Title of Invention	6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS
Abstract	6-MODIfIED BiCYCliC NUClEiC ACiD ANAlOGS The present invention provides 6-modified bicyclic nucleoside analogs and oligomeric compounds comprising these nucleoside analogs. in preferred embodiments the nucleoside analogs have either (R) or (s)-chirality at the 6-position. These bicyclicnucleoside analogs are useful for enhancing properties of oligomeric compounds including nuclease resistance.

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CROSS-REFERENC6TO RELATED APPLICATIONS This application claims priority benefit to U.S. Provisional Application No. 60/762,722, filed January 27, 2006 and entitled, "Subsituted Bicyclic Nucleic AC1d Analogs;" and U.S. Provisional Application No. 60/805,660, filed June 23,2006 aad entitled, "6-Substituted Bicyclic Nucleic AC1d Analogs," the entirety of each of these disclosures are incorporated herein by reference. FIELD OF THE INVENTION The present invention provides 6-modified bicyclic nucleosides and oligomeric compounds and compositions prepared therefirom. More particularly, the present invention provides nucleosides having a 2'-0-C(H)(R)-4' bridge and oligomers and compositions prepared therefi-om. In a preferred embodiment, R is in a particular configuration providing either the (R) or (S) isomer. In some embodiments, the oligomeric compounds and compositions of the present invention hybridize to a portion of a target RNA resulting in loss of normal fimction of the target RNA. BACKGROUND OF THE INVENTION Antisense technology is an effective means for reduC1ng the expression of one or more speC1fic gene products and can therefore prove to be xmiquely usefiil in a number of therapeutic, diagnostic, and research applications. Chemically modified nucleosides are routinely used for incorporation into antisense sequences to enhanC6one or more properties such as for example nuclease resistance. One such group of chemical modifications includes bicyclic nucleosides wherein the fiaranose portion of the nucleoside includes a bridge connecting two atoms on the furanose ring thereby forming a bicyclic ring system. Such bicyclic nucleosides have various names including BNA's and LNA's for bicycKc nucleic aC1ds or locked nucleic aC1ds respectively. Various BNA's have been prepared and reported in the patent literature as well as in sC1entific literature, see for example: Singh et al., Chem. Commun., 1998,4,455-456; Koshkin et al., Tetrahedron, 1998, 54,3607-3630; Wahlestedt et al, Proc. Natl. Acad. SC1. U. S. A., 2000, 97, 5633-5638; Kumar et al, Bioorg. Med. Chem. Lett., 1998, 8, 2219-2222; Wengel et al., PCT hitemational Application WO 98-DK393 19980914; Singh et al., J. Org. Chem., 1998, 63, 10035-10039, the text of each is incorporated by referenC6herein, in their entirety. Examples of issued US patents and published appplications include for example: U.S. Patents 7,053,207, 6,770,748, 6,268,490 and 6,794,499 and published U.S. applications 20040219565, 20040014959, 20030207841, 20040192918, 20030224377, 20040143114 and 20030082807; the text of each is incorporated by referenC6herein, in their entirety. Many LNA's are toxic. See, e.g., Swayze, E. E.; Siwkowski, A. M.; Wancewicz, E. V.; Migawa, M. T.; Wyrzykiewicz, T. K.; Hung, G.; Monia, B. P.; Bennett, C. F., Antisense oligonucleotides containing locked nucleic aC1d improve potency but cause significant hepatotoxiC1ty in animals. Nucl. AC1ds Res., doi: 10.1093/nar/gkll071 (Dec. 2006, advanced online publication). Consequently, there remains a long-felt need for agents that speC1fically regulate gene expression via antisense mechanisms. Disclosed herein are 6-substituted BNA's and antisense compounds prepared therefi-om useful for modulating gene expression pathways, including those relying on mechanisms of action such as RNaseH, RNAi and dsRNA enzymes, as well as other antisense mechanisms based on target degradation or target occupancy. One having skill in the art, onC6armed with this disclosure will be able, without undue experimentation, to identify, prepare and exploit antisense compounds for these uses. wherein: Bx is a heterocyclic base moiety; Ti is H or a hydroxyl protecting group; T2 is H, a hydroxyl protecting group or a reactive phosphorus group; Z is C1-C6alkyl, Ca-C6alkenyl, Ca-C6alkynyl, substituted C1-C6alkyl, substituted C2-C6 alkenyl, substituted C2-C6 alkynyl, acyl, substituted acyl, or substituted amide. In one embodiment, each of the substituted groups, is, independently, mono or poly substituted with optionally protected substituent groups independently selected firom halogen, 0x0, hydroxyl, OJ1, NJ1J2, SJ1, N3, OC(=X)J1, OC(=X)NJ1J2, NJ3C(=X)NJ1J2 and CN, wherein each J1, J2 and J3 is, independently, H or C1-C6alkyl, and X is O, S or NJj. In one embodiment, each of the substituted groups, is, independently, mono or poly substituted with substituent groups independently selected from halogen, 0x0, hydroxyl, OJ1, NJ1J2, SJ1, N3, OC(=X)J1, and NJ3C(=X)NJ1J2, wherein each J|, J2 and J3 is, independently, H, C1-C6alkyl, or substituted C1-C6alkyl and X is O or NJ1. In one embodiment, Z is CpC6alkyl or substituted C1-C6alkyl. In another embodiment, Z is C1-C6alkyl. In another embodiment, Z is methyl (CH3-). In another embodiment, Z is ethyl (CH3CH2-). In another embodiment, Z is substituted C1-C6alkyl. In another embodiment, Z is substituted methyl. In another embodiment, Z is substituted ethyl. In one embodiment, the substituent group is C1-C6 alkoxy (e.g., Z is C1-C6alkyl substituted with one or more C1-C6alkoxy). In another embodiment, the C1-C6alkoxy substituent group is CH3O- (e.g., Z is CH3OCH2-). In another embodiment, the C1-C6alkoxy substituent group can be further substituted such as N(J1J2)CH20- (e.g., Z is N(J1J2)CH20CH2-). In another embodiment, the substituent group is halogen (e.g., Z is C1-C6alkyl substituted with one or more halogen). In another embodiment, the halogen substituent group is fluoro (e.g., Z is CH2FCH2-, CHF2CH2- or CF3CH2-). In another embodiment, the substituent group is hydroxyl (e.g., Z is C1-C6alkyl substituted with one or more hydroxyl). In another embodiment, Z is HOCH2-. In another embodiment, Z is CH3-, CH3CH2-, -CH2OCH3, -CH2F or HOCH2-. In one embodiment, the Z group is C1-C6alkyl substituted with one or more X", wherein each X"" is independently OJ1, NJ1J2, SJ,, N3, OC(=X)J1, OC(=X)NJ1J2, NJ3C(=X)NJ]J2 or CN; wherein each J1 