Title of Invention

C7 CARBONATE SUBSTITUTED TAXANES AS ANTITUMOR AGENTS

Abstract

The present invention relates to a taxane having the formula R<SUB>2</SUB> is benzoyloxy ; R<SUB>7</SUB> is R<SUB>7</SUB>aOCOO-; R<SUB>10</SUB> is hydroxy; X<SUB>3</SUB> is C<SUB>1</SUB>-<SUB>8</SUB> alkyl, C<SUB>2</SUB> -<SUB>8</SUB> alkenyl, or heterocyclo ; X<SUB>5</SUB> is-COX<SUB>10</SUB> , wherein X<SUB>10</SUB> is phenyl or C<SUB>2</SUB> -<SUB>8</SUB> alkenyl, or X5 is-COOX<SUB>10</SUB> ,wherein X<SUB>10</SUB> is C<SUB>1</SUB> -<SUB>8</SUB> alkyl; R<SUB>7</SUB> <SUB>a</SUB> is C<SUB>1</SUB> -<SUB>8</SUB> alkyl, phenyl or a 5- or 6-membered heterocyclo; and Ac is acetyl. ABSTRACT IN/PCT/2001/01336/CHE C7Carbenate Substituted Texanes As Antitumor Agents The present invention relates to a taxane having the formula R2 is benzoyloxy ; R7ISR7AOCOO-; R10 is hydroxy ; X3 is C1-8 alkyl, C2-8 alkenyl, or heterocyclo ; X5 is-COXio, wherein X10 is phenyl or C2-8lkenyl, or X5 is-COOX10,wherein X10 is C1-8 alkyl; R7a is C1-8 alkyl, phenyl or a 5- or 6-membered heterocycio; and Ac is acetyl.

Full Text

BACKGROUND OF THE INVENTION The present invention is directed to novel taxanes which have exceptional utility as antitumor agents. The taxane family of terpenes, of which baccatin III and taxol are members, has been the subject of considerable interest in both the biological and chemical arts. Taxol itself is employed as a cancer chemotherapeutic agent and possesses a broad range of tumor-inhibiting activity. Taxoi has a 2'R, 3'S configuration and the following structural fomula: wherein Ac is acetyl Colin et al. reported In U.S. Patent 4,814,470 that certain taxol analogs have an activity significantly greater than that of taxoi. One of these analogs, commonly refered to as docetaxei, has the following structural formula: Although taxol and docetaxei are useful chemotherapeutic agents, there are limitations on their effectiveness, including limited efficacy against certain types of cancers and toxicity to subjects when administered at various doses. Accondingly, a need remains for additional chemotherapeutic agents with improved efficacy and less toxicity. SUMMARY OF THE INVENTION Among the objects of the present invention, therefore, is the provision of taxanes which compare favorably to taxol and docetaxel with respect to efficacy as anti-tumor agents and with respect to toxicity. In general, these taxanes possess a carbonate substituent at C-7, a hydroxy substituent at C-10, and a range of 0(2). 0(9), 0(14), and 0(13) side chain substituents. Briefly, therefore, the present invention is directed to the taxane composition, per se, to pharmaceutical compositions comprising the taxane and a pharmaceutically acceptable earner, and to methods of administration. Other objects and features of this invention wi(! be in part apparent and in part pointed out hereinafter. DETAILED DESORIPTION OF THE PREFERRED EMBODIMENTS In one embodiment of the present invention, the taxanes of the present invention correspond to structure (1): wherein R2 is acyloxy; R7 is carbonate; R9 is keto, hydroxy, or acyloxy; R10 is hydroxy; R,4 is hydrido or hydroxy; X3 is substituted or unsubstituted alky!, alkenyi, alkynyl, phenyl or heterocyclo, wherein alkyt comprises at least two carbon atoms; X5 is -COX10, -COOX10, or -CONHX10; X10 is hydrocarbyi, substituted hydrocarbyl, or heterocyclo; Ac is acetyl; and R7, R9, and R10 independently have the alpha or beta stereochemical configuration. (n one embodiment, R2 is an ester (R2aC(0)0-), a carbamate (R2jR2t,NC(0)0-), a carbonate (R2aOC(0)0-), or a thiocarbamate (R2aSC(0)0-) wherein R7a and R2 are independently hydrogen, hydrocarbyl, substituted hydrocarbyl or heterocydo. In a preferred embodiment, R2 is an ester CR23C(O)0-), wherein R7a is aryi or heteroaromatic. In another pretended embodiment, R^ 'S an ester (R2aC(0}0-}, wherein R2, is substituted or unsubstituted phenyl, furyl, thienyi, or pyridyl. In one particularly preferred embodiment, R2 is benzoyloxy. In one embodiment, R7 is RygOCOO-wherein R7A is (i) substituted or unsubstituted C1 to C8 alkyl {straight, branched or cyclic), such as methyl, ethyl, propyl, butyl, pentyl, or hexyl; (ii) substituted or unsubstituted C2 to C8 alkenyi (straight, branched or cyclic), such as ethenyl. propenyl, butenyl, pentenyl or hexenyi; (iii) substituted or unsubstituted C1 to C8 alkynyl (straight or branched) such as ethynyl, propynyi, butynyl, pentynyl, or hexynyl; (iv) substituted or unsubstituted phenyl; or (v) substituted or unsubstituted heterocydo such as furyl, thienyi, or pyridyl. The substrtuents may be hydrocarbyl or any of the heteroatom containing substituents identified elsewhere herein for substituted hydrocarbyl. In a preferred embodiment, R7a is methyl, ethyl, straight, branched or cyclic propyl, straight, branched or cyclic butyl, straight, branched or cyclic hexyi, straight or branched propenyl, isobutenyl, furyl or thienyi. In another embodiment, R7a is substituted ethyl, substituted propyl (straight, branched or cyclic), substituted propenyl (straight or branched), substituted isobutenyl, substituted furyl or substituted thienyi wherein the substituent(s) Is/are selected from the group consisting of heterocydo, aikoxy, alkenoxy, alkynoxy, aryloxy, hydroxy, proteded hydroxy, keto, acyloxy, nitro, amino, amido, thiol, ketal, acetal, ester and ether moieties, but not phosphorous containing moieties. While R9 is keto in one embodiment of the present invention, in other embodiments R9 may have the alpha or beta stereochemical configuration, preferably the beta stereochemical configuration, and may be, for example, a- or p-hydroxy or a- or Mcyloxy. For example, when R9 is acyloxy, it may be an ester (R9aC{0)0-), a carbamate (R9aR9bNC(0)0-), a carbonate (R9aOC(0)0-), or a thiocarbamate (R9BSC(0)0-) wherein R9, and R^ are independently hydrogen, hydrocarbyl, substituted hydrocartyl or heterocydo. if R9 is an ester {R9C(O)0-), R9a is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyi, substituted or unsubstituted aryl or substituted or unsubstituted hetenaaromatic. Still more preferably, R9 is an ester (R9aC(O)O-), wherein R9, is substituted or unsubstituted phenyl, substituted or unsubstituted furyl, substituted or, unsubstituted thienyi, or substituted or unsubstituted pyridyl. In one embodiment R5 is (R9aC(0P-) wherein R9^ is methyl, ethyl, propyl (slight, branched or cyclic), butyl (straight, branched or cydic), pentyl, (straight, branched or cyclic), or hexyl (straight, branched or cyclic). In another embodiment R9 is (R9aC(O)O-) wherein R9a is substituted methyl, substituted ethyl, substituted propyl (straight, branched or cyclic), substituted butyl (straight, branched or cyclic), substituted pentyl, (straight, branched or cyclic), or substituted hexyl (straight, branched or cyclic) wherein the substituent(s) is/are selected from the group consisting of heterocycio, aikoxy, alkenoxy, alkynoxy, aryioxy, hydroxy, protected hydroxy, keto, acyloxy, nrtPD, amino, amide, thiol, ketal, acetal, ester and ether moieties, but not phosphorous containing moieties. Exemplary X3 substituents include substituted or unsubstituted C; to C8 alkyl, substituted or unsubstituted Cj to C8 alkenyl, substituted or unsubstituted C; to Ca alkynyl, substituted or unsubstituted heteroaromatics rantaining 5 or 6 ring atoms, and substituted or unsubstituted phenyl. Exemplary prefen*ed X3 substituents include substituted or unsubstituted ethyl, propyl, butyl, cydopropyl, cydobutyl, cyclohexyl, isobutenyl, ftjjyl, thienyi, and pyridyl. . Exemplary X5 substituents include -COX^a, -COOX10 or -CONHXn, wherein X^o is substituted or unsutjstjtuted alkyl, alkenyl, phenyl or heteroaromatic. Exemplary preferred Xg substituents include -COXIQ, -COOX,a or -CONHX,o wherein X^Q is (I) substituted or unsubstituted C, to C8 alkyl such as substituted or unsubstituted methyl, ethyl, propyl (straight, branched or cyclic), butyl (straight, branched or cyclic), pentyl (straight, branched or cyclic), or hexyl (straight, branched or cyclic): (ii) substituted or unsubstituted Cj to C8 alkenyl such as substituted or unsubstituted ethenyl, propenyl (straight branched or cyclic), butenyl (straight, branched or cydic), pentenyl (straight, branched or cyclic) or hexenyl (straight, branched or cyclic); (iii) substituted or unsubstituted C3 to C8 alkynyl such as substituted or unsubstituted ethynyl, propynyl (straight or branched), butynyl (straight or branched), pentynyl (straight or branched), or hexynyl (straight or branched); (iv) substituted or unsubstituted phenyl, or (v) substituted or unsubstituted heteroaromatic such as furyl, thienyi, or pyridyl, wherein the substitijent(s) is/are selected from the group consisting of heterocycio, aikoxy, alkenoxy, alkynoxy, aryioxy, hydroxy, protected hydroxy, keto, acyloxy, nitro, amino, amido, thiol, ketal, acetal, ester and ether moieties, but not phosphonDus containing moieties, in one embodiment, the taxanes of tiie present invention con"espond to structure (2): wherein Rj is carbonate; Rio is hydroxy; X3 is substituted or unsubstituted alkyl, aikenyl, alkynyl, or heterocydo, wherein alky) comprises at least two carbon atoms; X5 is -COX,o. -COOX,(j, or -CONHX,^; and X10 is hydrocarbyi, substituted hydrocarbyl, or