480(M++1). A solution of 14B-benzyioxy-3,4-dimethoxy-5p,17-dimethylmorphinan-6-spiro-2*-{1.3-dioxolane)(0.50 g, 1.04 mmol) in 10 ml of a mixture of 5 ml methanol, 4 ml water and 1 ml cone. HCI was reflux heated for 30 minutes. Then the mixture was poured onto 150 ml of ice-water, alkalised with concentrated ammonia and extracted with dichloromethane / isopropanol (4 :1) (2 x 50 ml, 2 x 25 ml). The combined organic phases were washed with water (2 x 100 ml) and a saturated sodium chloride solution (1 x 100 ml), dried over sodium sulphate and evaporated down. The evaporation residue (0.51 g of light coloured oil) was crystallised out of 1 ml methanol. Yield: 0.34 g (76%) of compound 37. Fp. 166-167°C; IR (KBr): 1695 (CO) cm'1; 1H-NMR (CDCI3): 6 7.34-7.21 (m, 5 arom. H), 6.83 (d, 1 arom. H, J = 8.6 Hz). 6.78 (d, 1 arom. H, J = 8.6 Hz), 4.63 (d, 1H, PhCHp, J = 10.8 Hz), 4.32 (d, 1 H, PhCHjO, J = 10.8 Hz}, 3.86 and 3 83 (2s, 2CH30), 2.30 (s, CH3N), 1.43 (d, C5-CH3, J = 7.0 Hz); MS (CI): m/z 436 (M*+1). Example 36 Synthesis of 4,5a-epoxy-3-hydroxy-17,17-dimethyl-6-oxo-14p-[(3-phenylpropyl)oxy]moiphinanium- iodide (compound 38). Compound 38 A solution of 4,5a-epoxy-3-methoxy-17-methyl-14-E(3-phenylpropyl)oxy]morphinan-6-one (= l4-0-(3-phenylpropyl)oxycodon; see Example 1) {3.0 g, 6.90 mmol) in 48% HBr (30 ml) was reflux heated for 15 minutes. After the reaction had finished, the solution was cooled with ice, alkalised with cone. NH4OH and extracted with CH2CI2 (5 x 50 ml). The combined organic phases were washed with water (3 x 50 ml) and a saturated NaCI solution (1 x 50 ml), dried over Na2S04 and evaporated down. The evaporation residue (3.5 g of brown oil) was purified using column chromatography (silica gel; CH2CI2/ MeOH / cone. NH„OH: 6 I: (250 / 2 / 0.5): each 0.5 I: (250 / 3 / 0.5), (250 / 4 / 0.5), (250 / 6 / 0.5), (250 / 8 / 0.5)). The evaporation residue (4,5a-epoxy-3-hydroxy-17-methyl-148-[(3-phenylpropyl)oxy]morphinan-6-one, 1.36 g of yellow oil, 47%) could not be crystallised. Therefore one part was passed as oil to the next reaction and the remainder converted as usual to the hydrochloride (4,5a-epoxy-3-hydroxy-17-methyl-i4|3-[(3-phenylpropyl)oxy]morphinan-6-one hydrochloride). Analytical data of the hydrochloride: Fp. 185-189°C; 'H-NMR (DMSO-d6): 6 9.50 (s, C3-OH), 8.68 (s, wide, *NH), 7.34-7.16 (m, 5 arom. H), 6.70 (d, 1 arom. H, J = 8.0 Hz), 6.65 (d, 1 arom. H, J = 8.0 Hz), 4.87 (s, C5-H), 2.92 (d, *NCH3). . solution of 4,5a-epoxy-3-hydroxy-17-methyl-l4(3-[(3-phenylpropyl)oxy]morphinan-6one (oil, 257 ig, 0.61 mmol) and methyl iodide (0.38 ml, 6.11 mmol) in acetonitrile (10 ml) was stirred for 2 days 150°C (bath temperature) under N2. A DC examination showed that the reaction was not oncluded. Therefore further methyl iodide (0.38 ml, 6.11 mmol) was added and the solution stirred jrtherfor3 days under the same conditions. Then the solvent was evaporated off and the vaporation residue (367 mg of yellow foamy resin) was purified using column chromatography silica gel; CH2CI2/MeOH (10:1)). Evaporation residue 240 mg (71%) amorphous compound 38. Fp. 64-1708C; IR (KBr): 1723 (C=0) cm"1; 1H-NMR (DMSO-de): 5 9.57 (s, C3-OH), 7.3-7.16 (m, 5 arom. ), 6.67 (s, 2 arom. H, d-H, C2-H), 4.88 (s, C5-H), 3.56 (s, N*CH3, axial), 3.21 (s, *NCH3, quatorial); MS (CI): m/z 434 (M+). xample 37 ynthesisof (17S)-4,5a-epoxy-17-ethyl-3-hydroxy-17-methyl-6-oxo-14B-[(3- lienylpropyl)oxy]morphinanium-iodide (compound 39). A solution of compound 20 (see Example 20) (250 mg, 0.58 mmol) and methyl iodide (0.36 ml, 5.80 mmol) in acetonitrile (10 ml) was stirred for 6 days at 50"C (bath temperature) under N2. The solution was evaporated down and the evaporation residue (320 mg of bright beige foamy resin) was purified using column chromatography (silica gel; CH2CI2I MeOH: each 11: (9515), (92.5 / 7.5)). Evaporation residue (240 mg, 72%) of amorphous compound 39. Fp. 171-176°C; IR (KBr): 1723 (C=0) cm"1; 1H-NMR (DMSO-d6): 6 9.55 (s, C3-OH), 7.31-7.16 (m, 5 arom. H), 6.68 (s, 2 arom. H, C,-H, C2-H), 4.87 (s, C6-H), 3.44 (3 H, N+CH3, axial), 1.34 (t, 3 H, 'NCH,CI-k J = 7 Hz); MS (CI): m/z 448 (M*). Example 38 Synthesis of (17R)-4,5a-epoxy-3-hydroxy-17-methyl-6-oxo-14B-[(3-phenylpropyl)oxy]-17-[(2-R,S-tetrahydrofurfuran-2-yl)methyl]morphinanium-iodide (compound 40). Compound 40 A solution of the compound 10 (see Example 10) (190 mg, 0.39 mmol) and methyl iodide (0.24 ml, 3.9 mmol) in acetonitrile (8 ml) was stirred for 10 days at 40-50X (bath temperature) under N2. The solution was evaporated down and the evaporation residue (248 mg of beige foamy resin) was purified using column chromatography (silica gel; CH2CI2/ MeOH: 2 I: (250 / 5); 1 I: (250 / 7.5)). The resulting evaporation residue (70 mg of yellow foamy resin, 28%) was pure compound 40. Fp. 156-159°C; IR (KBr): 1724 (CO) cm"1; 1H-NMR (DMSO-d6): 5 9.53 (s, C3-OH), 7.30-7.16 (m, 5 arom. H), 6.68 (s, 2 arom. H, d-H, C2-H), 4.85 (s, 1 H, Cs-H), 3.58 (s, +NCH3, axial); MS (CI): m/z 504 (M*). Example 39 Synthesis of (17R)-17-altyl-4,5a-epoxy-H3-ethoxy-3-hydroxy-17-methyl-6-oxomorphinanium-iodide (compound 41). Compound 41 A solution of 14-O-ethylnaloxone (Kobylecki et al., J. Med. Chem. 1982, 25, p. 116) (300 mg, 0.84 mmol) and methyl iodide (0.25 ml, 4.2 mmol) was stirred in 8 ml acetonitrile for 7 days at 30°C (bath temperature) and then evaporated down. The evaporation residue (450 mg of light brown oil) was purified using column chromatography (silica gel; CH2CI2 / MeOH (250:4)). Evaporation residue (110 mg, 35%) of amorphous compound 41. Fp. 130-134°C; IR (KBr): 1724 (CO) cm"1; 1H-NMR (DMSO-d6): 5 9.54 (s, C3-OH), 6.70 (s, 2 arom. H), 6.32-6.07 (m, 1 olef. H), 5.84-5.63 (m, 2 olef. H), 4.92 (s, C5-H), 3.49 (s, +NCH3, axial), 1.24 (t, 3 H, OCH?Chk J = 6.8 Hz); MS (CI): m/Z 370 (M*). Example 40 Synthesis of (17R)-17-allyl-4,5Q-epoxy-3-hydroxy-143-methoxy-17-methyl-6-oxomorphinanium- iodide (compound 42). Compound 42 A solution of 14-O-methylnaloxone (Kobylecki etal., J. Med. Chem. 1982, 25, p. 116) (230 mg, 0.67 mmol) and methyl iodide (0.21 ml, 3.37 mmol) was stirred in 10 ml acetonitrile for 7 days at 40"C (bath temperature) and then evaporated down. The evaporation residue (341 mg of light brown oil} was purified using column chromatography (silica gel; CH2CI2/ MeOH (250:4.5 -> 250:9)). Evaporation residue (202 mg, 62%) of amorphous compound 42. Fp. 178-181°C; IR(KBr): 1722 (CO) cm'1; 1H-NMR (DMS0^6): 5 9.55 (s, C3-OH), 6.70 (s, 2 arom. H), 6.28-6.06 (m, 1 olef. H), 5.82-5.64 (m, 2 olef. H), 4.94 (s, C5-H), 3.45 (s, *NCH3, axial), 3.38 (s, CH30); MS (CI): m/z 356 (M+). Example 41 Synthesis of (17S)-17-allyl-4,5a-epoxy-3-hydroxy-14i3-methoxy-17-methyl-6HDxomorphinanium- iodide (compound 43). A solution of 14-0-methyloxymorphone(Schmidhammeretal., J. Med. Chem. 1984, 27, pp. 1575-1579) (210 mg, 0.67 mmol) and allyl iodide (0.28 ml, 3.35 mmol) was stirred in 5 ml N,N-dimethylformamide for 7 days at 40°C (bath temperature) and then evaporated down. The evaporation residue (484 mg of brown oil) was purified using column chromatography (silica gel; CH2CI2/ MeOH (250:5 -> 250:12)). The evaporation residue (134 mg)was again purified using column chromatography (silica gel; CH2CI2/ MeOH (250:4.5)). Evaporation residue 77 mg (27%) of amorphous compound 43. Fp. >140°C; IR (KBr): 1724 (CO) cm-1; 1H-NMR (DMSO-d6): 6 9.57 {s, C3-OH), 6.68 (s, 2 arom. H), 6.28-6.08 (m, 1 olef. H), 5.75-5.63 (m, 2 olef. H). 4.95 (s, C5-H), 3.42 (s, CH30), 3.05 (s, *NCH3, equatorial); MS (CI): m/z 356 (M*). Example 42 Synthesis of 4,5a-epoxy-3-hydroxy-143-methoxy-17,17-dimethyl-6-oxomorphinanium-iodide {compound 44). Compound 44 A solution of 14-O-methyloxymorphone (Schmidhammeretal., J. Med. Chem. 1984, 27, pp. 1575-1579) (200 mg, 0.63 mmol) and methyl iodide (0.32 ml, 5.07 mmol) in acetonitrile (10 ml) was stirred for 21 hours under N2at50"C (bath temperature). Then methyl iodide (0.2 ml, 3.17 mmol) was again added, stirred further for 24 h under the same conditions and evaporated down. The evaporation residue (324 mg of brown foamy resin) was crystallised out of MeOH (0.5 ml) and purified by recrystallisation out of MeOH. Yield: 244 mg (84%) of compound 44. Fp. 225-240°C; IR (KBr): 1725 (C=0) cm"'; 'H-NMR (DMSO-d6): 5 9.55 (s, C3-OH), 6.69 (s, 2 arom. H, C,-H, CrH), 4.94 (s, C5-H), 3.55 (s, +NCH3, axial), 3.38 (s, OCH3), 3,22 (s, +NCH3, equatorial); MS (CI): m/z 330 (M*). Example 43 Synthesis of 5p-benzyi-14B-(butyloxyH,5a-epoxy-3-hydroxy-17,17-dimethyl-6-oxomorphinanium- iodide (compound 45). Compound 45 NaH {0.52 g, 21.6 mmol) (obtained from 0.86 g of a 60% NaH dispersion in oil by washing with petroleum ether) was added to a solution of 5p-benzyl-14-hydroxycodeinone (M. Gates et al., J, Org. Chem. 1989, 54, pp. 972-974) (2.90 g, 7.2 mmol) in 40 ml water-free N,N-dimethylformamide under N2 at 0°C (bath temperature) under stirring. After 20 min. trans-crotylbromide (1.26 g, 9.3 mmol) was added and the mixture first stirred for 40 min at 0°C (bath temperature), then for 2 h at room temperature. Then small pieces of ice were added until no more hydrogen was given off, the reaction mixture was poured onto 100 ml water and extracted with dichloromethane (1 x 100 ml, 5 x 50 ml). The combined organic phases were washed with saturated sodium chloride solution (6 x 250 ml), dried over sodium sulphate and the evaporation residue (3.25 g of brown oil) purified using column chromatography (silica gel; CH2CI2/ MeOH / cone. NhUOH 250 : 6 : 0.5). From the resulting yellowish oil (1.86 g, 56%) 0.1 g was dissolved in 5 ml ether and etherial HCI added. 0.1 g of colourless crystals of 5p-benzyl-143-{[(E)-(but-2-enyl]oxy}-7,8a-didehydro-4,5a-epoxy-3-methoxy-17-methylmorphinan-6-one hydrochloride was isolated. Fp. 125-1308C; MS (CI): 458 (M*+1); IR (KBr): 1684 (C^OJcm"1; 1H-NMR (DMSO-d6, 6 in ppm): 9.22 (s, wide HN*)T 7.28-7.13 (m, 5 arom. H; 1 olefin. H, CH-8), 6.84 (d, 1 arom. H, J = 8.4 Hz), 6.74 (d, 1 arom. H, J = 8.4 Hz), 6.23 {d, 1 olefin. H, CH-7, J = 10.2 Hz), 5.69-5.34 (m, 2 olefin. H), 3.75 (s, CH30), 2.91 (d, CH3N+), 1.69-1.65 (d, 3 H, C14-OCH2CHCHCHa, J = 7.4 Hz). A mixture of 5p-benzyl-14p-{[(E)-(t>ut-2-enyl]oxy}-7,8-didehydro-4,5a-epoxy-3-methoxy-17-methylmorphinan-6-one (1.75 g, 3.8 mmol) and 0.24 g Pd/C (10%) in 60 ml methanol was hydrogenated for 1.5 hours at 35 psi and room temperature. The catalyst was filtered off and washed with 20 ml methanol. The filtrate was evaporated down. Yield: 1.43 g (81%) of bright yellow oil of which 0.1 g was dissolved in 5 mt ether and the hydrochloride was precipitated by the addition of etherial HCI. 0.1 g of colourless crystals of 5B-benzyl-14B-(butoxy)-4,5a-epoxy-3-methoxy-17-methylmorphinan-6-one hydrochloride was isolated. Fp. 148-152°C; MS (CI): 462 (M*+1); IR (KBr): 1729 (C=0) cm-1; 1H-NMR (DMSO-d8, 6 in ppm): 9.00 (s, wide HN*), 7.29-7.16 {m, 5 arom. H); 6.85 (d, 1 arom. H, J = 8.4 Hz), 6.75 (d. 1 arom. H, J = 8.4 Hz), 3.80 (s, CH30), 2.94 (d, CH3N*, J = 4.4 Hz), 1.02 (t, 3H, C14-0(CH2)3CH3, J = 7.2 Hz). A solution of 5B-benzyl-14B-butoxy-4,5a-epoxy-3-methoxy-17-methylmorphinan-6-one (1.30 g, 2.82 mmol) in 10 ml 48% HBrwas reflux heated for 20 min. Then the solution was cooled, poured onto 100 ml of ice, alkalised with cone. NH4OH and extracted with dichloromethane (5 x 50 ml). The combined organic phases were washed with saturated sodium chloride solution (3 x 150 ml), dried over sodium sulphate and evaporated down. The residue (0.97 g of grey-black foamy resin) was purified using column chromatography (silica gel; CHjC^ / MeOH / cone. NH4OH 250 : 6 : 0.5). Yield: 0.82 g (65%) of dark yellow oil of which 0.06 g was dissolved in 5 ml ether and the hydrochloride precipitated by the addition of etherial HCI. 0.06 g of beige crystals of 5B-benzyl-143-butoxy-4,5a-epoxy-3-hydroxy-17-methylmorphinan-6-one hydrochloride was isolated. Fp. 200-204"C; MS (CI): 448 (M++1); IR (KBr): 1729 (C=0) cm'1; 'H-NMR (DMSO-d6, 5 in ppm): 9.45 (s, OH), 8.72 (s, wide HN*), 7.25-7.22 (m, 5 arom, H); 6.67-6.63 (s, 2 arom. H, CH-1 and CH-2), 2.93 (d, CH3N*), 1.02 (t, 3H, C14-0(CHa)3CJH3, J - 7.3 Hz). A solution of 5(3-benzyl-14B-butoxy-4,5a-epoxy-3-hydroxy-17-methylmorphinan-6-one (0.32 g, 0.72 mmol) and methyl iodide (0.51 g, 3.58 mmol) in 10 ml of water-free acetonitrile was stirred under N2 at 40°C (bath temperature) for 2 days and then evaporated down. The evaporation residue (0.41 g of brown oil) was purified using column chromatography (silica gei; GH£\2! MeOH 250 :6). Yield: 0.22 g (54%) slightly beige crystals