J2 and J3 is, independently, H or C1-C6alkyl, and X is O, S or NJ1. In another embodiment, the Z group is C1-C6 alkyl substituted with one or more X", wherein each X" is independently halo (e.g., fluoro), hydroxyl, alkoxy (e.g., CH3O-), substituted alkoxy or azido. In one embodiment, the Z group is -CH2X', wherein X*^ is OJ1, NJ1J2, SJ1, N3, OC(=X)J1, 0C(=X)NJ1J2, NJ3C(=X)NJ1J2 or CN; wherein each J1, J2 and J3 is, independently, H or C1-C6alkyl, and X is O, S or NJ1. In another embodiment, the Z group is -CH2X^ wherein X'^ is halo In one embodiment, eachT1 and T2 is a hydroxyl protecting group. A preferred list of hydroxyl protecting groups includes benzyl, benzoyl, 2,6-dichlorobenzyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, mesylate, tosylate, dimethoxytrityl (DMT), 9-phenylxanthine-9-yl (Pixyl) and 9-(p-methoxyphenyl)xanthine-9-yl (MOX). In one embodimentT1 is a hydroxyl protecting i group selected from acetyl, benzyl, t-butyldimethylsilyl, t-butyldiphenylsilyl and dimethoxytrityl wherein a more preferred hydroxyl protecting group isT1 is 4,4'-dimethoxytrityl. In one embodiment, T2 is a reactive phosphorus group wherein preferred reactive phosphorus groups include diisopropylcyanoethoxy phosphoramidite and H-phosphonate. In one preferred embodimentT1 is 4,4'-dimethoxytrityI and T2 is diisopropylcyanoethoxy I phosphoramidite. wherein Bx is a heterocyclic base moiety; T3 is H, a hydroxyl protecting group, a linked conjugate group or an intemucleoside linking group attached to a nucleoside, a nucleotide, an oligonucleoside, an oligonucleotide, a monomeric subunit or an oligomeric compound; T4 is H, a hydroxyl protecting group, a linked conjugate group or an intemucleoside linking group attached to a nucleoside, a nucleotide, an oligonucleoside, an oligonucleotide, a monomeric subunit or an oligomeric compound; wherein at least one of T3 and T4 is an intemucleoside linking group attached to a nucleoside, a nucleotide, an oligonucleoside, an oligonucleotide, a monomeric subunit or an oligomeric compound; and Z is C1-C6alkyl, C2-C6 alkenyl, Ca-C6alkynyl, substituted C1-C6 alkyl, substituted C2-C6 alkenyl, substituted C1-C6alkynyl, acyl, substituted acyl, or substituted amide. In one embodiment, each of the substituted groups, is, independently, mono or poly substituted with optionally protected substituent groups independently selected from halogen, 0x0, hydroxyl, OJ,, NJ1J2, SJ1, N3, OC(=X)J,, 0C(=X)NJ1J2, NJ3C(=X)NJ1J2 and CN, wherein each J1, J2 and J3 is, independently, H or C1-C6alkyl, and X is O, S or NJ1. In one embodiment, each of the substituted groups, is, independently, mono or poly substituted with substituent groups independently selected from halogen, 0x0, hydroxyl, OJ1, NJ1J2, SJ1, N3, OC(=X)J1, and NJ3C(=X)NJ1J2, wherein each J1 J2 and J3 is, independently, H or C1-C6 alkyl, and X is O or NJ1. In one embodiment, at least one Z is C1-C6alkyl or substituted C1-C6alkyl. In another embodiment, each Z is, independently, C1-C6alkyl or substituted C1-C6alkyl. In another embodiment, at least one Z is C1-C6alkyl. In another embodiment, each Z is, independently, C1-C6alkyl. In another embodiment, at least one Z is methyl. In another embodiment, each Z is methyl. In another embodiment, at least one Z is ethyl. In another embodiment, each Z is ethyl. In another embodiment, at least one Z is substituted C1-C6 alkyl. In another embodiment, each Z is, independently, substituted C1-C6alkyl. In another embodiment, at least one Z is substituted methyl. In another embodiment, each Z is substituted methyl. In another embodiment, at least one Z is substituted ethyl. In another embodiment, each Z is substituted ethyl. In one embodiment, at least one substituent group is C1-C6alkoxy (e.g., at least one Z is C1-C6alkyl substituted with one or more C1-C6 alkoxy). In another embodiment, each substituent group is, independently, C1-C6alkoxy (e.g., each Z is, independently, C1-C6alkyl substituted with one or more C1 -C6 alkoxy). In one embodiment, at least one C1-C6alkoxy substituent group is CH3O- (e.g., at least one Z is CH3OCH2-). In another embodiment, each C1-C6alkoxy substituent group is CH3O-(e.g., each Z is CH3OCH2-). In one embodiment, at least one substituent group is halogen (e.g., at least one Z is C1-C6 alkyl substituted with one or more halogen). In another embodiment, each substituent group is, independently, halogen (e.g., each Z is, independently, C1-C6 alkyl substituted with one or more halogen). In another embodiment, at least one halogen substituent group is fluoro (e.g., at least one Z is CH2FCH2-, CHF2CH2- or CF3CH2-). In another embodiment, each halo substituent group is fluoro (e.g., each Z is, independently, CH2FCH2-, CHF2CH2- or CF3CH2-). In one embodiment, at least one substituent group is hydroxyl (e.g., at least one Z is C1-C6alkyl substituted with one or more hydroxyl). In another embodiment, each substituent group is, independently, hydroxyl (e.g., each Z is, independently, C1-C6alkyl substituted with one or more hydroxyl). In another embodiment, at least one Z is HOCH2-. In another embodiment, each Z is HOCH2-. In one embodiment, at least one Z is CH3-, CH3CH2-, CH2OCH3-, CH2F- or HOCH2-. In another embodiment, each Z is, independently, CH3-, CH3CH2-, CH2OCH3-, CH2F- or HOCH2-. In one embodiment, at least one Z group is C1-C6 alkyl substituted with one or more X", wherein each X" is, independently, OJ1, NJ1J2, SJ1, N3, OC(=X)J1, OC(=X)NJ1J2, NJ3C(=X)NJ1J2 or CN; wherein each J1, J2 and J3 is, independently, H or C1-C6alkyl, and X is O, S or NJ1. In another embodiment, at least one Z group is C1-C6alkyl substituted with one or more X", wherein each X^ is, independently, halo (e.g., fluoro), hydroxyl, alkoxy (e.g., CH3O-) or azido. In one embodiment, each Z group is, independently, C1 -C6alkyl substituted with one or more X^ wherein each X" is independently OJ1, NJ1J2, SJ1, N3, OC(=X)J1, 0C(=X)NJ1J2, NJ3C(=X)NJ1J2 or CN; wherein each J], J2 and J3 is, independently, H or C1-C6alkyl, and X is O, SorNJ1. In another embodiment, each Z group is, independently, C1-C6alkyl substituted with one or more X", wherein each X" is independently halo (e.g., fluoro), hydroxyl, alkoxy (e.g., CH3O-) or azido. In one embodiment, at least one Z group is -CH2X', wherein X" is OJ1, NJ1J2, SJ1, N3, OC(=X)J1, 0C(=X)NJ1J2, NJ3C(=X)NJ1J2 or CN; wherein each J1, J2 and J3 is, independently, H or C1-C6alkyl, and X is O, S or NJ). In another embodiment, at least one Z group is -CH2X^, wherein X" is halo (e.g., fluoro), hydroxyl, alkoxy (e.g., CH3O-) or azido. In one embodiment, each Z group is, independently, -CH2X', wherein each X" is, independendy, OJ1, NJ1J2, SJ,, N3, OC(=X)J,, 0C(=X)NJ1J2, NJ3C(=X)NJ1J2 or CN; wherein each J1, J2 and J3 is, independently, H or C1-C6aUcyl, and X is O, S or NJ1. In another embodiment, each Z group is, independently, -CH2X', wherein each X" is, independently, halo (e.g., fluoro), hydroxyl, alkoxy (e.g., CH3O-) or azido. In one embodiment, at least one Z is CH3-. In another embodiment, each Z is, CH3-. In one embodiment, the Z group of at least one monomer is in the (i?)