heterocydo. For example, in this preferred embodiment in which the taxane corresponds to structure (2), R^may be R2JOCQO- wherein R7a is substituted or unsubstituted metfiyi, ethyl, propyl, butyl, pentyf or hexyl, more preferably substituted or unsubstituted methyl, ethyl or propyl, still more preferably substituted or unsubstituted methyl, ethyl, and stii) more preferably unsubstituted methyl or ethyl. While R2^ is selected from among these, in one embodiment X3 is selected from substituted or unsubstituted alkyl, alkenyl, phenyl or heterocydo, more preferably substituted or unsubstituted alkenyl, phenyl or heterocydo, still more preferably substituted or unsubstituted phenyl or heterocydo, and still more preferably heterocydo such as furyl. thienyl or pyridyl. While R73 and X3 are selected from among these, in one embodiment X5 is selected from -COXio wherein X^^ is phenyl, alkyl or heterocydo, more preferably phenyl. Alternatively, while R^a and X3 are selected from among these, in one embodiment X5 is selected from -COX10 wherein X^, is phenyl, alkyl or heterocydo, more preferably phenyl, or Xg is -COOX10 wherein XIQ is alkyl, preferably t-butyl. Among the more preferred embodiments, therefore, are taxanes corresponding to structure 2 in which (i) X5 is -COOX^Q wherein X^, is tert-butyl or X5 is -COX10 wherein X10 is phenyl, (ii) X3 is substituted or unsubstituted cycioafkyl, aikeny!, phenyl or heterocycJo, more preferably substituted or unsubstituted isobutenyl, phenyl, furyl. tfiienyl, or pyridyt, still more preferably unsubstituted isobutenyl, furyl, thienyt or pyridyl, and (ili) R7a is unsubstituted methyl, ethyl or propyl, more preferably methyl or ethyl. Among the preferred embodiments, therefore, are taxanes corresponding to structure 1 or 2 wherein R^ is R7aOCOO- wherein R^, is methyl. In this embodiment, X3 is preferably cycloalkyi, isobutenyl, phenyl, substituted phenyl such as p-nitrophenyl, or heterocydo, more preferably heterocyclo, stiil more preferably Ivryl, thienyl or pyridyl; and X5 is preferably benzoyl, aikoxycarbonyl. or heterocyciocarbonyl, more preferably benzoyl, t-butoxycarbonyl or t-amyloxycarfaonyi. in one alternative of this embodiment, X3 is heterocycio; X5 is benzoyl, aikoxycarbonyl, or heterocyciocarbonyl, more preferably benzoyl, t-butoxycarbonyl or t-amyloxycarbonyl, still more preferably t-butoxycarbonyl; R, is benzoyl, R^ is keto and R^^ is hydrido. In another alternative of this embodiment, X3 is heterocyclo; X^ is benzoyl, alkoxycart:onyl. or heterocyciocarbonyl, more preferably benzoyl, t-butoxycarbonyl ort-amyloxycarbonyi, still more preferably t-butoxycarbonyl; R2 is benzoyl, R9 is keto and R„ is hydrido. In another alternative of this embodiment. X3 is heterocyclo; X5 is benzoyl, aikoxycarbonyl, or heterocyciocarbonyl, more preferably benzoyl, t-butoxycarbonyl ort-amyloxycarbonyl, still more preferably t-butoxycarbonyl; R2 Is benzoyl, R9 is keto and R14 is hydroxy. In another alternative of this embodiment, X3 is heterocyclo; Xj is benzoyl, alkoxycaribonyl, or heterocyciocarbonyl, more preferably benzoyl, t-butoxycarbonyl or t-amyloxycarbonyl, still more preferably t-butoxycarbonyl; R2 is benzoyl, R9 is hydroxy and R14 is hydroxy. In another alternative of this embodiment, X3 is heterocyclo; Xg Is benzoyl, aikoxycarbonyl, or heterocyciocarbonyl, more preferably benzoyl, t-butoxycarbonyl or t-amyloxycarbonyl, still more preferably t-butoxycarbonyi; R2 is benzoyl, R9 is hydroxy and R14 is hydrido. In another alternative of this embodiment, X3 is heterocydo; X5 is benzoyl, aikoxycarbonyl, or heterocyciocarbonyl, more preferably benzoyl, t-butoxycarbonyl ort-amyloxycarbonyi, still more preferably t-, butoxycarbonyt; R2 is benzoyl, R9 is acyloxy and R,^ is hydroxy. In another alternative of this embodiment, X3 is heterocyclo; X5 is benzoyl, aikoxycarbonyl, or heterocydocarbonyl, more preferably benzoyl, t-butoxycarbonyl or t-amyloxycarbonyl, stil! more preferably t-butoxycarbonyi; R2 is benzoyl, R9 is acyJoxy and R^^ Is hydrido. \n each of the alternatives of this embodiment when the taxane has structure 1, R2 and Rio may each have the beta stereochemical configuration, R7 and R10 may each have the alpha stereochemical configuration. Hy may have the alpha stereochemical configuration while R^o has the beta stereochemicai configuration or R7 may have the beta stereochemical configuration while R^^ has the alpha stereochemical configuration. Also among the preferred embodiments are taxanes corresponding to structure 1 or 2 wherein R2 is R7aOCOO- wherein R^, is ethyl. In this embodiment, X3 is preferably cydoaikyl, isobutenyl, phenyl, substituted phenyl such as p-nitrophenyl, or heterocycio, more preferably heterocycio, still more preferably furyl, thieny! or pyridyl; and X5 is preferably benzoyl, alkoxycarbonyl, or heterocydocarbonyi, more preferably benzoyl, t-butoxycarbonyl ort-amyloxycarbonyi. In one alternative of this embodiment, X3 is heterocycio; X5 is benzoyl, alkoxycarbonyl, or heterocydocarbonyi, more preferably benzoyl, t-butoxycarbcn yl or t-amyioxycart}ony[, still more preferably t-butoxycarfaony[; R^ is benzoyl, R9 Is keto and Ri^ is hydrido. In another altemative of this embodiment, X3 is heterocycio; X5 is benzoyl, alkoxycarbonyl, or heterocydocarbonyi, more preferably benzoyl, t-butoxycarfaonyl ort-amyloxycarbonyl, still more preferably t-butoxycartsonyi; R^ is benzoyl, R9 is keto and R,4 is hydrido. In another altemative of this embodiment, X3 is heterocydo; Xj Is benzoyl, alkoxycarbonyl, or heterocydocarbonyi, more preferably benzoyl, t-butoxycarbonyl ort-amyloxycarbonyl, still more preferably t-butoxycarbonyl; R2 is benzoyl, R9 is keto and Ri4 Is hydroxy. In another altemative of this embodiment, Xj is heterocycio; X5 is benzoyl, alkoxycarbonyl, or heterocydocarbonyi, more preferably benzoyl, t-butoxycarbonyl or t-amyioxycarbonyl, still more preferably t-butoxycarbonyl; R2 Is benzoyl, R9 is hydroxy and R14 is hydroxy. In another altemative of this embodiment, X3 is heterocydo; X5 is benzoyl, alkoxycartjonyl, or heterocydocarbonyi, more preferably benzoyl, t-butoxycarbonyl ort-amyloxycarbonyl, still more preferably t-butoxycarbonyl; R2 is benzoyl. R9 is hydroxy and R^^ is hydrido. in another altemative of this embodiment, X3 is heterocydo; X5 Is benzoyl, alkoxycarbonyl, or heterocydocarbonyi, more preferably benzoyl, t-butoxycarbonyl or t-amyloxycarbonyl, still more preferably t-butoxycarbonyl; R; is benzoyl, R9 is acyloxy and R,4 is hydroxy. In another alternative of this embodiment, X3 ts heterocydo; X5 is benzoyl, alkoxycarbonyl, or heterocydocarbonyi, more preferably benzoyl, t-butoxycarbonyl ort-amyloxycarbonyl, still more preferably t-butoxycarbony!; R; is benzoyl, R9 is acyloxy and R,4 is hydrido. In each of the alternatives of this embodiment when the taxane has structure 1, R7 and Rig may each have the beta stereochemical configuration, R^ and Ru, may each have the alpha stereochemical configuration, Rj may have the alpha stereochemical configuration while R^j has the beta stereochemical configuration or R7 may have the beta stereochemical configuration while R7a has the alpha stereochemical configuration. Also among the preferred embodiments are taxanes conresponding to structure 1 or 2 wherein R? is RTaOCOO- wherein R^^ is propyl. In this embodiment, X3 is preferably cycloalkyl, isobutenyl, phenyl, substituted phenyl such as p-nitrophenyl, or heterocycio, more preferably heterocycio, still more preferably furyl, thienyl or pyridyl; and Xg is preferably benzoyl, alkoxycarbonyl, or heterocyciocarbonyl, more preferably benzoyl, t-butoxycarbonyl ort-amyioxycarbonyl. In one alternative of this embodiment, X3 is heterocycio; X5 is benzoyl, alkoxycarbonyl, or heterocyciocarbonyl, more preferably benzoyl, t-butoxycarbonyi ort-amyloxycarbonyl, still more preferably t-butoxycarbonyl; R, is benzoyl, R9 Is keto and R^^ 'S hydrido. In another alternative of this embodiment, X3 is heterocycio; X^ is benzoyi, alkoxycarbonyl, or heterocyciocarbonyl, more preferably benzoyl, t-butoxycarbonyl or t-amyloxycarbonyl, still more preferably t-butoxycarbonyl; R2 is benzoyl, R9 is keto and R^^ is hydrido. In another alternative of this embodiment, X3 is hetenDcycIo; X5 is benzoyl, alkoxycarbonyl, or heterocyciocarbonyl, more preferably benzoyi, t-butoxycarbonyl or t-amyloxycarbonyl, still more preferably t-butoxycarbonyl; R2 is benzoyl, R9 Is keto and Ri4 is hydroxy. In another aitemative of this embodiment, X3 is heterocycio; X5 is benzoyl, alkoxycarbonyl, or heterocyciocarbonyl, more preferably benzoyl, t-butoxycarbonyl or t-amyloxycarbonyl, still more preferably t-butoxycarbonyl; R2 is benzoyl, R9 is hydroxy and Ru is hydroxy. In another aitemative of this embodiment, X3 is heterocycio; Xg is benzoyl, alkoxycarbonyl, or heterocyciocarbonyl, more preferably benzoyl, t-butoxycarbonyl or t-amyloxycariDonyi, still more preferably t-butoxycarbonyl; R^ is benzoyl, R9 is hydroxy and R14 is hydrido. In another aitemative of this embodiment, X3 is heterocycio; X5 is benzoyl, alkoxycarbonyl, or heterocyciocarbonyl, more preferably benzoyi, t-butoxycarbonyl or t-amyloxycarbonyl, still more preferably t-butoxycarbonyl; R2 is benzoyl, R9 is acyloxy and R^^ is hydroxy. In another aitemative of this embodiment. X3 