of the compound 45. Fp. 18S-195°C; MS (CI): 462 (M+); IR (KBr): 1729 (C=0) cm"1; 1H-NMR (DMSO-d6, 6 in ppm): 9.49 (s, OH), 7.28-7.20 (m, 5 arom. H), 6.69 (d, 1 arom. H, J = 8.2 Hz), 6.62 (d, 1 arom. H, J = 8.2 Hz), 3.61 (s, CH3N\ axial), 3.23 (s, CH3N*, equatorial), 1.01 (t, 3 H, C^-OtCH^CHa, J = 7.0 Hz). Example 44 Synthesis of {17S)-17-allyl-5p-benzyt-14B-butoxy-4,5a-epoxy-3-hydroxy-17-methyl-6- oxomorphinanium-iodide (compound 46). Compound 46 A solution of 5p-benzyl-14p-butoxy-4,5a-epoxy-3-hydroxy-17-methylmorphinan-6-one (see Example 45) (0.31 g, 0.69 mmol) and allyl bromide (0.94 g, 5.59 mmol) in 10 ml of water-free acetonitrile was stirred under N2 at 40°C (bath temperature) for one day and then evaporated down. The evaporation residue (0.45 g of brown oil) was purified using column chromatography (silica gel; CH2CI2/MeOH 250 : 5). Yield: 0.11 g (26%) of beige crystals of the compound 46. Fp. 200-205°C; MS (CI): 488.2 (M*); IR (KBr): 1728 (C=0) cm'1; 1H-NMR (DMSO-d6, 5 in ppm): 9.49 (s, OH), 7,26-7.23 (m, 5 arom. H), 6.67 (s, 2 arom. H, CH-1 and CH-2), 6.22-6.13 (m. 1 olefin. H), 5.80-5.66 (m, 2 olefin. H), 3.50 (s, CH3N*. equatorial), 1.02 (t, C14-0(CH2)3CH3, J = 7.4 Hz). Example 45 Synthesis of 143-butoxy-4,5a-epoxy-3-hydroxy-17,17-dimethyl-6-oxomorphinanium-iodide (compound 47) NaH (0.92 g, 38.3 mmol) (obtained from 1.53 g of a 60% NaH dispersion in oil by washing with petroleum ether) was added to a suspension of 14-hydroxycodeinone (lijima et al., J. Med. Chem. 1978, 21, p. 398) (4.0 g, 12.8 mmol) in 50 ml water-free N,N-dimethylformamide under N2 at 0"C (bath temperature) under stirring. After 20 min. trans-crotylbromide (2.24 g, 16.6 mmol), dissolved in 20 ml DMF. was added drop by drop and the mixture stirred further for 40 min at 0°C (bath temperature), then for 3 h at room temperature. Then small pieces of ice were added until no more hydrogen was given off, the mixture was poured onto 100 ml water and extracted with dichloromethane (1 x 100 ml, 5 x 50 ml), the combined organic phases were washed with saturated sodium chloride solution (6 x 250 ml) and dried over sodium sulphate. The evaporation residue (5.2 g of yellow-brown oil) was purified using column chromatography (silica gel; CH2CI2 / MeOH / cone. NH4OH (250 : 5: 0.5)). A yellowish oil (2.20 g) was produced which was crystallised out of methanol. Yield: 1.75 g (36%) of yellowish crystals of 14B-{[{EHbut-2-enyl]oxy}-7,8-didehydro-4,5a-epoxy-3-methoxy-17-methylmorphinan-6-one. Fp. 113-117°C; MS (CI): 368.2 (M*+1); IR (KBr): 1679 (C=0) cm-1; ^-NMR (DMSO-de, 6 in ppm): 7.13 (d, 1 olefin. H; CH-8, J = 10.0 Hz), 6.73 (d, 1 arom. H, J = 8.0 Hz), 6.64 (d, 1 arom. H, J = 8.0 Hz), 6.14 (d, 1 olefin. H, CH-7, J = 9.8 Hz), 5.69-5.43 (m, 2 olefin. H), 4.78 (s, CH-5), 4.03-3.80 (m, 2H, C14-OCH2-), 3.72 (s, CH30), 2.34 (s, CH3N'), 1.64 (d, OCH2CHCHCHj, J = 6.0 Hz). A mixture of 143-{[(E)-(but-2-enyl]oxy}-7,8a-didehydro-4,5a-epoxy-3-methoxy-17-methylmorphinan-6-one{0.82g, 2.23 mmol) and 0.82 g Pd/C (10%) in 50 ml methanol was hydrogenatedfor45 min. at 30 psi and at room temperature. The catalyst was filtered off, washed with 20 ml methanol and the filtrate evaporated down. Yield: 1.02 g of bright yellow oil, which was purified using column chromatography (silica gel; CH2CI2/ MeOH / cone. NH4OH (250 : 2 : 0.5)). This gave a yellowish oil which was crystallised out of methanol. Yield: 0.52 g (63%) of colourless crystals of 14B-butoxy- 4,5a-epoxy-3-methoxy-17-methylmorphinan-6-one was isolated. Fp. 112-117"C; MS (CI): 371.1 (M*+1); IR (KBr): 1722 (C=0) cm'1; 1H-NMR (DMSO-d6, 5 in ppm): 6.74 {d, 1 arom. H, J = 8.0 Hz), 6.65 fd, 1 arom. H, J = 8.2 Hz), 4.75 (s, CH-5), 3.78 (s, CH30), 2.29 (s, CH3N), 0.93 ft, OCHjCh^CHsCHj, J = 7.2 Hz). A solution of 14p-butoxy-4,5a-epoxy-3-methoxy-17-methylmorphinan-6-one (0.30 g, 0.81 mmol) in 3.2 ml 48% HBr was reflux heated for 8 min. Then the solution was cooled, poured onto 20 ml of ice, alkalised with cone. NH4OH and extracted with dichioromethane (5 x 30 ml). The combined organic phases were washed with saturated sodium chloride solution (3 x 100 rnl), dried over sodium sulphate and evaporated down. The residue (0.29 g of brown oil) was purified using column chromatography (silica gel; CH;CI2/ MeOH / cone. NH4OH 250 : 5 : 0.5). Yield: 0.06 g (21%) of dark yellow oil which was dissolved in 5 ml ether and converted into the hydrochloride with etherial HCI. 0.06 g of light brown crystals of 14P-butoxy-4,5a-epoxy-3-hydroxy-17-methylmorphinan-6-one hydrochloride was isolated. Fp. 168-172°C; MS (CI): 358.2 (M*+1); IR (KBr): 1725 (C=0) cm-1; 1H-NMR (DMSO-do, 5 in ppm): 9.51 (s, OH), 8.75 (s, wide, HN+), 6.71 {d, 1 arom. H, J = 8.2 Hz), 6.65 (d, 1 arom. H, J = 8.0 Hz), 4.92 (s, CH-5), 2.82 (d, CH3N\ J = 4.4 Hz), 0.95 (t, 0(CH2)3Ctl3, J = 7.4 Hz). A. solution of 14B-butoxy-4,5a-epoxy-3-hydraxy-17-methylmorphinan-6-or\e (0.53 g, 1.49 mmof) artd methyl iodide (1.06 g, 7.44 mmoi) in 10 ml of water-free acetonitrile was stirred under N2 at 40"C (bath temperature) for 2 days and then evaporated down. The evaporation residue (0.70 g of brown oil) was purified using column chromatography (silica gel; CH2CI2/ MeOH 250 : 4). Yield: 0.31 g (42%) of colourless crystals of the compound 47. Fp. 180-185°C; MS (CI): 372.2 (M*); IR (KBr): 1726 (C=0) cm'1; 1H-NMR (DMSO-d6, 5 in ppm): 9.55 (s, OH), 6.68 (s, 2 arom. H), 4.95 (s, CH-5), 3.57 (s, CH3N*, axial), 3.21 (s, CH3N+, equatorial), 0.94 (t, 0(CH2)3CH3, J = 7.3 Hz). Example 46 Synthesis of (17R)-17-cyclopropylmethyl-4,5a-epoxy-3-hydroxy-17-methyl-6-oxo-14B-[(3-phenylpropyl)oxy]morphinanium-iodide (compound 48) and of (17R)-17-cyclopropylmethyl-4,5a-epoxy-3-methoxy-17-methyl-6-oxo-14B-[(3-phenylpropyl)oxy]morphinanium-iodide (compound 49). A mixture of 17-cyclopropylmethyl-4,5a-epoxymorphinan-6-spiro-2'-(1.3-dioxolane)-3,14p-diol {Schmidhammer et al., Heterocycles 1998, 49,1, pp. 489-498) (7.92 g, 20.55 mmol), K2CO3 (7.67 g, 55.49 mmol), benzyl bromide (4.57 g, 26.72 mmol) and 80 ml of water-free N,N-dimethyiformamide was stirred for 12 h under N2 at room temperature. The inorganic material was filtered off, washed with dichloromethane and the filtrate evaporated down. The crystalline evaporation residue (10.97 g) was recrystallised out of