- configuration represented by the formula: In another embodiment, the Z group of each monomer of the formula is in the (S)-configuration. In one embodiment, T3 is H or a hydroxyl protecting group. In another embodiment T4 is H or a hydroxyl protecting group. In a further embodiment T3 is an intemucleoside linking group attached to a nucleoside, a nucleotide or a monomeric subunit. In another embodiment T4 is an intemucleoside linking group attached to a nucleoside, a nucleotide or a monomeric subunit. In another embodiment T3 is an intemucleoside linking group attached to an oligonucleoside or an oUgonucleotide. In a further embodiment T4 is an intemucleoside linking group attached to an oligonucleoside or an oligonucleotide. In one embodiment T3 is an ) intemucleoside linking group attached to an oligomeric compound. In a further embodiment T4 is an intemucleoside linking group attached to an oligomeric compound. In an even further embodiment at least one of T3 and T4 comprises an intemucleoside linking group selected from phosphodiester or phosphorothioate. In one embodiment, oligomeric compounds have at least one region of at least two i contiguous monomers of the formula: In another embodiment, the oligomeric compound comprises at least two regions of at least two contiguous monomers of the above formula. In a further embodiment the oligomeric compound comprises a gapped oligomeric compound. In another embodiment the oligmeric compound comprises at least one region of from about 8 to about 14 contiguous i3-D-2'-deoxyribofuranosyl nucleosides. In a further embodiment the ohgomeric compound comprises at least one region of from about 9 to about 12 contiguous C-D-2'-deoxyribofuranosyl nucleosides. In one embodiment, the oligomeric compound comprises at least one region of from 2 to three contiguous monomers of the above formula, an optional second region of 1 or 2 contiguous 5 monomers of the above formula and a third region of from 8 to 14 fi-D-2'-deoxyriboftiranosyl nucleosides vi'herein the third region is located betv^^een the first and the second regions. In another embodiment the oligomeric compond comprises from 8 to 10 fi-D-2'-deoxyribofiiranosyl nucleosides. In another embodiment of the present invention oligomeric compounds are provided ) having from about 8 to about 40 nucleosides and/or modified nucleosides or mimetiC6 in length. In a ftirther embodiment oligomeric compound comprise from about 8 to about 20 nucleosides and/or modified nucleosides or mimetiC6 in length. In an even fiirther embodiment oligomeric compounds comprise from about 10 to about 16 nucleosides and/or modified nucleosides or mimetiC6 in length. In another embodiment oligomeric compounds comprise from about 10 to ' about 14 nucleosides and/or modified nucleosides or mimetiC6 in length. Also provided are methods of inhibiting gene expression comprising contacting one or more cells, aT1ssue or an animal with an oligomeric compound of the invention. DETAILED DESCRIPTION OF THE INVENTION The present invention provides 6-modified bicyclic nucleosides, oligomeric compoimds and compositions prepared therefrom, novel synthetic intermediates, and methods of preparing the nucleosides, oligomeric compounds, compositions, and novel synthetic intermediates. More particularly, the present invention provides nucleosides having a bridge between the 4' and 2'-positions of the ribose portion having the formula: 2'-0-C(H)(Z)-4' and oligomers and compositions prepared therefrom. In a preferred embodiment, Z is in a particular configuration providing either the (i?) or (5) isomo:. In some embodiments, the oligomeric compounds and compositions of the present invention are designed to hybridize to a portion of a target RNA. In another embodiment, the oligomeric compounds of the present invention can be used in the design of aptamers which are oligomeric compounds capable of binding to aberrant proteins in an in vivo setting. Bicyclic nucleosides of the present invention are useful for enhanC1ng desired properties of oligomeric compounds in which they are incorporated. The oligomers of the present invention may also be useful as primers and probes in diagnostic applications. In a preferred wherein the groups surrounded by broken lined boxes are variable. The group at the 6 postion can also be prepared in the S configuration (note that the R and S designations may vary dependent on the groups at the variable positions). The bicyclic nucleoside monomer shown is generically referred to as a dimethoxytrityl phosphoramidite or more formally using lUPAC naming nomenclature as (lS',3^,4i?,6i?,75)-7-[2-cyanoethoxy(diisopropylamino)phosphinoxy]-l-(4,4'-dimethoxytrityloxymethyl)-3-(uraC1l-l-yl)-6-methyl-2,5-dioxa-bicyclo[2.2.1]heptane. The 6-modified bicyclic nucleosides of the present invention are useful for modifying otherwise unmodified oligomeric compounds at one or more positions. Such modified oligomeric compounds can be described as having a particular motif. Motifs amenable to the present invention include but are not limited to a gapped motif, a hemimer motif, a blockmer motif, a fiilly modified motif, a positionally modified motif and an altemating motif In conjunction with these motifs a wide variety of linkages can also be used including but not limited to phosphodiester and phosphorothioate linkages used uniformly or in combinations. The positioning of 6-modified bicyclic nucleosides and the use of linkage strategies can be easily optimized for the best activity for a particular target. Representative U.S. patents that teach the preparation of representative motifs include, but are not limited to, 5,013,830; 5,149,797; 5,220,007; 5,256,775; 5,366,878; 5,403,711; 5,491,133; 5,565,350; 5,623,065; 5,652,355; 5,652,356; and 5,700,922, certain