is heterocycio; Xj is benzoyl, alkoxycartaonyi. or heterocyciocarbonyl, more preferably benzoyl, t-butoxycarbonyi or t-amyloxycarbonyl, still more preferably t-butoxycarbonyl; R2 is benzoyl, R9 is acyloxy and R,4 is hydrido. In each of the alternatives of this embodiment when the taxane has structure 1, R7 and Rio may each have the beta stereochemical configuration, R7 and Rm may each have the alpha stereochemical configuration. Rj may have the alpha stereochemical configuration while R10 has the beta stereochemical configuration or R7 may have the beta stereochemical configuration while Rio has the alpha stereochemical configuration. Taxanes having the genera) fonmula 1 may be obtained by treatment of a p-lactam with an aikoxide having the taxane tetracyclic nucleus and a C-13 metallic oxide substituent to form compounds having a ^-amido ester substituent at C-13 (as described more fully in Holton U.S. Patent 5,466,834), followed by removal of the hydroxy protecting groups. The P-lactam has the following structural formula {3); wherein Pg is a hydroxy protecting group and Xj and X5 arenas previously defined and the aikoxide has the staictural formula (4): wherein M is a metal or ammonium, P^Q is a hydroxy prcitecting group and R2, R^, R7 and Ri4 are as previously defined. Aikoxide 4 may be prepared from 10-deacetylbaccatin III (or a derivative thereof) by selective protection of the C-10 hydroxyl group and then acylation of the C-7 hydroxy! group followed by treatment with a metallic amide. In one embodiment of the present invention, the C(10) hydroxyl group of 10-deacetylbaccatin III is selectively protected with a silyl group using, for example, a silylamide or bissilyamlde as a siiylating agent. Prefen"ed silylating agents include tri(hydrocarbyl)silyl-trifiuoromethylacetamides and bis tri(hydrocarbyl> sily!trtfiuorDmethyiacetamides (with the hydracarijyl moiety being substituted or unsubstituted alky( or aryt) such as N,0-bis-(trimethyisiiy[) trifluoroacetamide, N,0-bis-{triethylsily!)trifiuoroacetamide, N-methyl-N-triethyisiiyltrifluoroacetamide, and N,0-bis(t-butyldimethylsilyl)tnf)uoroacetamide. The sifylating agents may be used either aione or in combination with a catalytic amount of a base such as an alkali metal base. Alkali metal amides, such as lithium amide'catalysts, in general, and lithium hexamethyldisiiazide, in particular, are preferred. The solvent for the selective silylation reaction is preferably an ethereal solvent such as tetrahydrofuran. Alternatively, however, other solvents such as ether or dimettioxyethane may be used. The temperature at which the C(10) selective silylation is carried out is not narrowly critical. In general, however, it is canied out at 0 X or greater. Selective acylation of the C(7) hydroxyl group of a C(10) protected taxane to form a C(7) carbonate can be achieved using any of a variety of common acylating agents such as a haioformates. In general, acylation of the C(7) hydroxy group of a C(10) protected taxane are more efficient and more selective than are C(7) acylations of a 7,10-dihydroxy taxane such as 10-DAB; stated another way, once the C(10) hydroxy! group has been protected, there is a significant difference in the reactivity of the remaining C(7), C(13), and C(1) hydroxy! groups. These acylation reactions may optionally be carried out in the presence or absence of an amine base. Derivatives of 10-deacetylbaccatin III having alternative substituents at C(2), C{9) and C{14) and processes for their preparation are known in the art. Taxane derivatives having acyloxy substituents other than benzoyloxy at C(2) may be prepared, for example, as described in Hoiton et al., U.S. Patent No. 5,728,725 or Kingston et al., U.S. Patent No. 6,002,023. Taxanes having acyloxy or hydroxy substituents at C(9) in place of keto may be prepared, for example as described in Hotton et a)., U.S. Patent No. 6,011,056 or Gunawandana et al., U.S. Patent No. 5,352,806. Taxanes having a beta hydroxy substituent at C(14) may 30 be prepared from naturally occuning 14-hydroxy-10-deac6tyibaccatln 111. Processes for the preparation and resolution of the (3-lactam starting material are generally well known. For example, the (3-lactam may be prepared as described in Holton, U.S. Patent No. 5,430,160 and tiie resulting enatiomeric mixtures of p-lactams may be resolved by a stereoselective hydrolysis using a lipase or enzyme as described, for example, in Patel, U.S. Patent No. 5,879,929 Patel U.S. Patent No. 5,567,614 or a liver homogenate as described, for example. in PCT Patent Application No. 00/41204. In a prefen-ed embodiment in which the p-]actam is ftjryl substituted at the C(4) position, the p-lactam can be prepared as illustrated In the following reaction scheme: wherein Ac is acetyl, NEtj is triethyiamine, CAN is eerie ammonium nitrate, and p-TsOH is p-toluenesulfonic acid. The beef liver resolution may be carried out, for example, by combining the enatiomeric P-lactam mixture with a beef liver suspension (prepared, for example, by adding 20 g of frozen beef liver to a blender and then adding a pH 8 buffer to make a total volume of 1 L). Compounds of formula 1 of the instant invention are useful for inhibiting tumor growth in mammals tnciuding humans and are preferably administered in the form of a pharmaceutical composition comprising an effective antitumor amount of a compound of the instant invention in combination with at least one pharmaceutically or pharmacologically acceptable carrier. The carrier, also known in the art as an excipient. vehicle, auxiliary, adjuvant, or diluent, is any substance which is pharmaceuticaily inert, confers a suitable consistency or form to the composition, and does not diminish the therapeutic efficacy of the antitumor compounds. The carrier is "phamiaceuticaily or pharmacologically acceptable" if it does not produce an adverse, alleR9ic or other untoward reaction when administered to a mammal or human, as appropriate. The phannaceutical compositions containing the antitumor compounds of the present invention may be fonnulated in any conventional manner. Proper fomiulation is dependent upon the route of administration chosen. The compositions of the invention can be fonnulated for any route of administration so long as the taR9et tissue is available via that route. Suitable routes of administration include, but are not limited to, oral, parenteral (e.g., intravenous, intraarterial, subcutaneous, rectal, subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intraperitoneal, or intrastemai), topical (nasal, transdermal, intraocular), intravesical, intrathecal, enteral, pulmonary, intraiymphatic, intracavitai, vaginal, transurethral, Intradermal, aural, intramammary, buccal, orthotopic, intratracheal, intralesional, percutaneous, endoscopical, transmucosal, sublingual and intestinal administration. Pharmaceuticaily acceptable carriers for use in the compositions of the present invention are well known to those of ordinary skill in the art and are selected based upon a number of factors: the particular antitumor compound used, and its concentration, stability and intended bioavailability; the disease, disorder or condit'on being treated with the composition; the subject, its age, size and general condition; and the route of administration. Suitable carriers are readily detemined by one of ordinary skill in the art (see, for example, J. G. Nairn, in: Reminoton's Pharmaceutical Science (A, Gennaro, ed.). Mack Publishing Co., Easton. Pa., (1985), pp. 1492-1517, the contents of which are incorporated herein by reference). The compositions are preferably formulated as tablets, dispersible powders, pills, capsules, gelcaps, caplets, gels, liposomes, granules, solutions, suspensions, emulsions, syrups, elixirs, troches, dragees, lozenges, or any other dosage form which can be administered orally. Techniques and compositions for making oral dosage forms useful in the present invention are described in the foHowing references; 7 Modem Pharmaceutics. Chapters 9 and 10 (Bankers Rhodes, Editors, 1979); Lieberman et al., Pharmaceutical Dosaoe Forms: Tablets (1981); and Ansel, Introduction to Phamiaceutical DQsaoe Forms 2nd Edition (1976). The compositions of the invention for oral administration comprise an effective antitumor amount of a compound of the invention in a phamiaceuticaily acceptable earner. Suitable carriers for solid dosage forms include sugars, starches, and other conventional substances including lactose, talc, sucrose, gelatin, carboxymethylcsllulose, agar, mannitol, sorbitol, calcium phosphate, calcium carbonatQ, sodium carixjnate, kaolin, alginic acid, acacia, com starch, potato starch, sodium saccharin, magnesium carbonate, tragacanth, microcrystalline cellulose, coiloidai silicon dioxide, croscarmellose sodium, l3lc, magnesium stearate, and stearic acid. Further, such solid dosage forms may be uncoated or may be coated by known techniques; e.g., to delay disintegration and absorption. The antitumor compounds of the present invention are also preferably fbrmuiated for parenteral administration, e.g., formulated for injection via intravenous, intraarterial, subcutaneous, rectal, subcutaneous, intramuscular, intraortiital, intracapsular, intraspinal, intraperitoneal, or Intrastemal