methanol. Yield: 8.80 g (90%) of colourless crystals of 3-benzyloxy-17-cyclopropylmethyl-4,5a-epoxy-143-hydraxymorphinan-6-spiro-2'-(1,3-dioxolane). Fp. 130-131"C; MS (CI): 476 (lvf+1); IR (KBr): 3352 (OH) cm"1; 1H-NMR (CDCl3, 5 in ppm): 7.42-7.27 (m, 5 arom. H), 6.75 (d, 1 arom. H, J = 8.3 Hz), 6.54 (d, 1 arom. H, J = 8.3 Hz), 5.17 (d, 1H, J = 11.7 Hz, OCH2Ph), 5.10 (d, 1H, J = 11.7 Hz, OCH2Ph), 4.58 (s, CH-5), 4.19-3.73 (m, 4H, OCH2CH20). NaH (2.24 g, 93.6 mmol) (obtained from 3.75 g of a 60% NaH dispersion in oil by washing with petroleum ether) was added to a solution of 3-benzyloxy-17-cyclopropylmethyl-4,5a-epoxy-14J3-hydroxymorphinan-6-spiro-2'-(1,3-dioxolane) (14.8 g, 31.2 mmol) in 100 ml water-free N,N-dimethylformamide under N2 at 0"C (bath temperature) under stirring. After 20 min. ctnnamyl bromide (7.99 g, 40.6 mmol), dissolved in 20 ml DMF, was added drop by drop and the mixture stirred further for 25 min at 0°C (bath temperature), then for 3.5 h at room temperature. Then small pieces of ice were added until no more hydrogen was qiven off. The mixture was poured onto 200 ml water and extracted with dichloromethane (4 x 100 ml), the combined organic phases were washed with saturated sodium chloride solution (5 x 250 mi), dried over sodium sulphate and evaporated down. The evaporation residue {18.2 g of yellow-brown oil) was purified using column chromatography (silica gel; CHZCI2/ MeOH / cone. NH4OH 250 : 3 : 0.5). A yellowish oil (6.1 g, 33%) was produced of which 0.2 g was dissolved in 5 ml ether and converted into the hydrochloride with etherial HCI. 0.1 g of beige crystals of 3-benzyloxy-17-cyclopropylmethyl-4,5a-epoxy-14p-{[(E)-3-phenylprop-2-enyl]oxy}morphinan-6-spiro-2'-(1,3-dioxolane) hydrochloride was isolated. Fp. 133-136°C; MS (CI): 592 (M*+1); 'H-NMR (DMSO-d6): 6 8.23 (s, wide. HN*), 7.63-7.24 (m, 10 arom. H), 6.93 (d. 1 arom. H, J = 8.4 Hz), 6.70 (d, 1 arom. H, J = 8.4 Hz), 6.70 (m, 2 olefin. H), 5.15 (s, 2H, C3-OCHgPh), 4.65 (s, CH-5), 4.33-4.20 (m, 2H, OChbCHCHPh), 4.04-3.74 (m, 4 H, OCH2CH2). A mixture of 3-benzyloxy-17-cyclopropylmethyl-4,5a-epoxy-148-{[(E)-3-phenylprop-2-enyl]oxy}morphinan-6-spiro-2'-(1,3-dioxolane) (6.08 g, 10.3 mmol) and 0.60 g of Pd/C (10%) in a mixture of 100 ml methanol and 50 ml tetrahydrofuran was hydrogenated for 2.5 hours at 30 psi and at room temperature. The catalyst was filtered off, washed with 20 ml each of methanol and tetrahydrofuran and the filtrate evaporated down. Evaporation residue 4.02 g of bright yellow oil, which was purified using column chromatography (silica gel; CH2CI2/ MeOH / cone. NH40H 250 : 5 : 0.5). This gave a yellowish oil (2.75 g, 53%) of which 0.07 g was dissolved in 5 ml ether and converted into the hydrochloride with etherial HCI. 0.06 g of colourless crystals of 17-cyclopropylmethyl-4,5Q-epoxy-3-hydroxy-14B-[(3-pheny!propyl)oxy]morphinan-6-spiro-2'-(1,3-dioxolane) hydrochloride was isolated. Fp. 158-162°C; MS (CI): 504 (M*+1); 1H-NMR (DMSO-d6, 5 in ppm): 9.24 (s, OH), 7.79 (s, wide, HN*), 7.35-7.18 (m, 5 arom. H), 6.68 (d, 1 arom. H, J = 8.0 Hz), 6.57 (d, 1 arom. H, J = 8.0 Hz), 4.51 (s, CH-5), 4.09-3.71 (m, 4H, OCH2CH20). A solution of 17-cyclopropylmethyl-4,5a-epoxy-3-hydroxy-14p-[(3-phenylpropyl)oxy]morphinan-6-spiro-2'-(1,3-dioxolane) (0.22 g, 0.44 mmol) was reflux heated for 1 h in 5 ml of a mixture of cone. HCI / MeOH (4:9). After cooling the resulting crystals were filtered off, the filtrate evaporated down and the residue crystallised out of ether. Yield: 0.122 g (61%) of colourless needle-shaped crystals of 17-cyclopropylmethyl-4,5a-epoxy-3-hydroxy-143-[(3-phenylpropyl)oxy]morphinan-6-one hydrochloride. Fp. 200-230°C; MS (CI): 460.3 (M*+1); IR (KBr): 1725 (CO) cm*1; 1H-NMR (DMSO-d6, 6 in ppm): 9.52 (s, OH), 8.20 (s, wide, HN*), 7.30-7.18 (m, 5 arom. H), 6.71 (d, 1 arom. H, J = 8.0 Hz), 6.64 (d, 1 arom. H, J = 8.0 Hz), 4.89 (s, CH-5). A solution of 17-cyclopropylmethyl-4,5a-epoxy-3-hydroxy-14p-[(3-phenylpropyl)oxy]morphinan-6-one (0.54 g, 1.17 mmol) and methyl iodide (0.83 g, 5.84 mmol) in 10 ml of water-free acetonitrile was stirred under N2 at 40"C (bath temperature) for 5 days and then evaporated down. The residue (0.72 g of brown oil) was purified using column chromatography (silica gel; CH2CI2/ MeOH 250 :4). Two different products were isolated: Compound 48: Yield: 0.21 g (30%) of colourless crystals. Fp. 175-176°C; MS (CI): 474 (M*); IR (KBr): 1726 (C=0) cm"1; 1H-NMR (DMSO-d6, 8 in ppm): 9.53 (s, wide, OH), 7.31-7.17 (m, 5 arom. H), 6.69 (s, 2 arom. H), 4.87 (s, CH-5), 3.53 (s, CH3N*. axial). Compound 49: Yield: 0.03 g (4%) of bright orange crystals. Fp. 133-136°C; MS (CI): 488 (M*); IR (KBr): 1725 (C=0) cm"1; 1H-NMR (DMSO-d6, 5 in ppm): 7.31-7.19 (m, 5 arom. H), 6.89 (d, 1 arom. H, J = 8.4 Hz), 6.82 (d, 1 arom. H, J = 8.4 Hz), 4.94 (s, CH-5), 3.81 (s, C3-OCH3), 3.55 (s, CH3Naxial). Example 47 Synthesis of (17R)-17-cycloprapylmethyl-4,5a-epoxy-3-hydroxy-17-methyl-6-oxo-146-[(2- phenylbenzyl)oxy]morphinanium-iodide (compound 50). Compound 50 NaH (1.51 g, 62.9 mmol) (obtained from 2.51 g of a 60% NaH dispersion in oil by washing with petroleum ether) was added to a solution of 3-benzyloxy-17-cyclopropylmethyl-4,5a-epoxy-14j3-hydroxymorphtnan-6-spiro-2'-(1,3-dioxolane) (see Example 46) (5.99 g, 12.6 mmol) in 75 ml water-free N,N-dimethylformamide under N2 at 0°C (bath temperature) under stirring. After 20 min. 2-phenylbenzyl bromide (4.04 g, 16.4 mmol) was added and the mixture stirred for 20 min at 0"C (bath temperature), then for 2 h at room temperature. Then small pieces of ice were added until no more hydrogen was given off, the mixture was poured onto 200 ml water and extracted with dichloromethane {1 x 100 ml, 2 x 75 ml), the combined organic phases were washed with water (5 x 300 ml) and saturated sodium chloride solution (1 x 100 ml), dried over sodium sulphate and evaporated down. From the evaporation residue (7.90 g of brown oil) 3.52 g were purified using column chromatography (silica gel; CH2Cl2/ MeOH / cone. NhUOH 250 : 2.5 : 0.5). A yellowish oil (2.83 g) was produced which was dissolved in 15 ml ether and converted into the hydrochloride with etherial HCI. In this way 2.20 g of colourless crystals of 