of which are commonly owned with the instant application, and each of which is herein incorporated by referenC6in its entirety. Motifs are also disclosed in hitemational Applications PCT/US2005/019219, filed June 2, 2005 and published as WO 2005/121371 on December 22, 2005 and PCT/US2005/019220, filed June 2, 2005 and published as WO 2005/121372 on December 22, 2005; each of which is incorporated by referenC6herein in its entirety. The terms "stable compound" and "stable structure" are meant to indicate a compound that is suffiC1ently robust to survive isolation to a usefiil degree of purity fi-om a reaction mixture, and formulation into an efficaC1ous therapeutic agent. Only stable compounds are contemplated herein. Selected substituents within the compotmds described herein are present to a recursive degree. In this context, "recursive substituent" means that a substituent may reC1te another instanC6of itself Because of the recursive nature of such substituents, theoretically, a large number may be present in any given clahn. One of ordinary skill in the art of mediC1nal chemistry and organic chemistry understands that the total number of such substituents is reasonably limited by the desired properties of the compound intended. Such properties include, by way of example and not limitation, physical properties such as molecular weight, solubility or log P, application properties such as activity against the intended target, and practical properties such as ease of synthesis. Recursive substituents are an intended aspect of the invention. One of ordinary skill in the art of mediC1nal and organic chemistry understands the versatility of such substituents. To the degree that recursive substituents are present in a claim of the invention, the total number will be determined as set forth above. The term "alkyl," as used herein, refers to a saturated straight or branched hydrocarbon radical containing up to twenty four carbon atoms. Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, butyl, isopropyl, n-hexyl, octyl, decyl, dodecyl and the like. Alkyl groups typically include from 1 to about 24 carbon atoms, more typically from 1 to about 12 carbon atoms (C1-C12 alkyl) with from 1 to about 6 carbon atoms being more preferred. The term "lower alkyl" as used herein includes from 1 to about 6 carbon atoms. Alkyl groups as used herein may optionally include one or more fiirther substitutent groups. The term "alkenyl," as used herein, refers to a sfraight or branched hydrocarbon chain radical containing up to twenty four carbon atoms and having at least one carbon-carbon double bond. Examples of alkenyl groups include, but are not limited to, ethenyl, propenyl, butenyl, 1 -methyl-2-buten-l-yl, dienes such as 1,3-butadiene and the like. Alkenyl groups typically include from 2 to about 24 carbon atoms, more typically from 2 to about 12 carbon atoms with from 2 to about 6 carbon atoms being more preferred. Alkenyl groups as used herein may optionally include one or more ftirther substitutent groups. The term "alkynyl," as used herein, refers to a straight or branched hydrocarbon radical containing up to twenty four carbon atoms and having at least one carbon-carbon triple bond. Examples of alkynyl groups include, but are not limited to, ethynyl, 1-propynyl, 1-butynyl, and the like. Alkynyl groups typically include from 2 to about 24 carbon atoms, more typically from 2 to about 12 carbon atoms with from 2 to about 6 carbon atoms being more preferred. Alkynyl groups as ixsed herein may optionally include one or more fiarther substitutent groups. The term "aminoalkyl" as used herein, refers to an amino substituted alkyl radical. This term is meant to include C1-C12 alkyl groups having an amino substituent at any position and wherein the alkyl group attaches the aminoalkyl group to the parent molecule. The alkyl and/or amino portions of the aminoalkyl group can be further substituted with substituent groups. The term "aliphatic," as used herein, refers to a sfraight or branched hydrocarbon radical containing up to twenty four carbon atoms wherein the saturation between any two carbon atoms is a single, double or triple bond. An aliphatic group preferably contains from 1 to about 24 carbon atoms, more typically from 1 to about 12 carbon atoms with from 1 to about 6 carbon atoms being more preferred. The straight or branched chain of an aliphatic group may be interupted with one or more heteroatoms that include nitrogen, oxygen, sulftir and phosphorus. Such aliphatic groups interupted by heteroatoms include without limitation polyalkoxys, such as polyalkylene glycols, polyamines, and polyimines. Aliphatic groups as used herein may optionally include further substitutent groups. The term "alicyclic" or "alicyclyl" refers to a cyclic ring system wherein the ring is aliphatic. The ring system can comprise one or more rings wherein at least one ring is aliphatic. Preferred aiicyC1iC6 include rings having from about 5 to about 9 carbon atoms in the ring. Alicyclic as used herein may optionally include further substitutent groups. I The term "alkoxy," as used herein, refers to a radical formed between an alkyl group and an oxygen atom wherein the oxygen atom is used to attach the alkoxy group to a parent molecule. Examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-hvAoxy, n-pentoxy, neopentoxy, n-hexoxy and the like. Alkoxy groups as used herein may optionally include further substitutent groups. The terms "halo" and "halogen," as used herein, refer to an atom selected from fluorine, chlorine, bromine and iodine. The terms "aryl" and "aromatic," as used herein, refer to a mono- or polycycUc carbocyclic ring system radicals having one or more aromatic rings. Examples of aryl groups include, but are not limited to, phenyl, naphthyl, tetrahydronaphthyl, indanyl, idenyl and the like. Preferred aryl ring systems have from about 5 to about 20 carbon atoms in one or more rings. Aryl groups as used herein may optionally include further substitutent groups. The terms "aralkyl" and "arylalkyl," as used herein, refer to a radical formed between an alkyl group and an aryl group wherein the alkyl group is used to attach the aralkyl group to a parent molecule. Examples include, but are not limited to, benzyl, phenethyl and the like. Aralkyl groups as used herein may optionally include fiirther substitutent groups attached to the alkyl, the aryl or both groups that form the radical