routes. The compositions of the invention for parenteral administration comprise an effective antitumor amount of the antitumor compound in a pharmaceutically acceptable earner. Dosage forms suitable for parenteral administration include solutions, suspensions, dispersions, emulsions or any other dosage fomi which can be administered parenterally. Techniques and compositions for making parenteral dosage forms are known in the art. Suitable earners used in formulating liquid dosage forms for oral or parenteral administration include nonaqueous, pharmaceuticatly-acceptable polar solvents such as oils, alcohols, amides, esters, ethers, ketones, hydrocarbons and mbctures thereof, as well as water, saline solutions, dextrose solutions (e.g., DW5), electrolyte solutions, or any other aqueous, pharmaceutically acceptable liquid. Suitable nonaqueous, pharmaceutically-acceptable polar solvents Include, but are not limited to, alcohols (e.g., a-glycerol formal, 3-glycerol formal, 1, 3-butyieneglycol, aliphatic or aromatic alcohols having 2-30 carbon atoms such as methanol, ethanol, propanol, isopropanol, butanol, t-butanol, hexanol, octanol, amylene hydrate, benzyl alcohol, glycerin (glycerol), glycol, hexylene glycol, tetrahydrofurfuryl alcohol, lauryl alcohol, cetyl alcohol, or stearyl alcohol, fatty acid esters of fatty alcohols such as polyalkylene glycols (e.g., polypropylene glycol, polyethylene glycol), sorbitan, sucrose and cholesterol); amides (e.g., dimethylacetamide (DMA), benzyl benzoate DMA, dimethylfonnamlde, N-([5- hydraxyethyl)-lactamide, N, N-dimeth>^acetamide.amrdes. 2-pyrroIidinone, l-methyl-2-pyrroiidinDne, or polyvinylpyrrolidone); esters (e.g., 1-methyl-2-pyiTolidinone, 2-pyrrolidinone, acetate esters such as monoacetin, diacetin, and triacetin. aliphatic or aromatic esters such as ethyl caprylate or Qctanoate, alkyl oleate, benzyl benzoate, benzyl acetate, dimethyisu If oxide (DMSO). esters of glycerin such as mono, di, ortri-glyceryl citrates or tartrates, ethyl benzoate. ethyl acetate, ethyl carbonate, ethyl lactate, ethyl oleate, fatty acid esters of sorbitan, fatty acid derived PEG esters, glyceryl monostearate, glyceri^ie esters such as mono, di, ortri-giycerides, fatty acid esters such as isopropyl myristrate, fatty acid derived PEG esters such as PEG-hydroxyoleate and PEG-hydroxystearate, N-methyl pyrrolidinone. pluronic 60, polyojcyethylene sorbitol oleic polyesters such as poly(ethoxylated)3(^^o sorbitol poly(oleate)2j poly(oxyethylene)i5.2o nnonooleate, poly(oxyethylene)i5.2o mono 12-hydroxystearate, and poIy(oxyethy!ene)i5.2Q mono ricinoleate, polyoxyethylene sorbitan esters such as polyoxyethylene-sorbitan monooleate, poiyoxyethylene-sorbitan monopaimitate, poiyoxyethylene-sorbitan monolaurate, poiyoxyethylene-sorbitan monostearate, and Polysorbate® 20,40, 60 or 80 from ICI Americas, Wilmington, DE, polyvinylpyrrolidone, alkyleneoxy modified fatty acid esters such as polyoxyl 40 hydrogenated castor oil and polyoxyethylated castor oils (e.g., Cremophor® EL solution or Cremophor® RH 40 solution), saccharide fatty acid esters (i.e., the condensation product of a monosaccharide (e.g., pentoses such as ribose, ribulose, arabinose, xylose, lyxose and xylulose, hexoses such as glucose, fnjctose, galactose, mannose and sorbose, trioses, tetroses, heptoses, and octoses), disaccharide (e.g., sucrose, maltose, lactose and trehalose) or oligosaccharide or mixture thereof with a C1-C22 fatty acid(s)(e.g., saturated fatty acids such as caprylic acid, capric acid, lauric acfd, myristic acid, palmitic acid and stearic acid, and unsaturated fatty acids such as paimitoleic acid, oleic acid, elaidic acid, erucic acid and linoieic acid)), or steroidal esters); alkyl, aryl, or cyclic ethers having 2-30 carbon atoms (e.g., diethyl ether, tetrahydrofuran, dimethyl isosorbide, diethylene glycol monoethyl ether); glycofurol (tetrahydrofurfuryl alcohol polyethylene glycol ether); ketones having 3-30 carbon atoms (e.g., acetone, methyl ethyl ketone, methyl isobutyl ketone); aliphatic, cycloaliphatic or aromatic hydnscarbons having 4-30 carbon atoms (e.g., benzene, cyclohexane, dichloromethane, dioxolanes, hexane, n-decane. n-dodecane, n-hexane, sulfolane, tetramethylenesulfon, tetramethylenesulfoxide, toluene, dimethyisu If oxide (DMSO), or tetramethylenesulfoxide); oils of mineral, vegetable, animal, essential or synthetic origin (e.g., mineral oils such as aliphatic or wax-based hydrocarbons, aromatic hydrocarbons, mixed aliphatic and aromatic based hydrocarbons, and refined paraffin oil, vegetable oils such as iinseed, tung, saffiower, soybean, castor, cottonseed, groundnut, rapeseed, coconat, palm, olive, com, com germ, sesame, persic and peanut oil and glycerides such as mono-, di- or triglycerides, animal oils such as fish, marine, sperm, cod-liver, haliver, squalene. squalane, and shark liver oil, oleic oils, and polyoxyethylated castor oil); alkyl or aryt halides having 1-30 carbon atoms and optionally more than one halogen substituent; methylene chloride; monoethanolamine; petroleum benzin; trolamine; omega-3 polyunsaturated fatty acids (e.g., alpha-llnolenic acid, eicosapentaenoic acid, docosapentaenoic acid, or docosahexaenoic acid); polyglycol ester of 12-hydroxystearic 3cJd and polyethylene glycol (Solutol® HS-15, from BASF, Ludwigshafen, Germany); polyoxyethylene glycerol; sodium laurate; sodium oleate; or sorbitan monooleate. Other pharmaceutically acceptable solvents for use in the invention are well known to those of ordinary skill in the art, and are identified In The Chemotherapy Source Book (Williams & Wiikens Publishing), The Handbook of Pharmaceutical Exciplents. (American Pharmaceutical Association, Washington, D.C., and The Pharmaceutical Society of Great Britain, London, England, 1968), Modem Phanmaceutics. (G. Banker et ai., eds.. 3d ed.)(Marcel Dekker, Inc., New York. New York, 1995), The Pharmacoloaicat Basis of Theraoeutics. (Goodman & Giiman, MC8raw Hill Publishing), Pharmaceutical Dosage Formg. (H. Liebennan et al., eds., )(Marcel Dekker, Inc., New York, New York, 1980), Remington's Pharmaceutical Sciences (A. Gennaro, ed., 19tti ed.)(Mack Publishing, Easton, PA. 1995), The United States PhannacoDeia 24. The National FormuJarv 19, (National Publishing, Philadelphia, PA, 2000), A.J. Spiegel et al., and Use of Nonaqueous Solvents in Parenteral Products, JOURNAL OF PHARMACEUTICAL SCIENCES, Vol. 52, No. 10, pp. 917-927 (1963). Prefen-ed solvents include those known to stabilize the antitumor compounds, such as oils rich in triglycerides, for example, saffiower oil, soybean oil or mixtures thereof, and alkyieneoxy modified fetty acid esters such as polyoxyl 40 hydrogenated casior oft and polyoxyethylated castor oils (e.g., Cremophor® EL solution or Cremophor® RH 40 solution). Commercially available triglycerides include Intralipid® emulsified soybean oil (Kabi-Pharmacia Inc., Stockholm, Sweden), Nutraiipid ® emulsion (MC8aw, Irvine, Califomia), LIposyn® II 20% emulsion (a 20% fat emulsion solution containing 100 mg safflower oil, 100 mg soybean oil, 12 mg egg phosphatides, and 25 mg glycerin per ml of solution; Abbott Laboratories, Chicago, Illinois), Liposyn® 111 2% emulsion {a 2% fat emulsion solution containing 100 mg safflower oil, 100 mg soybean oil, 12 mg egg phosphatides, and 25 mg glycerin per ml of solution; Abbott Laboratories, Chicago, Illinois), natural or synthetic glycerol derivatives containing the docosahexaenoyl group at ieveis between 25% and 100% fay weight based on the total fatty acid content (Dhasco® (from Martek Biosciences Corp., Columbia, MD), DHA Maguro® (from Darto Enterprises, Los Angeles, CA), Soyacal®, and Travemulsion®. Ethanol is a preferred solvent for use In dissolving the antitumor compound to form solutions, emulsions, and the like. Additional minor components can be included in the compositions of the invention for a variety of purposes well known in the pharmaceutical industry. These components will for the most part impart properties which enhance retention of the antitumor compound at the site of administration, protect the stability of the composition, control the pH, facilitate processing of the antitumor compound into pharmaceutical formulations, and the like. Preferably, each of these components Is individually present in less than about 15 weight % of the total composition, more preferabfy less than about 5 weight %, and most preferably less than about 0.5 weight % of the total composition. Some components, such as fiiJers or diluents, can constitute up to 90 wt.