3-benzyloxy-17-cyclopropylmethyl-4,5a-epoxy-14p-[(2-phenylbenzyl)oxy]morphinan-6-spiro-2'-(1,3-dioxolane) hydrochloride was obtained. Fp. 142-144flC; MS (CI): 642 (M*+1); 'H-NMR of the purified base (DMSO-d6): 5 7.70-7.25 (m, 14 arom. H), 6.76 (d, 1 arom. H, J = 8.4 Hz), 6.53 (d, 1 arom. H, J = 8.4 Hz), 5.10 (s, 2H, C3-OCH2Ph), 4.63 (d, 1H, CH-OCHg, J = 10.6 Hz), 4.46 (s, CH-5), 4.34 (d, 1H, CH-OCH2, J = 10.6 Hz), 4.10-3.69 (m, 4H,OCH2CH20). A solution of 3-benzyloxy-17-cyclopropylmethyl-4,5a-epoxy-14B-[(2-phenylbenzyl)oxy]morphinan-6-spiro-2'-(1,3-dioxolane) hydrochloride (2.10 g, 3.10 mmol) in 40 ml of a mixture of cone. HCI / MeOH (4:9) was reflux heated for 1.5 h. After cooling the mixture was poured onto 100 ml of ice, alkalised with cone. NH4OH and extracted with dichloromethane (1 x 100 ml, 4 x 75 ml), the combined organic phases washed with water (2 x 150 ml) and a saturated sodium chloride solution (1 x 100 ml), dried over sodium sulphate and evaporated down. A yellow oil (1.90 g) was obtained, which was purified using column chromatography (silica gel; CH2CI2/ MeOH / cone. NH4OH (250 : 3 : 0.5)). This gave a yellowish oil (0.7 g, 42%) of which 0.16 g was dissolved in 5 ml ether and converted to the hydrochloride with etherial HCI. 0.12 g of colourless crystals of 17-cyclopropylmethyl-4,5a-epoxy-3-hydroxy-14BB-[(2-phenylbenzyl)oxy]morphinan-6-one hydrochloride was isolated. Fp. 181-186"C; MS (CI): 508 (M*+1); |R (KBr): 1725 (C=0) cm'1; 'H-NMR (DMSO-d6, 6 in ppm): 9.58 (s, OH), 8.33 (s, wide, HN*), 7.95-7.25 (m, 9 arom. H), 6.72 (d, 1 arom. H, J = 8.0 Hz), 6.64 (d, 1 arom. H, J = 8.0 Hz), 5.14 (s. CH-5), 4.84 (d, 1H, CU-OCHj-R. J = 12.4 Hz), 4.56 (d, 1H, C14-OCH2-R, J = 12.4 Hz). A solution of 17-cyclopropylmethyl-4,5a-epoxy-3-hydroxy-146-[(2-phenylbenzyl)oxy]morphinan-6-one (0.39 g, 0.76 mmol) and methyl iodide (0.54 g, 3.79 mmol) in 6 ml of water-free acetonitrile was stirred under N2 at 40°C (bath temperature) for 2 days and then evaporated down. The residue (0.5 g of brown oil) was purified using column chromatography (silica gel; CH2CI2 / MeOH 250 :4). Yield: 0.02 g (4%) of beige crystals of the compound 50. Fp. 219-221°C; MS (CI): 522 (M*); IR (KBr): 1725 (C=0) cm"1; 1H-NMR {DMSO-d6}: 5 9.53 (s, OH), 7.68-7.25 (m, 9 arom. H), 6.67 (s, 2 arom. H), 4.73 (d, CI4-OCH2), 4.61 (s, CH-5), 3.26 (s, CH3N+, axial). Example 48 Synthesis of (17R)-14B-[(4-chlorobenzyl)oxy]-17-cyclopropylmethyl-4,5a-epoxy-3-hydroxy-17-methyl-6-oxomorphinanium-iodide (compound 51). Compound 51 NaH (1.28 g, 53.3 mmol) (obtained from 2.13 g of a 60% NaH dispersion in oil by washing with petroleum ether) was added to a solution of 3-(benzyloxy)-17-(cyclopropylmethyl)-4,5a-epoxy-14p-hydroxymorphinan-6-spiro-2'-(1,3-dioxolane) (see Example 48) (5.00 g, 10.6 mmol) in 75 ml water-free N,N-dimethylformamide under N2 at 0"C (bath temperature) under stirring. After 20 min. 4-chlorobenzyl bromide (2.95 g, 14.3 mmol) was added and the mixture first stirred for 30 min at 0°C (bath temperature), then for 1.5 h at room temperature. Then small pieces of ice were added until no more hydrogen was given off, the mixture was poured onto 400 ml water and extracted with dichloromethane (3 x 100 ml), the combined organic phases were washed with water (5 x 400 ml) and saturated sodium chtoride solution (1 x 100 ml), dried over sodium sulphate and evaporated down. The evaporation residue (6.45 g of yellow oil) was crystallised out of methanol. Yield: 4.72 g (75%) of colourless crystals of 3-benzyloxy-14p-[(4-chlorobenzyl)oxy]-17-cyclopropylmethyl-4,5a-epoxymorphinan-6-spiro-2'-(1,3-dioxolane). Fp. 122-125°C; MS (CI): 600 (M*+1); 'H-NMR (DMSO-d6 5 in ppm): 7.53-7.35 (m, 9 arom. H), 6.78 (d, 1 arom. H, J = 8.4 Hz), 6.57 (d, 1 arom. H, J = 8.4 Hz), 5.11 (d, 2 H, Ca-OCJiPh), 4.65 (d, 1H, C4-OCH2, J = 11.2 Hz), 4.23 (s, CH-5), 4.30 (d, 1H, C14-OChb, J = 11.2 Hz), 4.10-3.70 (m, 4H, 0CH2CH2O). A solution of 3-benzyloxy-14p-[(4-chlorobenzyl)oxy]-17-cyclopropylmethyl-4,5a-epoxymorphinan-6-spiro-2'-p ,3-dioxolane) {4.60 g, 7.66 mmol) in 100 ml of a mixture of cone. HCI / MeOH (4:9) was reflux heated for 1.5 h. After cooling the reaction mixture was poured onto 300 ml of ice, alkalised with cone. NH4OH, extracted with dichloromethane (3 x 150 ml), the combined organic phases were washed with water (2 x 150ml) and a saturated sodium chloride solution (1 x 100 ml), dried over sodium sulphate and evaporated down. The evaporation residue (4.86 g of yellow oil) was purified using column chromatography (silica gel; CH2CI2/ MeOH / cone. NH4OH 250 : 3 : 0.5). This gave a yellowish oil (1.18 g, 33%) of which 0.26 g was dissolved in 5 ml ether and converted to the hydrochloride with etherial HCI. 0.23 g of colourless crystals of 14p-[(4-chlorobenzyi)oxy]-17-cyclopropylmethyl-4,5a-epoxy-3-hydroxymorphinan-6-one hydrochloride was isolated. Fp. 195-200°C; MS (CI): 466.1 (M*+1); IR (KBr): 1725 (C=0) cm-1; 1H-NMR (DMSO-d6, 6 in ppm): 9.59 (s, OH), 8.63 (s, wide, HN*), 7.61 (d, 2 arom. H, C14-OCH,Fh-CI, J = 8.4 Hz), 7.47 (d, 2 arom. H, C14-OCHaPh-CI, J = 8.4 Hz), 6.73 (d, 1 arom. H, J = 8.2 Hz), 6.68 (d, 1 arom. H, J = 8.0 Hz), 5.08 (s, CH-5), 4.80 (d, 1 H, C14-OChb, J = 12 Hz), 4.72 (d, 1 H. C14-OC&, J = 12 Hz). A solution of 14p-[(4-chlorobenzyl)oxy]-17-cyclopropylmethyl-4,5a-epoxy-3-hydroxymorphinan-6HDne (0.50 g, 1.07 mmol) and methyl iodide (0.76 g, 5.37 mmol) in 8 ml of water-free acetonitrile was stirred under N2 at 40°C (bath temperature) for 6 days and then evaporated down. The residue (0.56 g of brown oil) was purified using column chromatography (silica gel; CH2CI2/ MeOH 250 : 4). Yield: 0.07 g (11%) of beige crystals of the compound 51. Fp. 214-219°C; MS (CI): 480 (M*); IR (KBr): 1733 (C=0) cm"1; 1H-NMR Example 49 Synthesis of 17(R)-4,5a-epoxy-3-hydroxy-14p-methoxy-17-methyl-6-oxo-17-(2- phenylethyi)morphinanium-iadide (compound 52). 1 Compound 52 Amixtureof4,5a-epoxy-3,14p-dimethoxymorphinan-6-one(Kobyleckietal.,J.Med. Chem., 1982, 25, 2, pp. 116-120) (1.44 g, 4.57 mmol), potassium carbonate (4.11 g, 29.7 mmol), 2-phenylethyl bromide (1.1 g, 5.94 mmol) and 20 ml of N.N-dimethylformamide was stirred for 5.5 h at 80°C (bath temperature) under N2. Then 200 ml of water was added to it and extraction took place with dichloromethane (4 x 50 ml). The combined organic phases were washed with water (6 x 130 ml), dried over sodium sulphate and evaporated down. Yield: 1.95 g of yellowish oil of 4,5a-epoxy-3,140-dimethoxy-17-(2-pheny!ethyl)morphinan-6-one, which was used unmodified for the next synthesis step. Analytical data: 1H-NMR (CDCI3, 5 in ppm): 7.30-7.18 (m, 5 arom. H), 6.69 (d, 1 arom. H, J = 8.0 Hz), 6.60 (d, 1 arom. H, J = 8.0 Hz), 4.64 (s, CH-5). 