group. The term "heterocyclic radical" as used herein, refers to a radical mono-, or poly-cyclic ring system that includes at least one heteroatom and is unsaturated, partially saturated or fully saturated, thereby including heteroaryl groups. Heterocyclic is also meant to include ftised ring systems wherein one or more of the fused rings contain at least one heteroatom and the other rings can contain one or more heteroatoms or optionally contain no heteroatoms. A heterocyclic group typically includes at least one atom selected from sulfur, nifrogen or oxygen. Examples of heterocycHc groups include, [1,3]dioxolane, pyrrolidinyl, pyrazolinyl, pyrazolidinyl, unidazolinyl, imidazolidinyl, piperidinyl, piperazinyl, oxazolidinyl, isoxazolidinyl, morpholinyl. thiazolidinyl, isothiazolidinyl, quinoxalinyl, pyridazinonyl, tetrahydrofuryl and the like. Heterocyclic groups as used herein may optionally include further substitutent groups. The terms "heteroaryl," and "heteroaromatic," as used herein, refer to a radical comprising a mono- or poly-cyclic aromatic ring, ring system or fused ring system wherein at i least one of the rings is aromatic and includes one or more heteroatom. Heteroarylis also meant to include fused ring systems including systems where one or more of the fused rings contain no heteroatoms. Heteroaryl groups typically include one ring atom selected from sulfur, nitrogen or oxygen. Examples of heteroaryl groups include, but are not limited to, pyridinyl, pyrazinyl, pyrimidinyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, isooxazolyl, thiadiazolyl, I oxadiazolyl, thiophenyl, furanyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzooxazolyl, quinoxalinyl, and the like. Heteroaryl radicals can be attached to a parent molecule directly or through a linking moiety such as an aliphatic group or hetero atom. Heteroaryl groups as used herein may optionally include further substitutent groups. The term "heteroarylalkyl," as used herein, refers to a heteroaryl group as previously defined having an alky radical that can attach the heteroarylalkyl group to a parent molecule. Examples include, but are not limited to, pyridinylmethyl, pyrimidinylethyl, napthyridinylpropyl and the like. Heteroarylalkyl groups as used herein may optionally include further substitutent groups on one or both of the heteroaryl or alkyl portions. The term "mono or poly cyclic structure" as used in the present invention includes all ring systems that are single or polycyclic having rings that are fused or linked and is meant to be inclusive of single and mixed ring systems individually selected from aliphatic, alicyclic, aryl, heteroaryl, aralkyl, arylalkyl, heterocyclic, heteroaryl, heteroaromatic, heteroarylalkyl. Such mono and poly cyclic structures can contain rings that are uniform or have varying degrees of saturation including fully saturated, partially saturated or fully unsaturated. Each ring can comprise ring atoms selected from C, N, O and S to give rise to heterocycHc rings as well as rings comprising only C ring atoms which can be present in a mixed motif such as for example benzimidazole wherein one ring has only carbon ring atoms and the fused ring has two nitrogen atoms. The mono or poly cyclic structures can be further substituted with substituent groups such as for example phthalimide which has two =0 groups attached to one of the rings. In another aspect, mono or poly cyclic structures can be attached to a parent molecule directly through a ring atom, through a substituent group or a bifunctional linking moiety. The term "acyl," as used herein, refers to a radical formed by removal of a hydroxyl group from an organic aC1d and has the general formula -C(0)-X where X is typically aliphatic, alicyclic or aromatic. Examples include aliphatic carbonyls, aromatic carbonyls, aliphatic sulfonyls, aromatic sulfinyls, aliphatic sulfinyls, aromatic phosphates, aliphatic phosphates and the like. Acyl groups as used herein may optionally include further substitutent groups. The term "hydrocarbyl includes groups comprising C, O and H. Included are straight, branched and cyclic groups having any degree of saturation. Such hydrocarbyl groups can ) include one or more heteroatoms selected from N, O and S and can be further mono or poly substituted with one or more substituent groups. The terms "substituent" and "substituent group," as used herein, are meant to include groups that are typically added to other groups or parent compounds to enhanC6desired properties or give desired effects. Substituent groups can be protected or unprotected and can be I added to one available site or to many available sites in a parent compound. Substituent groups may also be further substituted with other substituent groups and maybe attached directly or via a linking group such as an alkyl or hydrocarbyl group to a parent compound. Such groups include without limitation, halogen, hydroxyl, alkyl, alkenyl, alkynyl, acyl (-C(O)Raa), carboxyl (-C(O)O-Raa), aliphatic groups, alicyclic groups, alkoxy, substituted oxy (-0-Raa), aryl, aralkyl, heterocyclic, heteroaryl, heteroarylalkyl, amino (-NRbbRcc). imino(=NRbb), amido (-C(0)N-RbbRco or -N(Rbb)C(0)Raa), azido (-N3), nitro (-NO2), cyano (-CN), carbamide (-0C(0)NRbbRcc or -N(Rbb)C(0)ORaa), ureido (-N(Rbb)C(0)NRbbRco), thioureido (-N(Rbb)C(S)NRbbRcc), guanidinyl (-N(Rbb)C(=NRbb)NRbbRcc), amidinyl (-C(=NRbb)NRbbRcc or -N(Rbb)C(NRbb)Raa), thiol (-SRbb), sulfinyl (-S(O)Rbb), sulfonyl (-S(0)2Rbb), sulfonamidyl (-S(0)2NRbbRoc or -N(Rbb)-S(0)2Rbb) and conjugate groups. Wherein each Raa, Rbb and Rco is, independently, H, an optionally linked chemical functional group or a further substituent group with a preferred list including without Hmitation H, alkyl, alkenyl, alkynyl, aliphatic, alkoxy, acyl, aryl, aralkyl, heteroaryl, alicyclic, heterocycUc and heteroarylalkyl. The term "0x0" refers to the group (=0). The compounds (e.g., bicyclic nucleosides) described herein can be prepared by any of the applicable techniques of organic synthesis, as, for example, illustrated in the examples below. Many such techniques are well known in the art. However, many of the known techniques are elaborated in Compendium of Organic Synthetic Methods (John Wiley & Sons, New York) Vol. 1, lanT. Harrison and Shuyen Harrison (1971); Vol. 2, Ian T. Harrison and Shuyen Harrison (1974); Vol. 3, Louis S. Hegedus and Leroy Wade (1977); Vol. 4, Leroy G. Wade Jr., (1980); Vol. 