% of the total composition, as is well known in the formulation art. Such additives Indude cryoprotective agents for preventing reprecipitation of the taxane, surface active, wetting or emulsifying agents (e.g., lecithin, polysorbate-80, Tween® 80, pluronic 60, polyoxyethylene stearate ), preservatives (e.g., ethyl-p-hydroxybenzoate). micnabial preservatives {e.g., benzyl alcohol, phenol, m-cresol, chiorobutanol, sorbic acid, thimenasal and paraben), agents for adjusting pH or buffering agents (e.g., acids, bases, sodium acetate, sorbrtan monolaurate), agents for adjusting osmolarity (e.g., glycerin), ttiickeners (e.g., aluminum monostearate, stearic acid, cetyl alcohol, stearyl alcohol, guar gum, methyl cellulose, hydroxypropylcellulose, tristearin, cetyi wax esters, polyethylene glycol), colorants, dyes, flow aids, non-volatiie silicones (e.g., cyciomethicone), days (e.g., bentonftes), adhesives, bulking agents, flavorings, sweeteners, adsorbents, fillers (e.g., sugars such as lactose, sucrose, mannitol, or sorbitol, cellulose, or calcium phosphate), diluents {e.g., water, saline, electrolyte solutions), binders (e.g., starches such as maize starch, wheat starch, rice starch, or potato starch, gelatin, gum tragacanth, methyl cellulose, hydroxypropyl methylcellulose, sodium carisoxymethyl cellulose, poiyvinyipyrrolidone, sugars, polymers, acacia), disintegrating agents (e.g., starches such as maize starch, wheat starch, rice starch, potato starch, or carboxymethyl starch, cross-linked polyvinyl pyrrolidone, agar, atginic acid or a salt thereof such as sodium alginate, croscarmellose sodium or crospovidone), lubricants (e.g., silica, talc, stearic acid or salts thereof such as magnesium stearate, or polyethylene glycol), coating agents (e.g., concentrated sugar solutions including gum arabic, talc, polyvinyl pyrrolidone, cartiopol gel, polyethylene glycol, or titanium dioxide), and antioxidants (e.g., sodium metabisulfrte, sodium bisulfite, sodium sulfite, dextrose, phenols, and thiophenols). In a preferred embodiment, a pharmaceutical composition of the invention comprises at least one nonaqueous, pharmaceuticaily acceptable solvent and an antitumor compound having a solubility in ethanol of at least about 100, 200. 300, 400, 500, 600, 700 or 800 mgyml. WhiJe not being bound to a particular theory, it is believed that the ethanol solubility of the antitumor compound may be directly related to its efficacy. The antitumor compound can also be capable of being crystallized from a solution. In other words, a crystalline antftumor compound, such as compound 1393, can be dissolved in a solvent to form a solution and then recrystallized upon evaporation of the solvent without the formation of any amorphous antitumor compound. It is also preferred that the antitumor compound have an ID50 value (l.e, the drug concentration producing 50% inhibition of colony formation) of at least 4, 5, 6, 7, 8, 9, or 10 times less that of paclitaxel when measured according to the protocol set forth in the working examples. Dosage fomi administration by ttiese routes may be continuous or intemiittent, depending, for example, upon the patient's physiological condition, whether the purpose of the administi-ation is therapeutic or prciphyiactic, and otiier factors known to and assessable by a skilled practitioner. Dosage and regimens for the administration of the pharmaceutical compositions of the invention can be readily detemnined by those with ordinary , skill in treating cancer. It is understood that the dosage of the antitijmor compounds will be dependent upon tiie age, sex, health, and weight of the recipient, kind of concun-ent treatment, if any, frequency of treatment, and the nature of the effect desired. For any mode of administration, the actual amount of antitumor compound delivered, as well as the dosing schedule necessary to achieve the advantageous effects described herein, will also depend, in part, on such factors as the bioavailability of the antitumor compqund, the disgnder being tt^ated, the desired therapeutic dose, and other factors that will be apparent to those of skill in the art. The dose administered to an animal, particuiariy a human, in the rontext of the present invention should be sufficient to effect the desired therapeutic response in the animal over a reasonable period of time. Preferably, an effective amount of Vne antitumor compound, whether administered orally or by another route, is any amount which would result in a desired therapeutic response when administered by that route. Preferably, the compositions for oral administration are prepared in such a way that a single dose in one or more oral preparations contains at least 20 mg of the antitumor compound per m^ of patient body surface area, or at least 50, 100, 150, 200, 300, 400, or 500 mg of the antitumor compound per m^ of patient body surface area, wherein the average body surface area for a human is 1.8 ml Preferably, a single dose of a composition for oral^administration contains from atiout 20 to about 500 mgofthe antitumor compound per m^ of patient body surface area, more preferably from about 25 to about 400 mg/m^' even more preferably, from about 40 to about 300 mg/m^, and even more preferably from about 50 to about 200 mg/m^. Preferably, the compositions for parenteral administration are prepared, in such a way that a single dose contains at least 20 mg of the antitumor compound per m^ of patient body surface area, or at least 40, 50, 100,150, 200, 300, 400, or 500 mg of the antitumor compound per m^ of patient body surface area. Preferably, a single dose in one or more parenteral preparations contains from about 20 to about 500 mg of the antitumor compound per m^ of patient body surface area, more preferably from about 40 to about 400 mg/m^' and even more preferably, fn^m about 60 to about 350 mg/m^. However, the dosage may vary depending on the dosing schedule which can be adjusted as necessary to achieve the desired therapeutic effect. It should be noted that the ranges of effective doses provided herein are not intended to limit the invention and represent preferred dose ranges. The most preferred dosage will be tailored to ^e individual subject, as is understood and determinable by one of ordinary skill in the art without undue experimentation. The concentration of the antitumor compound in a liquid pharmaceutical composition is preferably between about 0.01 mg and about 10 mg per ml of the ojmposition, rrwre preferably between about 0.1 mg and about 7 mg per m), even more preferably between about 0.5 mg and about 5 mg per ml, and most preferably between about 1.5 mg and about 4 mg per ml. Relatively low concentrations are generally prefen'ed because the antitumor compound is most soluble in the solution at low concentrations. The concentration of the antitumor compound in a solid phamiaceutical composition for oral administration is preferably between about 5 weight % and about 50 weight %, based on the total weight of the composition, more preferably between about 8 weight % and about 40 weight %, and most preferably between about 10 weight % and about 30 weight %. In one embodiment, solutions for oral administration are prepared by dissolving an antitumor compound in any pharmaceutically acceptable solvent capable of dissolving Uie compound (e.g., ethanol or methylene chloride) to form a solution. An appropriate volume of a carrier which is a solution, such as Cremophor® EL solution, is added to the solution while stining to form a pharmaceutically acceptable solution for oral administration to a patient. If desired, such solutions can be formulated to contain a minimal amount of, or to be free of, ethanol, which is known \n the art to cause adverse physblogical effects when administered at certain concentrations in oral formulations. In another embodiment, powders or tablets for oral administration are prepared by dissolving an antitumor compound in any pharfnaceutically acceptable solvent capable of dissolving the compound (e.g.,ethanol or methylene chloride) to fonn a solution. The solvent can optionally be capable of evaporating when the solution is dried under vacuum. An additional carrier can be added to the solution prior to drying, such as Cremophor® EL solution. The resulting solution Is dried under vacuum to form a glass. The glass is then mixed with a binder to fonn a powder. The powder can be mixed with fillers or other conventional tabletting agents and processed to form a tablet for ota\ administration to a patient The powder can also be added to any liquid canier as described above to form a solution, emulsion, suspension or the like for oral administration. Emulsions for parenteral administration can be prepared by dissolving an antitumor compound in any pharmaceutically acceptable solvent capable of dissolving the compound (e.g., ethanol or methylene chloride) to form a solution. An appropriate volume of a carrier which is an emulsion, such as Liposyn® II or Liposyn® 111 emulsion, is added to the solution while stirring to fonn a pharmaceutically acceptable emulsion for parenteral administration to a patient If desired, such emulsions can be formulated to a>ntain a minimal amount of, or to be free of, ethanol or Cremophoi® snlution. which are known in the art to cause adverse physiological effects when administered at certain concentrations in parenteral formulations. Solutions for parenteral administration can be prepared by dissolving an antitumor compound in any phamiaceutically acceptable solvent capable of dissolving the compound (e.g., ethanol or methylene chlorideXto form a solution. An appropriate volume of a carrier which is a solution, such as Cremophor® solution, is added to the solution while stin^ng to form a phamiaceutically acceptable solution for parenteral administration to a patient. If desired, such solutions can be fomiulated to contain a minimal amount of, or to be free of, ethanol or Cremophor® solution, which are known in the art to cause adverse physiological