3.89 (s, C3-OCH3), 3.18 (s, C14-OCH3). A solution of 4,5a-epoxy-3,14S-dimethoxy-17-(2-phenylethyl)morphinan-6-one (2.4 g, 5.72 mmol) in 25 ml of 48% HBrwas reflux heated for 13 min. Then the solution was cooled, poured onto 100 ml of ice, alkalised with cone. NH4OH and extracted with dichloromethane (5 x 50 ml). The combined organic phases were washed with a saturated sodium chloride solution (3 x 150 ml), dried over sodium sulphate and evaporated down. The evaporation residue (2.40 g of brown oil) was purified using column chromatography (silica gel; CH2CI2/ MeOH / cone. NH4OH 250 : 2 : 0.5). Yield: 0.4 g (17%) of dark yellow oil of which 0.04 g was dissolved in 5 ml ether and the hydrochloride obtained with etherial HCI. 0.02 g of colourless crystals of 4,5a-epoxy-3-hydroxy-148-methoxy-17-(2-phenylethyl)morphinan-6-one hydrochloride was isolated. Fp. 259-262sC; MS (CI): 406 (M++1); IR (KBr): 1731 (C=0) cm"1; 'H-NMR (DMSO-d6 5 in ppm): 9.52 (s, OH), 9.28 (s, wide, HN*), 7.38-7.25 (m, 5 arom. H), 6.70 (s, 2 arom. H, CH-1 and CH-2), 4.96 (s, CH-5), 3.40 (s, C14-OCH3). A solution of 4,5a-epoxy-3-hydroxy-l4B-rnethoxy-17-(2-phenylethyl)morphinan-6-one (0.32 g, 0.78 mmol) and methyl iodide (0.56 g, 3.92 mmol) in 6 ml of water-free acetonitrile was stirred under N2 at 40°C (bath temperature) for 2 days and then evaporated down. The residue (0.32 g of brown oil) was purified using column chromatography (silica gel; CH2CI2/ MeOH 250 : 2). Yield: 0.07 g (16%) of colourless crystals of the compound 52. Fp. 180-18TC; MS (CI): 420 (tvf+1); IR (KBr); 1727 (C=0) cm-1; 1H-NMR (D20, 5 in ppm): 7.17-7.14 (m, 5 arom. H), 6.56 (s, 2 arom. H), 5.18 (s, CH-5), 3.64 (s, CH3N\ axial), 3.44 (s, OCH3). Example 50 4,5a-epoxy-17-methyl-14B-[(3-phenylpropyl)oxy]morphinan-6-one (compound 53). Compound 53 Water-free K2C03 (5.67 g, 41.06 mmol) and 5-chloro-1-phenyl-1H-tetrazol (3.02 g, 16.73 mmol) were added to a solution of 4,5a-epoxy-3-hydroxy-'\7-methyl-14fi-[(3-phenylpropy\)oxy}rnorphinan-8-one (see Example 36) (6.38 g, 15.20 ml) in 40 ml of water-free dimethylformamide and this mixture stirred for 23 h at room temperature. After the addition of 300 ml H20, extraction took place with CH2CI2 (3 x 75 ml). The combined organic phases were washed with H20 (2 x 200 ml) and saturated NaCI solution (3 x 250 ml), dried over Na2S04 and evaporated down. The evaporation residue (7.48 g of yellowish oil) was purified using column chromatography (silica gel; CH2CI2 / MeOH / cone. NH4OH (250 : 2 : 0.5)). The appropriate fractions were evaporated down. This gave 6.41 g of yellow oil(4,5a-epoxy-17-methyl-14S-[(3-phenylpropyi)oxy]-3-[(1-phenyl-1H-tetrazo[-5-yl)oxy]morphinan-6-one; 75%), which was used for the next reaction step without further purification. For analytical purposes a small quantity was crystallised out of ether and in this way 4,5a-epoxy-17-methyl-14p-[(3-phenylpropyl)oxy]-3-[(1-phenyl-1H-tetrazol-5-yl)oxy]morphinan-6-one was obtained as colourless crystals. Fp. 117-119°C; MS (CI): 564 (M*+1); IR (KBr): 1723 (C=0) cm-1; 1H-NMR (DMSO-d6): 5 7.88-7.837 (m, 2 arom. H), 7.73-7.62 (m, 3 arom. H). 7.30-7.16 (m, 6 arom. H). 6.85 (d, J = 8.4 Hz, 1 arom. H), 4.93 (s, CH-5), 2.29 ( s, 3 H, N17-CHa). A mixture of 4,5a-epoxy-17-methyl-14p-[{3-phenylpropyl)oxy]-3-[(1-phenyl-1H-tetrazol-5-yl)oxy]morphinan-6-one (6.20 g, 11.00 mmol), 10% Pd/C catalyst (2.48 g) and 100 ml glacial acetic acid was hydrogenated at 50 psi and 40°C for 17 h. After filtering off the catalyst, the filtrate was reduced down to a volume of 30 ml, 150 ml of ice/water mixture was added to it and after alkalising with cone. NH4OH it was extracted with CH2CI2(1 x 100 ml, 3 x 75 ml). The combined organic phases were washed with saturated NaCI solution (4 x 200 ml), dried over Na2SO* and evaporated down. The evaporation residue (4.15 g of yellowish oil, DC pure) was crystallised out of a little methanol and in this way 3.20 g (72%) of the compound 53 was obtained as colourless crystals. Fp. 105-109DC; MS (CI): 404 (M*+1); IR (KBr): 1721 (C=0) cm'1; 'H-NMR (DMSO-d6): 5 7.29-7.16 (m, 5 arom. H), 7.04 (t, J = 8.0 Hz, 1 arom. H), 6.73 (d, J = 8.0 Hz, 1 arom. H), 6.64 (d, J = 8.0 Hz, 1 arom. H), 4.75 (s, 1H, C5-H), 2.28 (s, 3H, NI7-CH3). Example 51 17-(cyclopropylmethylH.5a-epoxy-14p-[(3-phenylpropyl)oxy]morphinan-6nDne hydrochloride (compound 54.HCI). Compound 54.HCI NaHC03 (3.33 g, 39.65 mmol) and 1-chloroethyl chloroformate (4.32 ml, 39.65 mmol) were added to a solution of 53 (3.20 g, 7.93 mmol) in 40 ml of ethanol-free 1,2-dichloroethane. This mixture was stirred for 13.5 h at 60°C (oil bath temperature) under N2. Then filtration took place from the inorganic residue, the residue was washed with ethanol-free 1,2-dichloroethane and the filtrate evaporated down. The evaporation residue (3.7 g of yellow-brown oil, DC-pure) was - without further purification and characterisation - reflux heated in a mixture of 15 ml cone. HCI and 35 ml MeOH for 1 h. The reaction solution was evaporated down and the evaporation residue crystallised out of MeOH / Et20. 2.77 g (82%) of 4,5a-epoxy-143-[(3-phenylpropyl)oxy]morphinan-6-one hydrochloride was isolated. Fp. >225°C (decomposition); MS (CI): m/z 390 (M*+1); IR (KBr): 1729 (CO) cm"1; 1H-NMR (DMSO-dg): 5 9.25 (s, wide. 1H, *HN), 8.11 (s. wide, 1H, *HN), 7.34-7.12 (m, 5 arom. H), 7.16 (t, j = 8.0 Hz, 1 arom. H), 6.85 (d, J = 8.0 Hz, 1 arom. H), 6.77 (d, J = 8.0 Hz, 1 arom. H), 4.96 (s, 1H. C5-H),4.28(ps-d, C9-H). Water-free K2C03(2.13g, 15.40 mmol) and cyclopropylmethyl bromide (0.64 ml, 6.67 mmol) were added to a solution of 4,5a-epoxy-143-[(3-phenylpropyl)oxy]morphinan-6-one hydrochloride (2.36 g, 5.55 mmol) in 20 ml of water-free dimethylformamide under N2. This mixture was stirred at a bath temperature of 80°C under N2. Since a DC check after 7 h showed that the reaction had not yet completely finished, a further 0.50 mi of cyclopropylmethyl bromide (5.24 mmol) was added. After a further hour the reaction had finished and after cooling filtration from the inorganic material took place, the residue was washed with CH2CI2 and the filtrate evaporated down. The evaporation residue was dissolved in 150 ml CH2Cl2, washed with H20 (5 x 150 ml) and saturated NaCI solution (150 ml), dried over Na2S04 and evaporated down. This gave 2.43 g (99%) of 17-(cyclopropylmethyl)-4,5a-epoxy-143-[(3-phenylpropyl)oxy]morphinan-6-one (54) as a yellowish oil which was used for the next reaction without further purification. 