5, Leroy G. Wade Jr. (1984); and Vol. 6, Michael B. Smith; as well as March, J., Advanced Organic Chemistry, 3rd Edition, John Wiley & Sons, New York (1985); Comprehensive Organic Synthesis. Selectivity, Strategy & EffiC1ency in Modern Organic Chemistry, In 9 Volumes, Barry M. Trost, Editor-in-Chief, Pergamon Press, New York (1993); Advanced Organic Chemistry, Part B: Reactions and Synthesis, 4th Ed.; Carey and Sundberg; Klluwer Academic/Plenum Publishers: New York (2001); Advanced Organic Chemistry, Reactions, Mechanisms, and Structure, 2nd Edition, March, MC6raw Hill (1977); Protecting Groups in Organic Synthesis, 2nd Edition, Greene, T.W., and Wutz, P.G.M., John Wiley & Sons, New York (1991); and 5 Comprehensive Organic Transformations, 2nd Edition, Larock, R.C., John Wiley & Sons, New York (1999). In one aspect of the present invention oligomeric compounds are modified by covalent attachment of one or more conjugate groups. In general, conjugate groups modify one or more properties of the attached oligomeric compound including but not limited to pharmakodynamic, ) pharmacokinetic, binding, absorption, cellular distribution, cellular uptake, charge and clearance. Conjugate groups are routinely used in the chemical arts and are linked directly or via an optional linking moiety or linking group to a parent compound such as an oligomeric compound. A preferred list of conjugate groups includes without limitation, intercalators, reporter molecules, polyamines, polyamides, polyethylene glycols, thioethers, polyethers, cholesterols, i thiocholesterols, cholic aC1d moieties, folate, lipids, phospholipids, biotin, phenazine, phenanthridine, anthraquinone, adamantane, acridine, fluoresceins, rhodamines, coumarins and dyes. LinlC1ng groups or bifonctional Unking moieties such as those known in the art are amenable to the present invention. Linking groups are useful for attachment of chemical I functional groups, conjugate groups, reporter groups and other groups to selective sites in a parent compound such as for example an oligomeric compound. In general a bifunctional linking moiety comprises a hydrocarbyl moiety having two functional groups. One of the functional groups is selected to bind to a parent molecule or compound of interest and the other is selected to bind essentially any selected group such as a chemical functional group or a conjugate group. In some embodiments, the linker comprises a chain structure or an oHgomer of repeating units such as ethylene glyol or amino aC1d units. Examples of functional groups that are routinely used in bifunctional linking moieties include, but are not limited to, electrophiles for reacting with nucleophilic groups and nucleophiles for reacting with electrophilic groups. In some embodiments, bifunctional linking moieties include amino, hydroxyl, carboxylic aC1d, thiol, unsaturations (e.g., double or triple bonds), and the like. Some nonlimiting examples of bifiinctional linking moieties include 8-amino-3,6-dioxaoctanoic aC1d (ADO), sucC1nimidyl 4-(N-maleimidomethyl) cyclohexane-1 -carboxylate (SMCC) and 6-aminohexanoic aC1d (AHEX or AHA). Other linking groups include, but are not limited to, substituted C1-C1o alkyl, substituted or unsubstituted C2-C10 alkenyl or substituted or unsubstituted C2-C10 alkynyl, wherein a nonlimiting list of preferred substituent groups includes hydroxyl, amino, alkoxy, carboxy, benzyl, phenyl, nitre, thiol, thioalkoxy, halogen, alkyl, aryl, alkenyl and alkynyl. The term "protecting group," as used herein, refers to a labile chemical moiety which is known in the art to protect reactive groups including without limitation, hydroxyl, amino and > thiol groups, against undesired reactions during synthetic procedures. Protecting groups are typically used selectively and/or orthogonally to protect sites during reactions at other reactive sites and can then be removed to leave the unprotected group as is or available for further reactions. Protecting groups as known in the art are described generally in Greene and Wuts, Protective Groups in Organic Synthesis, 3rd edition, John Wiley & Sons, New York (1999). ) Groups can be selectively incoiporated into oligomeric compounds of the invention as precursors. For example an amino group can be placed into a compound of the invention as an azido group that can be chemically converted to the amino group at a desired point in the synthesis. Generally, groups are protected or present as precursors that will be inert to reactions that modify other areas of the parent molecule for conversion into their final groups at an i appropriateT1me. Further representative protecting or precursor groups are discussed in Agrawal, et al.. Protocols for Oligonucleotide Conjugates, Eds, Humana Press; New Jersey, 1994; Vol. 26 pp. 1-72. Examples of hydroxyl protecting groups include, but are not limited to, acetyl, t-butyl, t-butoxymethyl, methoxymethyl, tetrahydropyranyl, 1-ethoxyethyl, l-(2-chloroethoxy)ethyl, p- I chlorophenyl, 2,4-dinitrophenyl, benzyl, 2,6-dichlorobenzyI, diphenylmethyl, p-nitrobenzyl, bis(2-acetoxyethoxy)methyl (ACE), 2-trimethylsilylethyl, trimethylsilyl, triethylsilyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, triphenylsilyl, [(triisopropylsilyl)oxy]methyl (TOM), benzoylformate, chloroacetyl, trichloroacetyl, trifluoroacetyl, pivaloyi, benzoyl, p-phenylbenzoyl, 9-fluorenylmethyl carbonate, mesylate, tosylate, triphenylmethyl (trityl), monomethoxytrityl, dimethoxytrityl (DMT), trimethoxytrityl, l(2-fluorophenyl)-4-methoxypiperidin-4-yl (FPMP), 9-phenylxanthine-9-yl (Pixyl) and 9-(p-methoxyphenyl)xanthine-9-yl (MOX). Where more preferred hydroxyl protecting groups include, but are not limited to, benzyl, 2,6-dichlorobenzyl, t-butyldimethylsilyl, t-butyl¬diphenylsilyl, benzoyl, mesylate, tosylate, dimethoxytrityl (DMT), 9-phenylxanthine-9-yl (Pixyl) and 9-(p-methoxyphenyl)xanthine-9-yl (MOX). Examples of amino protecting groups include, but are not limited to, carbamate-protecting groups, such as 2-trimethylsilylethoxycarbonyl (Teoc), l-methyl-l-(4-biphenylyl)-ethoxycarbonyl (Bpoc), t-butoxycarbonyl (BOC), allyloxycarbonyl (Alloc), 9-fluorenylmethyloxycarbonyl (Fmoc), and benzyloxycarbonyl (Cbz); amide-protecting groups, such as formyl, acetyl, trihaloacetyl, benzoyl, and nitrophenylacetyl; sulfonamide-protecting groups, such as 2-nitrobenzenesulfonyl; and imine- and cycHc imide-protecting groups, such as phthaHmido and dithiasucC1noyl. Examples