effects when administered at certain concentrations in parenteral fonnulations. If desired, the emulsions or solutions described above for orat or parenteral administration can be packaged in IV bags, viaJs or other conventional containers in concentrated forni and diluted with any phamiaceutically acceptable liquid, such as saline, to fonri an acceptable taxane concentration prior to use as is known in the art. Definitions The terms "hydnscarbon" and "hydrocarbyl" as used herein describe oR9anic compounds or radicals consisting exclusively of the elements carbon and hydrogen. These moieties include alkyl, alkenyl, alkynyl, and aryl moieties. These moieties also Include alkyl, alkenyl, alkynyl. and aryi moieties substituted with other aliphatic or cyclic hydnacarbon groups, such as alkaryl, alkenaryl and alkynaryf. Unless othenvise indicated, these moieties preferably comprise 1 to 20 carbon atoms. The "substitijted hydrocarbyl" moieties described herein are hydrocarbyl moieties which are substituted with at least one atom other than carbon, including moieties in which a carbon chain atom is substituted writh a hetero atom such as nitrogen, oxygen, silicon, phosphorous, boron, sulfur, or a halogen atom. These substttuents include halogen, heterocyclo, alkoxy, alkenoxy, alkynoxy, aryloxy, hydra)fy, protected hydroxy, keto, acy\, acyloxy, nitro, amino, amkio, nftro, cyano, thiol, ketals, acetals, esters and ethers. Unless otherwise indicated, the alkyl groups described herein are preferably lower alkyl containing from one to eight carbon atoms in the principal chain and up to 20 carbon atoms. They may be straight or branched chain or cyclic and include methyl, ethyl, propyl, isopropyl, butyl, hexyl and the like. Unless otherwise indicated, the alkenyt groups described herein are preferably lower alkenyl cx>ntaining from two to eight carbon atoms in the principal chain and up to 20 carbon atoms. They may be straight or branched chain or cyclic and include ethenyl, propenyl, isopropeni^. butenyl. isobutenyl, hexenyl, and the like. Unless othenwise indicated, the aikynyl groups described herein are preferably lower aikynyl containing from two to eight cartmn atoms in the principal chain and up to 20 carbon atoms. They may be straight or branched chain and indude ethynyi, propynyi, butynyl, isobutynyl, hexynyl, and the like. The terms "aryl" or "ar" as used herein alone or as part of another group denote optionally substituted homocyclic aromatic groups, preferably monocyclic or bicyclic groups OTntaining from 6 to 12 cartons in the ring portion, such as phenyl, biphenyJ, naphthyi, substituted phenyl, substituted biphenyl or substituted naphthyl. Phenyl and substituted phenyl are ttie more preferred aryl. The terms "halogen" or "halo" as used herein alone or as part of another group refer to chlorine, bromine, fluorine, and iodine. The tenns "heterocyclo" or "heterocyclic" as used herein alone or as part of another group denote optionally substituted, fully saturated or unsaturated, monocyclic or bicyclic, aromatic or nonaromatic groups having at least one hetenaatom in at least one ring, and preferably 5 or 6 atoms in each ring. The heterocydo group preferably has 1 or 2 oxygen atoms, 1 or 2 sulfur atoms, and/or 1 to 4 nitrogen atoms in the ring, and may be bonded to the remainder of the molecule through a cartion or heteroatom. Exemplary heterocyclo include heteroaromatics such as furyl, thienyl, pyridyl, oxazolyl, pyrrolyl, indolyl, quinolinyl, or isoquinolinyl and the like. Exemplary substituents include one or more of the following groups: hydrocarbyl, substituted hydrocarbyl, keto, hydroxy, protected hydroxy, acyt, acyloxy, alkoxy, alkenoxy, alkynoxy, aryloxy, halogen, amido, amino, nitro, cyano, thiol, ketals, acetals, esters and ethers. The term "heteroaramatic" as used herein alone or as part of another group denote optionally substituted aromatic groups having at least one heteroatom in at least one ring, and preferably 5 or 6 atoms in each ring. The heteroaromatic group preferably has 1 or 2 oxygen atoms, 1 or 2 sulfur atoms, and/or 1 to 4 nitrogen atoms in the ring, and may be bonded to the remainder of the molecule through a carbon or heteroatom. Exemplary heteroaromatics include furyi, thienyl, pyridyl, oxazoiyi, pyrrotyl, indoiyi, quinolinyl, or isoquinoiinyl and the like. Exemplary substituents include one or more of the following groups: hydrocarfayl, substituted hydrocarbyl, keto, hydroxy, protected hydroxy, acyl, acyloxy, alkoxy, alkenoxy, aikynoxy, aryloxy, halogen, amido, amino, nitre, cyano, thiol, ketals, acetals, esters and e^ers. The temi "acyl," as used herein alone or as part of another group, denotes the moiety formed by removal of tfie hydroxy! group from the group -COOH of an oR9anic carboxyiic acid, e.g., RC(0>, wherein R is R\ R^O-, R^R^N-, or R^S-, R' is hydrocarbyl, heterosubstituted hydrocarbyl, or heterocyclo, and R^ is hydrogen, hydrocarbyl or substituted hydrocarbyl. The temi "acyloxy," as used herein alone or as part of another group, denotes an acyl group as described above bonded through an oxygen linkage (—0-), e.g., RC(0)0- wherein R is as defined in connection with the term "acyl." Unless otherwise indicated, the alkoxycarbonyloxy moieties described herein comprise lower hydrocarbon or substituted hydrocarbon or substituted hydrocarbon moieties. Unless otherwise indicated, the carbamoyloxy moieties described herein are derivatives of carbamic acid in which one or both of the amine hydrogens is optionally replaced by a hydrocarbyl, substituted hydrocarbyl or heterocyclo moiety. The terms "hydnDxyl protecting group" and "hydroxy protecting group" as used herein denote a group capable of protecting a free hydroxyl group {"protected hydroxyl") which, subsequent to the reaction for which protection is employed, may be removed without disturbing the remainder of the molecule. A variety of pnstecting groups for the hydroxyl group and the synthesis thereof may be found in "Protective Groups in OR9anic Synthesis" by T. W. Greene, John Wiley and Sons, 1981, or Fieser & Fieser. Exemplary hydroxy! protecting groups include methoxymethyl, 1-ethoxyethyl, benzyloxymethyl, (.beta.-trimethytsilyiethaxy)methyl, tetrahydropyranyl, 2,2,2-trichloroethoxycarbonyl, t-butyl{diphenyi)silyl, trialkylsilyl, trichloromethoxycarbonyl and 2,2,2-trichioroethoxymethyl. As used herein, "Ac" means acetyl; "Bz" means benzoyl; "Et" means ethyl; "Me" means methyl; "Ph" means phenyl; "iPr" means isopropyl; "tBu" and l-Bu" means tert-butyf; "R" means lower alkyt unless othenwise defined; "py" means pyridine or pyridyl; "TES" means triethylsiiyl; "TMS" means trimethylsilyl; "LAH" means lithium aluminum hydride; "lO-DAB" means 10-desacetylbaccatln 111'; "amine protecting group" inciudes. but is not limited to. carbamates, for example, 2,2.2-trichloroethylcarbamate ortertbutyicarbamate; "protected hydroxy" means -OP wherein P is a hydroxy protecting group; "SuOCO" and "Boo" mean tert-butoxycarbonyl; "tAmOCO" means tert-amyloxycarbonyl; '2-FuCO" means 2-furylcarbonyl;'2th' means 2-thieny(; "PhCO" means phenyicarbonyl; '2-ThCO' means 2-thieni^carfaonv^; "2-PyCO" means 2-pyridyicarbonyl; "3-PyCO" means 3-pyridylcarbonyi; "4-PyCO" means 4-pyr1dyicarttonyl; "C4H7CO" means butenyjcarbony); "EtOCO" means ethoxycarbonyl; "ibueCO" means isobutenyicarbonyl; "iBuCO" means isobutylcarbonyl; "iBuOCO" means isobutoxycarbonyl; "iPrOCO" means isopropyloxycarbonyl; "nPrOCO" means n-propyloxycarbonyi; "nPrCO" means n-propy! carbonyl; "ibue" means isobutenyl; THF" means tetrahydrofuran; "DMAP" means 4-di methyl ami no pyridine; "LHMDS" means Lithium HexamethylDiSilazanide. The following examples illustrate the invention. 10-Triethylsi(y(-10-deacety( faaccatin III. To a solution of 1.0 g (1.84 mmoi) of 10-deacefyl baccatin III in 50 mL of THF at-10 "C under a nitrogen atmosphere was added 0.357 mL (2.76 mmol, 1.5 mol equtv) of W,0-(bis)-TES-triffuoroacetamide over a period of 3 min. This was followed by the addition of 0.062 mL of a 0.89 M THF solution of lithium bis{trimethyjsilyl)amide (0.055 mmol, 0.03 mol equiv). After 10 min 0.038 mL {0.92 mmol, 0.5 mol equiv) of methanol was added, and after an additional 5 min 4 mL (0.055 mmol, 0.03 mol equiv) of acetic acid was added. The solution was diluted with 300 mL of ethyl acetate and washed two times with 100 mL of saturated aqueous sodium bicarbonate solution. The combined aqueous layers were extracted with 100 mL of ethyl acetate and the combined oR9anic layers were washed with brine, dried over sodium sul^te, and concentrated under reduced pressure. To the residue was added 100 mL of hexane and the solid (1.23 g, 101 %) was collected by filtration. Recrystaliization of the solid by dissolving in boiling ethyl acetate (20 mL, 17 mUg) and cooling to room temperature gave 1,132 g (94%) of a white solid, m.p. 242 °C; [a]D^-60.4 (C 0.7. CHCI3); 'H NMR {COCl^, 400MHz) 5 (p.p.m): 8.10 (2H, d. Jm - 7.5Hz, Bzo). 7.60 (1H. t, Jm = 7.5Hz. Bzp). 7.47 (2H, t, Jo = 7.5Hz. Bzm), 5.64 (1H. d, J3 = 6.9Hz, H2). 5.26 (1H. s. H10). 4.97 (1H, dd, 76f3 = 2.2Hz, J6c[ = 9.9Hz. H5). 4.85 (1H, dd, J14a = 8.9Hz, J14|3 = 8,9Hz, H13). 4.30 (1H, d. J20P = 8.5Hz, H20a). 4.23 (1H, ddd, J70H = 4.5Hz. J6a = Q.QHz, J63 = II.OH2, H7), 4.15 (1H. d, J20a = 8.5Hz, H203). 