0.30 g of the oil was dissolved in ether and after the addition of etherial HCI 0.23 g of 17-(cyclopropylmethyl>-4,5a-epoxy-14S-[(3-phenylpropyl)oxy]morpfiinan-6-one hydrochloride (compound 54.HCI)was isolated as a colourless powder. Fp. 145-150°C; MS (CI): m/z 444 (M*+1); IR (KBr): 1726 (C=0) cm"1; 'H-NMR (DMSO-d6): 6 8.26 (s, wide, 1H), 7.31-7.14 (m, 5 arom. H), 7.18 (t, J = 8.0 Hz, 1 arom. H), 6.85 (d, J = 8.0 Hz, 1 arom. H), 6.78 (d, J = 8.0 Hz, 1 arom. H), 4.96 (s, 1 H, C5-H), 4.55 (ps-d, C9-H), 1.09-1.06 (m, 1 H, N17-CH2CH(CHZ)2), 0.75-0.69 (m, 2 H, N-CH^HfCH^), 0.55-0.42 (m, 2 H, N-CH2CH(Chb)2). Example 52 17-(cyclopropylmethyl)-4-hydroxy-14p-[(3-phenylpropyl)oxy]morphinan-6-one hydrochloride (compound 55.HCI). Compound 55.HCI NH4CI (0.72 g, 13.46 mmol) was added to a reflux boiling solution of 54 (1.2 g, 2.71 mmol) in 50 ml MeOH under stirring. 0.88 g (13,46 mmol) activated zinc powder was added in small portions to this mixture. This mixture was stirred under reflux for 80 min., then cooled to room temperature and filtered off from the inorganic residue. The inorganic residue was washed with hot methanol and the filtrate evaporated down. 50 ml H20 was added to the evaporation residue which was then alkalised with cone. NH4OH. This mixture was extracted with CH2CI2 (3 x 80 ml), the combined organic phases washed with saturated NaCI solution (5 x 100 ml), dried over Na2S04 and evaporated down.1.20 g (99%) of 17-(cyclopropylmethyl)-4-hydroxy-14B-[(3-phenylpropyl)oxy]morphinan-6-one (55) was obtained as a yellowish oil which was used for the next reaction step without further purification. For analytical purposes 0.08 g of the oil was dissolved in ether and after the addition of etherial HCI 0.059 g of 17-(cyclopropylmethyl)-4-hydroxy-14B-[(3-phenyipropyl)oxy]morphinan-6-one hydrochloride (55.HCI) was isolated as a colourless powder. Fp. >170"C (decomposition); MS (CI): m/z 446 (M++1); IR (KBr): 1709 (C=0) cm"1; 1H-NMR (DMSO-d6): 5 9.82 (s, 1 H, C4-OH), 8.43 (s, wide, 1 H/N17-H), 7.30-7.20 (m, 5 arom. H, C14-0(CH2)3Etl). 7.03 (t, J = 8.0 Hz, 1 arom. H, C2-H), 6.66 (m, 2 arom. H), 4.40 (ps-d, C9-H), 1.09 (m, 1 H, N17-CH2CH(CH2)2), 0.70-0.67 (m, 2 H, N17-CH2CH(CH2)2), 0.52-0.40 (m, 2 H, N17-CH2CH(CH^)2). Example 53 17-(cyclopropylmethyl>-4-niethoxy-14B-[(3-phenylpropyl)oxy]morphinan-6-one hydrochloride (56.HCI). Compound 56.HCI Water-free K2CQ3 (0.37 g, 2.69 mmol) and 0.46 g (2.69 mmol) of phenyltrimethyl ammonium chloride were added to a solution of 55 (0.40 g, 0.90 mmol) in 6 ml of water-free dimethylformamide under N2. This mixture was stirred for 3.5 h at a bath temperature of 80°C under N2. After cooling filtration from the inorganic material took place, the residue was washed with CH2CI2 and the filtrate evaporated down. The evaporation residue was dissolved in 100 ml CH2CI2, washed with saturated NaCI solution (4 x 150 ml), dried with Na2S04 and evaporated down. The evaporation residue (0.30 g)was purified using column chromatography (silica gel; CH2CI2/ MeOH/conc. NH4OH (250/4/ 0.5)) and the appropriate fractions evaporated down. The evaporation residue (0.23 g) was dissolved in ether and after the addition of etherial HCI, 0.22 g (48%) of the compound 56.HCI was isolated as a colourless powder. Fp. 121-126X; MS (CI): m/z460 (M*+1); IR (KBr): (C=0) 1710 cm" 1; 1H-NMR (DMSO-d6): 6 8.34 (s, wide, 1 H, +N-H), 7.30-7.16 (m, 5 arom. H), 7.22 (t, J = 8.0 Hz, 1 arom. H), 6.88 (d, J = 8.0 Hz, 1 arom. H), 6.82 (d, J = 8.0 Hz, 1 arom. H), 4.42 (ps-d, C9-H), 3.77 (s, 3 H, C4-OCH3), 1.08 (m, 1 H, N-CH2CH(CH2)2), 0.70-0.42 (m, 4 H, N-CHaCH(CH2)A Example 54 4-(n-butoxy)-17-(cyclopropylmethyl}-l4l3-[(3-phenylpropyl)oxy]morphinan-6-one hydrochloride (57.HCI). Compound 57.HCI Water-free K2CO3 (0.55 g, 4.01 mmol) and iodo-butane (0.31 ml, 2.67 mmol) were added to a solution of 55 (0.60 g, 1.34 mmol) in 5 ml of water-free dimethylformamide under N2. This mixture was stirred for 7 h at a bath temperature of 90°C under N2- Then filtration from the inorganic material took place, the residue was washed with CH2CI2 and the filtrate evaporated down. The evaporation residue was dissolved in 100 ml CH2CI2, washed with saturated NaCI solution (3 x 150 ml), dried over Na2SOa and evaporated down. The evaporation residue (0.43 g of brown oil) was purified using column chromatography (silica gel; CH2CI2/ MeOH / cone. NH4OH (250 : 4 : 0.5)) and the appropriate fractions evaporated down. The evaporation residue (0.26 g) was dissolved in ether and after the addition of etherial HCI, 0.19 g (26%) 57.HCI was isolated as a colourless powder. Fp. 172-177°C; MS (CI): mlz 502 (M++1); IR (KBr): (C=0) 1711 cm"1; 'H-NMR (DMSO-d6): 0 8.52 (s, wide, 1 H. *N-H), 7.30-7.15 (m, 6 arom. H), 6.86 (d, J = 8.0 Hz, 1 arom. H), 6.80 (d, J ~ 8.0 Hz, 1 arorn. H), 4.42 (ps-d, C9-H), 3.95 (t, 2 H, J = 6.4 Hz, C4-OCH2 Example 55 Opioid receptor binding studies Opioid receptor binding studies were carried out on rat's brain homogenisates using [3H]DAMGO (u-receptor agonist) as radio-ligand and under strict conformance to an earlier published specification (M. Spetea et at., Neurochemical Research 1998, Vol. 23, pp. 1213-1218). The compounds 8,17,17a 17b, 38,40-43, 48, 49, and 54-56 show very high affinity to u-opioid receptors which are primarily responsible for analgesia (Table 1). All have a clearly higher affinity than the antagonist cyprodime {see H. Schmidhammeret al., J. Med. Chem. 1995, 38, 3071-3077), which is selective to u-opioid receptors. The compounds 8,17,17a 17b, 40,48, and 54-56 show extremely high affinity to u-opioid receptors (in the subnanomolar range). Morphine and the opioid antagonist 3-hydroxycyprodime (see H. Schmidhammer et al., J. Med. Chem. 1995, 36, 3071-3077} show in comparison to these two compounds clearly lower affinity to u-opioid receptors, whereas 14-methoxymetopon exhibits similar affinity. a) "Hot-plate Test" A test on mice ("hot-plate test") was carried out as described earlier (E.L. May et al., J. Med. Chem. 2000; 43, 5030-5036). All tested substances show substantially higher analgesic activity than morphine. The compounds 6-11,17a, 17b and 53 show extremely high analgesic activity which is significantly higher than that of the reference substance 14-methoxymetopon (see 2s. FQrstetal., Eur. J. Pharmacol. 