of thiol protecting groups include, but are not limited to, triphenylmethyl i (trityl), benzyl (Bn), and the like. In some preferred embodiments oligomeric compounds are prepared by connecting nucleosides with optionally protected phosphorus containing intemucleoside linkages. Representative protecting groups for phosphorus containing intemucleoside linkages such as phosphodiester and phosphorothioate linkages include (3-cyanoethyl, diphenylsilylethyl, 5-cyanobutenyl, cyano p-xylyl (CPX), N-methyl-N-trifluoroacetyl ethyl (META), acetoxy phenoxy ethyl (APE) and butene-4-yl groups. See for example U.S. Patents Nos. 4,725,677 and Re. 34,069 (P-cyanoethyl); Beaucage, S.L. and Iyer, R.P., Tetrahedron, 49 No. 10, pp. 1925-1963 (1993); Beaucage, S.L. and Iyer, R.P., Tetrahedron, 49 No. 46, pp. 10441-10488 (1993); Beaucage, S.L. and Iyer, R.P., Tetrahedron, 48 No. 12, pp. 2223-2311 (1992). As used herein, the term "orthogonally protected" refers to functional groups which are protected with different classes of protecting groups, wherein each class of protecting group can be removed in any order and in the presenC6of all other classes (see, Barany, G. and Merrifield, R.B., J. Am. Chem. Soc, 1977,99, 7363; idem, 1980,102, 3084.) Orthogonal protection is widely used in for example automated oligonucleotide synthesis. A functional group is deblocked in the presenC6of one or more other protected functional groups which is not affected by the deblocking procedure. This deblocked functional group is reacted in some manner and at some point a further orthogonal protecting group is removed under a different set of reaction conditions. This allows for selective chemistry to arrive at a desired compound or oligomeric compound. The present invention provides compounds having reactive phosphorus groups useful for forming intemucleoside linkages including for example phosphodiester and phosphorothioate intemucleoside linkages. Such reactive phosphorus groups are known in the art and contain phosphoras atoms inP"'orP^ valenC6state including, but not limited to, phosphoramidite, H-phosphonate, phosphate triesters and phosphoms containing chiral auxiUaries. A preferred syn¬thetic soUd phase synthesis utilizes phosphoramidites (P'^' chemistry) as reactive phosphites. The intermediate phosphite compounds are subsequently oxidized to the P^ state using known methods to yield, in preferred embodiments, phosphodiester or phosphorothioate intemucleotide linkages. Additional reactive phosphates and phosphites are disclosed in Tetrahedron Report Number 309 (Beaucage and Iyer, Tetrahedron, 1992,48, 2223-2311). SpeC1fic examples of oligomeric compounds useful in this invention include oligonucleotides containing modified e.g. non-naturally occurring intemucleoside linkages. Two main classes of intemucleoside linkages are defined by the presense or absenC6of a phosphorus atom. Modified intemucleoside linkages having a phosphoms atom include, but are not limited to, phosphorothioates, chiral phosphorothioates, phosphorodithioates, phosphotriesters, aminoalkylphosphotriesters, methyl and other alkyl phosphonates including 3'-alkylene phosphonates, 5'-alkylene phosphonates and chiral phosphonates, phosphinates, phosphoramidates including 3'-amino phosphoramidate and aminoalkylphosphoramidates, thionophosphoramidates, thionoalkylphosphonates, thionoalkylphosphotriesters, selenophosphates and boranophosphates having normal 3-5' linkages, 2'-5' linked analogs of these, and those having inverted polarity wherein one or more interaucleotide linkages is a 3' to 3', 5' to 5' or 2' to 2' linkage. Oligonucleotides having inverted polarity can comprise a single 3' to 3' linkage at the 3'-most interaucleotide linkage i.e. a single inverted nucleoside residue which may be abasic (the nucleobase is missing or has a hydroxyl group in plaC6thereof). Various salts, mixed salts and fi-ee aC1d forms are also included. Representative U.S. patents that teach the preparation of the above phosphorus-containing linkages include, but are not limited to, U.S.: 3,687,808; 4,469,863; 4,476,301; 5,023,243; 5,177,196; 5,188,897; 5,264,423; 5,276,019; 5,278,302; 5,286,717; 5,321,131; 5,399,676; 5,405,939; 5,453,496; 5,455,233; 5,466,677; 5,476,925; 5,519,126; 5,536,821; 5,541,306; 5,550,111; 5,563,253; 5,571,799; 5,587,361; 5,194,599; 5,565,555; 5,527,899; 5,721,218; 5,672,697 and 5,625,050, certain of which are commonly owned with this application, and each of which is herein incorporated by reference. Modified intemucleoside linkages not having a phosphorus atom include, but are not limited to, those that are formed by short chain alkyl or cycloalkyl intemucleoside linkages, mixed heteroatom and alkyl or cycloalkyl intemucleoside linkages, or one or more short chain heteroatomic or heterocyclic intemucleoside linkages. These include those having siloxane backbones; sulfide, sulfoxide and sulfone backbones; formacetyl and thioformacetyl backbones; methylene formacetyl and thioformacetyl backbones; riboacetyl backbones; alkene containing backbones; sulfamate backbones; methyleneimino and methylenehydrazino backbones; sulfonate and sulfonamide backbones; amide backbones; and others having mixed N, O, S and CH2 component parts. Representative U.S. patents that teach the preparation of the above oMgonucleosides include, but are not limited to, U.S.: 5,034,506; 5,166,315; 5,185,444; 5,214,134; 5,216,141; 5,235,033; 5,264,562; 5,264,564; 5,405,938; 5,434,257; 5,466,677; 5,470,967; 5,489,677; 5,541,307; 5,561,225; 5,596,086; 5,602,240; 5,610,289; 5,602,240; 5,608,046; 5,610,289; 5,618,704; 5,623,070; 5,663,312; 5,633,360; 5,677,437; 5,792,608; 5,646,269 and 5,677,439, certain of which are commonly owned with this application, and each of which is herein incorporated by reference. The compounds described herein contain one or more asymmetric centers and thus give rise to enantiomers, diastereomers, and other stereoisomeric forms that may be defined, in terms of absolute stereochemistry, as (R)- or (S)-, a or 13, or as (D)- or (L)- such as for amino aC1ds. The present invention is meant to include all such possible isomers, as well as their racemic and optically pure forms. Optical isomers may be prepared from their respective optically active precursors by the procedures described above, or by resolving the racemic mixtures. The resolution can be carried out in the presenC6of a resolving agent, by chromatography