4.00 (1H, d, J2 = 6.9Hz, H3), 2.58 (1H, ddd, J7 = 6.6H2. J5 = 9.9Hz, J6p = 14.5Hz, H6a), 2.28-2.25 (5H, m, 4Ac, H14c(, H14P), 2.02(3H, s, ISMe), 1.97 (1H, d, J7 =4.5Hz, H70H). 1.78 (1H, ddd, J7 = 11.0Hz, J5 = 2.2Hz, JQa - 14.5Hz, H6|3). 1.68 (3H, s, 19Me), 1.56 (1H, s. 0H1). 1.32 (1H. d. J13 = 8.8Hz, 0H13 ), 1.18 (3H, s, 17Me), 1.06 (3H. s, 16Me). 0.98 (9H. t, XH2(TES} = 7.3Hz. CH3(TES)). 0.65 (6H. dq, JCH^fTES) = 7.3Hz, CH2(TES)). 10-TriethyIsilyl-10-deacetyl-7-methoxycarbonyl baccatin III. To a solution of 9.3 g (14,1 mmol) of 10-triethylsiiy!-10-deacetyl baccatin III and 10.35 g (84.6 mmol) of DMAP in 500 mL of dichioromethane at 0 °C under a nitrogen atmosphere was added 2.15 mL (22.7 mmol, 1.5 mol equiv) of methyl chlorofomiate. The mixture was stirred at 0 "C for 4 h, diluted with 300 mL of saturated aqueous ammonium chloride solution and extracted twice with 200 mL of ethyi acetate. The oR9anic layer was washed with 500 mL of 10% aqueous copper sulfate solution, 500 mL of saturated aqueous sodium bicarbonate solution, 100 mL of bfine, dried over sodium sulfate and concentrated under reduced pressure. The crude product was recrystaliized from ethyl acetate to give 8.92 g (88%) of 10-triethylsiJyl-10-deacetyl-7-methoxycart>onyl baccatin II). m.p. 260-262 'C; [a\^^ -54.3 (c 0.89, CHCia); 'H NMR (CDCI3, 500MHz) 5 (ppm): 8.10 (2H, d. Jm = 8.5Hz. Bzo), 7.60 (1H, t. Jm = 8.5Hz. Bzp), 7.47 (2H. t Jo = a.SHz, Bzm), 5.64 (1H, d, J3 == 7.0 Hz, H2). 5.31 (1H, dd, J6a = 7.0Hz, J63 = 10.0 Hz. H7), 5.28 (1H, s. H10). 4.96 (1H. d, J6a = 8.5 Hz, H5). 4.86 (1H. t. JUci = 14.0 Hz. J14P = 7.0 Hz, H13), 4.31 {1K d, J2Q3 = 8.0 Hz, H20a),4.16 (1H, d, J20a = 8.0Hz, H20P), 4.06 (1H, d, J2 = 7.0 Hz. H3). 3.77 (3H, s, OMe) 2.65 (1H, ddd. J7 = 7.0 Hz. J5 = 8.5 Hz. J6P = 10.0 Hz, H6a), 2.29-2.26 (5H, m. 4Ac. H14a. H14P ), 2.08 (3H. s. 18Me). 2.01 (1H. d. 130H), 1.92 (3H. ddd, J7 = 10.0 Hz. J5 = 2.3 Hz. J6a = 10.0 Hz, H6p). 1.80 (3H. s, 19Me). 1.18 (3H, s, 17Me). 1.05 (3H, s, 16Me). 0.97 (9H, t. JCH^CTES) = 8.0 Hz. CHjCTES)). 0.59 (6H, dq, XHafTES) = 8.0Hz, CHjCTES)). 2'-O-MOP-3'Klesphenyl-3'-{2-thienyl)-10-triethylsiIyl-7-methoxycarbonyl taxotere. To a solution of 495 mg (0.690 mmol) of 10-triethylsilyl-10-deacetyl-7-methoxycarbonyl baccatin III in 4 mL of anhydrous THF under a nitrogen atmosphere at -45 °C was added 0.72 mL (0.72 mmoi) of a 1M solution of LiHMDS in THF. After 0.5 h a solution of 278 mg (0.814 mmol) of the b-Lactam in 2 mL of anhydrous THF was added. The mixture was warmed to 0 "C, and . after 2 h 0.5 mL of saturated aqueous sodium bicarbonate solution was added. The mixture was diluted with 50 ml of ethyl acetate and washed two times with 5 mL of brine. The oR9anic phase was dried over sodium sulfate and concentrated under reduced pressure to give a slightly yellow solid. The solid was reaystalllzed by dissolving it in 12 mL of a 1:5 mixture of ethyl acetate and hexane at reflux and then cooling to room temperature to give 679 mg (93%) of a white crystalline solid which was used directly in the next reaction. 3'-Desphenyi-3'-(2-thienyl)-7-methoxycarbonyl taxotere. To a solution of 211 mg (0.199 mmol) of 2'-0-MOP-3'-desphenyi-3'-(2-thienyl)-10-triethylsilyl-7-methoxycarbonyt taxotere in 1.7 mL of pyridine and 5.4 mL of acetonitrile at 0 "C was added 0.80 mL (2.0 mmol) of an aqueous solution containing 49% HF. The mixture was wanned to room temperature for 14 h and was then diluted with 20 mL of ethyl acetate and washed three times with 2 mL of saturated aqueous sodium bicarbonate and then with 8 mL of brine. The oR9anic phase was dried over sodium sulfate and concentrated under reduced pressure to give 174 mg (100%) of a white solid. The crude product was crystallized with 2 mL of solvent (CH2Cl2:hexane=1:1.7) to give 168 mg (97%) of white crystals, m.p. 142.5-143 °C; [a]D^^-25.1 (cO.53. CHO:,); Anal. CaicdforC43H53NOi6S: C, 59.23; H, 6.13. Found: C, 58.99; H. 5.25. 'H NMR (500 MHz. CDCI3): Example 2 The procedures described in Example 1 were repeated, but other suitably protected [J-lactams were substituted for the p-lactam of Example 1 to prepare the series of compounds having structural formula (13) and the combinations of substituents identified in the following table. Example 3 Following the processes described in Example 1 and elsewhere herein, the following specific taxanes having structural formula 14 may be prepared, wherein R? is as previously defined, including wherein R^ is Ryj^OCOO- and R?, is (i) substituted or unsubstituted C, to Cs alkyl (straight, branched or cyclic), such as methyl, ettiyl, propyl, butyl, pentyl, or hexyi; (ii) substituted or unsubstituted Cj to C8 alkenyl (straight branched or cyclic), such as ethenyl, propenyl, butenyl, pentenyi or hexenyl; (iii) substituted or unsubstituted Cj to C8 alkynyl (straight or branched) such as ethynyl, propynyl, butynyl, pentynyl, or hexynyl; (iv) substituted or unsubstituted phenyl; or (v) substituted or unsubstituted heterocycio such as furyt. thienyl, or pyridyl. The substituents may be hydrocarbyl or any of the heteroatom containing substituents selected from the group consisting of heterocycio, alkoxy, alkenoxy, alkynoxy, aryloxy, hydroxy, prtjtected hydroxy, keto, acyloxy, nitro, amino, amido, thiol, ketai, acetal, ester and ether moieties, but not phosphorous containing moieties. Example 4 Following ttie processes described in Example 1 and elsewhere herein, the following specific taxanes having stmctural formula 15 may be prepared, wherein in each of the series (that is, each of series 'A" through "K") Rio is hydroxy and R7 is as previously defined, including wherein R2 is R^^OCOO- and Ry, is (i) substituted or unsubstituted, preferably unsubstituted, C; to C8 alky! (straight, branched or cyclic), such as ethyl, propyl, butyl, pentyl, or hexyt; (ii) substituted or unsubstituted, preferably unsubstituted, C2 to Cj alkenyl (straight, branched or cyclic), such as ethenyi, propenyl, butenyl, pentenyl or hexenyl; (iii) substituted or unsubstrtuted, preferably unsubstituted, Cj to C8 alkynyl {straight or branched) such as ethynyl, propynyi, butynyi, pentynyl, or hexynyl; (iv) substituted or unsubstituted, preferably unsubstituted, pfienyl; or(v) substituted or unsubstrtuted, preferably unsubstituted, heteroaromatic such-as furyl, thienyl. or pyridyl. In the "A" series of compounds, X,o is as othenwise as defined herein. Preferably, heterocyclo is substituted or unsubstitued furyl, thienyl, or pyridyl, X,Q is substituted or unsubstitued furyl, thienyl, pyridyl. phenyl, or lower alkyl (e.g., tert-butyi), and R7 and R^Q each have the beta stereochemical configuration. In the "B" series of compounds, X^Q and R^^ are as otherwise as defined herein. Preferably, heterocyclo is preferably substituted or unsubstitued furyl, thienyl, or pyridyl, X^Q is preferably substituted or unsubstitued furyl, thienyl, pyridyl, phenyl, or lower alkyl (e.g., tert-butyl), R7a is preferably substituted or unsubstitued furyl, thienyl, pyridyl, phenyl, or lower alkyl, and R^ and R^Q each have the beta stereochemical configuration. In the "C series of compounds, K^^ and R9a are as otherwise as defined herein. Preferably, heterocyclo is preferably substituted or unsubstitued furyl, thienyl, or pyridyl, X,o is preferably substituted or unsubstitued furyl, thienyl, pyridyl, phenyl, or lower alkyl (e.g., tert-butyl), R9^ is preferably substituted or unsubstitued furyl, thienyl, pyridyl, phenyl, or lower alkyl, and R,, R9 and R^^ each have the beta stereochemical configuration. In the "D" and "E" series of compounds, X^Q is as othenA/ise as defined herein. Preferably, heterocyclo is preferably substituted or unsubstitued fury!, thienyl, or pyridyl, X10 is preferably substituted or unsubstitued furyl, thienyl, pyridyl, phenyl, or lower alkyl (e.g., tert-butyl), and R^, R9 (series D only) and R^^ each have the beta stereochemical configuration. In the "F' series of compounds, Xm, R7a and R9a are as otherwise as defined herein. Preferably, heterocyclo is preferably substituted or unsubstitued fijryl, thienyl. or pyridyl, X,Q is preferably substituted or unsubstitued furyl, thienyl, pyridyl. phenyl, or lower alkyl (e.g., tert-butyl), R2a is preferably substituted or unsubstitued furyl, thienyl, pyridyl. phenyl, or lower alkyl, and R^. R9 and R,(, each have the beta stereochemical configuration. in the "G' series of compounds, X^j and R^^ are as otherwise as defined herein. Preferably, heterocyclo is preferably substituted or unsubstitued fijryl, thienyl, or pyridyl, X^o is preferably substituted or unsubstitued furyl. thienyl. pyridyl, phenyl, or lower alkyl (e.g., tert-butyl), Rza is preferably substituted or unsubstitued furyl, thienyl, pyridyl, phenyl, or lower alkyl, and R^, R9 and R10 each have the beta stereochemical configuration. in the "H" series of compounds, X^^ is as otherwise as defined herein. Preferably, heterocyclo is preferably substituted or unsubstitued furyl, thienyl, or pyridyl, X^p is preferably substituted or unsubstitued furyl, thienyl, pyridyl, phenyl, or lower alkyl (e.g., tert-butyl), R7a 's preferably substituted or unsubstitued ftjry}, thienyl, pyridyl, phenyl, or lower alkyl, and R2 and R^Q each have the beta stereochemical configuration. In the 1" series of compounds, Xu, and R^^ are as otherwise as defined herein. Preferably, heterocyclo is preferably substituted or unsubstitued furyl, thienyl, or pyridyl, X^^ is preferably substituted or unsubstitued furyl, thienyl, pyridyl, phenyl, or lower alkyi (e.g., tert-butyl). R^ is preferably substituted or unsubstitued furyl, thienyl, pyridyl, phenyl, or lower alkyl, and R7 and Rio each have the beta stereochemical configuration. )n the "J" series of compounds, X^j and Rsa are as otherwise as defined herein. Preferably, heterocyclo is preferably substituted or unsubstitued furyl, thienyl, or pyridyl, X^^. 