1993; 236: 209-215). Compounds 4 and 32 show in comparison to the compounds 6-11 somewhat lower analgesic activity, because these compounds exhibit an ether function (methoxy group) in Position 3, from which it is known that it reduces the analgesic activity in comparison to the 3-hydroxy analogues. However, the analgesic activity of the compounds 4 and 32 is still surprisingly high. Also, the analgesic activity of the compound 17 with a different ether function (propargyioxy group) in Positron 3 is surprisingly high. b\ "Mouse Tail Flick Test" To determine the analgesic activity of non-quaternised compounds, the "Mouse Tail Flick Test" was carried out as earlier described (E.L. May et al., J. Med. Chem. 2000; 43, 5030-5036), All tested substances show substantially higher analgesic activity than morphine. The compounds 6-8,10,11,17a, 17b and 53 show extremely high analgesic activity which is significantly higher than that of the reference substance 14-methoxymetopon (see Zs. FQrstetal., Eur. J. Pharmacol. 1993; 236: 209-215). Compound 4 shows in comparison to the compounds 6-8,10,11,17a, 17b and 53 a somewhat lower analgesic activity, because this compound exhibits a rnethoxy group in Position 3, from which it is known that it reduces the analgesic activity in comparison to the 3-hydroxy analogues. However, the analgesic activity of compound 4 is surprisingly high. Similarly, compounds 17a and 32, which surprisingly have a very high analgesic activity, have a methoxy group in Position 3. The most active compound in this series, compound 17b, with an EDso (ug/kg, sc) of 0.08, is more active than the most active anafgesically effective substances recognized, etorphine and dihydroetorphine (M.D. Aceto et al., Eur. J. Pharmacol 1997; 338, 215-223). cPRat Tail Flick Test" To determine the analgesic activity of quaternised compounds, a test on rats, the "Rat Tail Flick Test", was used. The test was carried out as described earlier (Zs. Furst et al., Eur. J. Pharmacol. 1993,236,209-215). As quaternary ammonium salts, compounds 38 and 42 show a very high analgesic effect - both are substantially more active than morphine after subcutaneous application (Table 3). Compound 42 is somewhat less active than 14-methoxymetopon after subcutaneous application. After intracerebroventricular application, compound 42 is extremely active, which is an indication that it can overcome the blood-brain barrier only to a limited degree and shows its effectiveness therefore primarily in the periphery (outside of the central nervous system). This goes with a very reduced side-effect rate which is relevant to central side effects such as nausea, vomiting, sedation, dizziness, confusion, respiratory depression and mania. Example 57 Determination of the antagonistic activity Vas Deferens Preparation of the mouse This test was carried out as earlier described using OAMGO (u-receptor agonist) (S. Garadnay et al., Curr. Med. Chem. 2001, 8, 621-626). Compound 48 shows surprisingly very high antagonistic activity to u-opioid receptors, which is unusual for quatemised morphinans (Table 4). Normally quatemised morphinans have a substantially lower activity in comparison to the non-quaternised morphinans. It has substantially higher antagonistic activity than the u-selective opioid receptor antagonist cyprodime. In comparison to naloxone it has a somewhat lower activity, whereas in comparison to 3-hydroxycyprodime it exhibits a somewhat higher activity. Due to its structure as a quaternary ammonium salt, it can only overcome the blood-brain barrier with difficulty and produces its effect mainly in the periphery. Because of this, it can, for example, be used to counter or prevent obstipation or ileus caused by opioids without the analgesia of the administered opioid being cancelled. In comparison to it, naloxone, cyprodime and 3-hydroxycyprodime pass through the blood-brain barrier relatively easily and therefore also cancel the analgesic effect of opioids. WE CLAIM: 1. Compounds of the formula (I) or (la), wherein -{cyclical saturated group) Is either preferably Crdo-cycloalkyl or a heterocycllcal group with 2 to 9 carbon atoms, containing further one or more heteroatoms, with the exception of compounds where Ri Is methyl, Rj is C4-Ct-alkyl, Ra is hydrogen or methyl, R4 is hydroxy or methoxy and Re Is hydroxy, methoxy or an oxygen atom bound to the carbon atom in the 5th position, when X is oxygen; R3: hydrogen, Ct-Ce-alkyl; CrCj-aHtenyi; C7-C1B-ary1alkyl, where aryj is Ca-Cio-aryt and alkyi is Cr Ce-alkyl; Cs-Ci«-arytalkenyl, where aryl is Ca-Cur-aryl and atkenyl Is CrCs-alkenyl; alkoxyalkyl, where alkoxy is d-C-alkoxy and alkyl is d-Cs-alkyt; COj(Ci-Cralkyl); C02H; CH2OH. 3. The compound of the formulas (I) or (1A) as claimed in Claims 1 and 2, in which X ts oxygen; R, is Ci-C«-alkyl; CrCe-alkenyl; C4-C,B-cycioalky1alkyi, where cydoalkyi is Cs-C.o and alkyi is d-Ce; CrCn-aryialkyl, where ar/l is C«-C10-afyl and alkyi is C-Ce-alkyl; R2 Is CrCia-arylalkyI, where aryl is C«- 6. The compound as claimed in Claim 1 or 2, wherein Rs Is OH or alkoxy. 7. The compound as claimed in Claim 1, 2 or 6 wherein R3 Is hydrogen, alkyl or aralkyt, preferably hydrogen or alkyl. 8. The compound as claimed in Claim 1, 2, 6 or 7, wherein R* alkinyloxy. 9. The compound as claimed in Claim 1,2,6, 7 or 8, wherein a single bond Is present between the carbon atoms of the numbers 7 and 8, 10. The compound as claimed in Claim 1,2,6, 7,8 or 9, wherein R2 Is alkyl or aralkyt, preferably aralkyl. 11. The compound as claimed in Claim 1,2,6, 7 , 8. 9 or 10, wherein Ri is alkyl, (cyclical

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