's preferably substituted or unsubstitued furyl, thienyl, pyridyl, phenyl, or lower alkyl (e.g., tert-butyl), R2g Is preferably substituted or unsubstitued furyl, thienyl. pyridyl, phenyl, or lower alkyl, and R?. R9 and R10 each have ihe beta stereochemical configuration. (n the "K" series of compounds, X10, R2j and R^ are as othenwise as defined herein. Preferably, heterocyclo is preferably substituted or unsubstitued furyl, thienyl, or pyridyl, X,£, is preferably substituted or unsubstitued furyl, thienyl, pyrid>^, phenyl, or lower alkyl (e.g., tert-butyl), Ri^ is preferably substituted or unsubstitued furyl, thienyl, pyridyl, phenyl, or lower alkyl, and R,, R9 and R^Q each have the beta stereochemical configuration. Any substituents of each X3. X5. R^, Ry, and R3 may be hydrocarbyl or any of the heteroatom containing substituents selected from the group consisting of heterocyclo, alkoxy, alkenoxy, alkynoxy, aryloxy, hydroxy, protected hydroxy, keto, acyloxy, nitro, amino, amido, thiol, ketal, acetal, ester and ether moieties, but not phosphorous containing moieties. Example 5 in Vitro cytotoxicity measured by the cell colony formation assay Four hundred ceils (HCT116) were plated in 60 mm Petri dishes containing 2.7 mL of medium {modified McCoy's 5a medium containing 10% fetal bovine serum and 100 units/mL penicillin and 100 g/mL streptomycin). The ceils were Incubated in a CO2 incubator at 37 °C for 5 h for attachment to the bottom of Petri dishes. The compounds identified In Example 2 were made up fresh in medium at ten times the final concentration, and then 0.3 mL of this stock solution was added to the 2.7 mL of medium in the dish. The ceils were then incubated with drugs for 72 h ai 37 " C. At the end of Incubation the dnjg-containing media were decanted, the dishes were rinsed with 4 mL of Hank's Balance Salt Solution (HBSS), 5 mL of fresh medium was added, and the dishes were returned to the incubator for coiony formation. The ceil colonies were counted using a colony counter after Incubation for 7 days. Cell survival was calculated and the values of ID50 {the drug concentration producing 50% inhibition of coiony formation) were determined for each tested compound. WE CLAIM: 1. A taxane having the formula R2 is benzoyioxy ; R7 is RT.OCOO-; R10 is hydroxy ; X3 is C1-8.alkcyl, C2-8alkenyl, or heterocyclo ; X3 is-COX10, wherein X10 is phenyl or C2-8alkenyl, or X5 is-COOX10,wherein X10 is C1-8 alkyl; R7a is C|.8 aikyi, phenyl or a 5- or 6-membered heterocycio; and Ac is acetyl. 2. The taxane as claimed in claim 1 wherein X3 is 2-fury[, 3-furyl, 2-thienyi, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, C1-C8 alkyl, or C2-C8 alkenyl. 3. The taxane as claimed in claim 2 wherein X5 is -COX10 and X10 is phenyl, C2-C8 alkenyl, or X5 is -COOX10 and X10 is C1-C8 aikyi. 4. The taxane as claimed in claim 2 wherein X5 is-COX10 atid X10 is phenyl, or X5 is-COOX10 and X10 is t-butyl. 5. The taxane as claimed in claim I wherein X3 is furyl or thienyl. 6. The taxane as claimed in claim 5 wherein X5 is -COX,o and X10 is C2-C2 alkenyl, or X5 is-COOX10 and X10 is C1 - C8 alkyl. -62- 7. The taxane as claimed in claim 5 wherein X5 is -COX10 and X10 is phenyl, or X5 is -COOX10 and X10 is t-butyl. 8. The taxane as claimed in claim 2 wherein X3 is cycloalky). 9. The taxane as claimed in claim 8 wherein X5 is -COX10 and X10 is phenyl, C2 -C8 alkenyl, or X5 is -COOX10 and X10 is C1-C8 alkyl, 10. The taxane as claimed in claim 8 wherein X5 is -COX10 and X10 is phenyl, or X5 is-COOX10 and X10 is t-butyl. 11. The taxane as claimed in claim 2 wherein X3 is isobutenyl. 12. The taxane as claimed in claim 11 wherein X5 is -COX10 and X10 is phenyl, C2-Cg alkenyl, or X3 is-COOX|o and X10 is C1 - C8 alkyl. 13. The taxane as claimed in claim 11 wherein X5 is -COX10 and X10 is phenyl, or X5 is-COOX10 and X10 is t-butyl. 14. The taxane as claimed in claim 1 wherein R7 is RyaOCOO- and R7a is methyl, ethyl or propyl. 15. The taxane as claimed in claim 14 wherein X3 is 2-iliryl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, C1-C8 alkyl, or C2-Cg alkenyl. 16. The taxane as claimed in claim 15 wherein X5 is -COX10 and X10 is phenyl, C2 - C8 alkenyl, or X5 is -COOX10 and X10 is C1C8 alkyl. 17. The taxane as claimed in claim 15 wherein X5 is-COX|o and X10 is phenyl, or X5 is-COOX|o and X10 is t-butyl. • 18. The taxane as claimed in claim 14 wherein X3 is furyl or thienyl. 19. The taxane as claimed in claim 18 wherein X5 is -COX10 and X10 is phenyl, C2-C8 alkeny], or X5 is-COOX,o and X10 is C1-C8 alkyl. 20. The taxane as claimed in claim 18 wherein X5 is -COX10 and X10 is phenyl, or X5 is -COOX10 and X10, is t-butyl. 21. The taxane as claimed in claim 14 wherein X3 is cycloalkyl, 22. The taxane as claimed in claim 21 wherein X3 is -COX10 and X|o is phenyl, Ci-Cg alkenyl, or X5 is-COOX10 and X^o is Ci-Cg alkyl. 23. The taxane as claimed in claim 21 wherein X5 is -COX10 and X10 is phenyl, or X5 is -COOX10 and X10 is t-buiyl. 24. The taxane as claimed in claim 14 wherein X3 is isobutenyl. 25. The taxane as claimed in claim 24 wherein X5 is-COX10 and X10 is phenyl, C2-Cg alkenyl, or X, is-COOX10 and X10 is C, - Cg alkyl, 26. The taxane as claimed in claim 24 wherein X5 is -COX10 and X10 is phenyl, or X5 is-COOX|o and X,o is t-butyl. 27. The taxane as claimed jn claim 1 wherein X3 is furyl or thienyl, R7a is methyl or ethyl, and X5 is-COX10 and X10 is phenyl, or X5 is -COOX10 and X10 is t-butyl. 28. The taxane as claimed in claim 1 wherein X3 is substituted or unsubstituted furyl, R7a is methyl or ethyl, and X5 is -COX10 and X|o is phenyl, or X5 is -COOX|o and X10 is t-butyl. 29. The taxane as claimed in claim 1 wherein X3 is substituted or unsubstituted thieny), R7a is methyl, and X5 is -COX10 and X10 is phenyl, or X5 is -COOX10 and X10 is t-butyl. 30. The taxane as claimed in claim 1 wherein X3 is isobutenyl, R7a is ethyl, and X5 is -COX10and X10 is phenyl, OTX5 is -COOX3aand X,o is t-butyJ. 31. The taxane as claimed in claim 1 wherein X3 is a\ky\, Ry2 is methyl or ethyl, and X5 is -COX10and X10, is phenyl, orX5 is -COOX,oand X10t-butyl. 32. The taxane as claimed in claim 1 wherein X3 is 2-fuiyl or 2-thienyl, R7a is methyl or ethyl, X5 is -COOX;o and X10 is l-butyl, 33. The taxane as claimed in claim 1 wherein X3 is 2-furyl, R7a is methyl or ethyl, X3 is -COOX,o and X10 is l-buiyl. 34. The taxane as claimed in claim 1 wherein X3 is 2-thienyl, R7a is methyl or ethyl, X3 is-COOX10and X10 is l-butyl. 35. The taxane as claimed in claim 1 wherein X3 is isobutenyl. X3 is-COOX10 and X10 is t-butyl. 36. The taxane as claimed in claim 1 wherein X3 is cycloalkyi, R7a is methyl or ethyl, X5 is -COOX10 and X10 is t-butyl. 37. The taxane as claimed in claim I wherein X5 is -COOX10 and X10's isopropyl or isobutyl, X3 is 2-thienyl, and Ry^ is methyl or ethyl. 38. The taxane as claimed in claim 1 wherein X5 is -COOX10 and X10 is t-butyl, X3 is 2-thienyl, and Ria is methyl or ethyl. 39. The taxane as claimed in claim 1 wherein X5 is --COOX10 and X^ is t-butyl, X3 is 3-thienyl, and Ri^ is methyl or ethyl. 40. The taxane as claimed in claim 1 wherein X5 is -COOX10 and X10 is t-butyl or isobutyl, X3 is 2-furyl, and R7s is methyl or ethyl. 41. The taxane as claimed in claim 1 wherein X5 is -COOX10 and X10 is t-butyl or tert-amyl, X3 is 2-furyl, and R7a is benzyl. 42. The taxane as claimed in claim 1 wherein X5 is -COOX10 and X10 is l-buly] or isobutyl, X3 is 3-furyl, and R7a is melhyi or cihyi. 43. The taxane as claimed in claim 1 wherein X5 is -COOX10 and X10 is t-buty or isobutyl, X3 is isobutenyl, and R7a is methyl or ethyl. 44. The taxane as claimed in claim 1 wherein X5 is -COOX10 and Xm is i-buty! or isobutyl, X3 is cyclopropyl, and R^a is melhyi or ethyl. 45. The taxane as claimed in claim 1 wherein X5 is -COX10 and X10 is t-butyl or isobutyl, X3 is 3-lhienyl, and R7a is methyl or ethyl. 46. The taxane as claimed in claim 1 wherein X5 is -COX10 and X10 is t-butyl or isobutyl, X3 is 2-furyi, and R7a, is methyl or ethyl. 47. TTie taxane as claimed in claim 1 wherein X5 is -COXID and Xm is phenyl, trans-propenyl, or isobutenyl, X3 is 2-thienyl, and R7a is methyl or ethyl. 48. The taxane as claimed in claim 1 wherein X5 is -COX10 and X10 is trans-propenyl, X3 is 3-fury!, and R7a is methyl or ethyl. 49. The taxane as claimed in claim 1 wherein X5 is -COX10 and X10 is trans-propenyl, X3 is 2-thieny!, and R7A is benzyl. ' 50. The taxane as claimed in claim I wherein X5 is -COX10 and X10 isobutenyl, X3 is 2-furyl, and R7a is ethyl or benzyl. 51. A pharmaceutical composilion comprising the texane as claimed in any of the preceding claims and at least one pharmaceutical composition.

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