or by repeated crystallization or by some combination of these techniques which are known to those skilled in the art. Further details regarding resolutions can be found in Jacques, et al., Enantiomers, Racemates, and Resolutions (John Wiley & Sons, 1981). When the compounds described herein contain olefinic double bonds, other imsaturation, or other centers of geometric asymmetry, and unless speC1fied otherwise, it is intended that the compounds include both E and Z geometric isomers or C1s- and trans-isomers. Likewise, all tautomeric forms are also intended to be included. The configuration of any carbon-carbon double bond appearing herein is selected for convenienC6only and is not intended to designate a particular configuration unless the text so I states; thus a carbon-carbon double bond or carbon-heteroatom double bond depicted arbitrarily herein as trans may be C1s, trans, or a mixture of the two in any proportion. In the context of the present invention, the term "oHgomeric compound" refers to a polymer having at least a region that is capable of hybridizing to a nucleic aC1d molecule. The term "oUgomeric compound" includes oligonucleotides, oligonucleotide analogs and oligonucleosides as well as nucleotide mimetiC6 and/or mixed polymers comprising nucleic aC1d and non-nucleic aC1d components. OUgomeric compounds are routinely prepared linearly but can be joined or otherwise prepared to be C1rcular and may also include branching. OUgomeric compounds can form double stranded constructs such as for example two strands hybridized to form double stranded compositions. The double stranded compositions can be linked or separate and can include overhangs on the ends. In general, an oUgomeric compound comprises a backbone of linked monomeric subunits where each linked monomeric subunit is directly or indirectly attached to a heterocyclic base moiety. OUgomeric compoxmds may also include monomeric subunits that are not linked to a heterocyclic base moiety thereby providing abasic sites. The linkages ioinine the monomeric subunits. the suear moieties or surrogates and the heterocyclic base moieties can be independently modified. The linkage-sugar unit, which may or may not include a heterocyclic base, may be substituted with a mimetic such as the monomers in peptide nucleic aC1ds. The ability to modify or substitute portions or entire monomers at each position of an oligomeric compound gives rise to a large nxunber of possible motifs. As is known in the art, a nucleoside is a base-sugar combination. The base portion of the nucleoside is normally a heterocyclic base moiety. The two most common classes of such heterocyclic bases are purines and pyrimidines. Nucleotides are nucleosides that fiirther include a phosphate group covalently linked to the sugar portion of the nucleoside. For those nucleosides that include a pentofuranosyl sugar, the phosphate group can be linked to either the 2', 3' or 5' hydroxyl moiety of the sugar. In forming oligonucleotides, the phosphate groups covalently link adjacent nucleosides to one another to form a linear polymeric compound. The respective ends of this linear polymeric structure can be joined to form a C1rcular structure by hybridization or by formation of a covalent bond, however, open linear structures are generally desired. Within the oligonucleotide structure, the phosphate groups are commonly referred to as forming the intemucleoside linkages of the oligonucleotide. The normal intemucleoside linkage of RNA and DNA is a 3' to 5' phosphodiester linkage. In the context of this invention, the term "oligonucleotide" refers to an oligomer or polymer of ribonucleic aC1d (RNA) or deoxyribonucleic aC1d (DNA). This term includes oligonucleotides composed of naturally-occurring nucleobases, sugars and covalent intemucleoside linkages. The term "oligonucleotide analog" refers to oligonucleotides that have one or more non-naturally occurring portions. Such non-naturally occurring oligonucleotides are often desired over naturally occurring forms because of desirable properties such as, for example, enhanced cellular uptake, enhanced affinity for nucleic aC1d target and increased stabiUty in the presenC6of nucleases. In the context of this invention, the term "oHgonucleoside" refers to a sequenC6of nucleosides that are joined by intemucleoside linkages that do not have phosphoms atoms. Intemucleoside linkages of this type include short chain alkyl, cycloalkyl, mixed heteroatom alkyl, mixed heteroatom cycloalkyl, one or more short chain heteroatomic and one or more short chain heterocyclic. These intemucleoside linkages include, but are not limited to, siloxane, sulfide, sulfoxide, sulfone, acetyl, formacetyl, thioformacetyl, methylene formacetyl, thioformacetyl, alkeneyl, sulfamate, methyleneimino, methylenehydrazino, sulfonate, sulfonamide, amide and others having mixed N, O, S and CH2 component parts. Representative U.S. patents that teach the preparation of the above oligonucleosides include, but are not limited to, U.S.: 5,034,506; 5,166,315; 5,185,444; 5,214,134; 5,216,141; 5,235,033; 5,264,562; 5,264,564; 5,405,938; 5,434,257; 5,466,677; 5,470,967; 5,489,677; 5,541,307; 5,561,225; 5,596,086; 5,602,240; 5,610,289; 5,602,240; 5,608,046; 5,610,289; 5,618,704; 5,623,070; 5,663,312; 5,633,360; 5,677,437; 5,792,608; 5,646,269 and 5,677,439, certain of which are commonly owned with this application, and each of which is herein i incorporated by reference. The term "nucleobase" or "heterocyclic base moiety" as used herein, is intended to by synonymous with "nucleic aC1d base or mimetic thereof." In general, a nucleobase is any substructure that contains one or more atoms or groups of atoms capable of hydrogen bonding to a base of a nucleic aC1d. I As used herein, "unmodified" or "natural" nucleobases include the purine bases adenine (A) and guanine (G), and the pyrimidine bases thymine (T), cytosine (C) and uraC1l (U). Modified nucleobases include other synthetic and natural nucleobases such as 5-methylcytosine (5-me-C), 5-hydroxymethyl cytosine, xanthine, hypoxanthine, 2-aminoadenine, 6-methyl and other alkyl derivatives of adenine and guanine, 2-propyl and other alkyl derivatives of adenine and guanine, 2-thiouraC1l, 2-thiothymine and 2-thiocytosine, 5-halouraC1l and cytosine, 5-propynyl (-C^C-CHs) uraC1l and cytosine and other alkynyl derivatives of pyrimidine bases, 6-azo uraC1l, cytosine and thymine, 5-uraC1l (pseudouraC1l), 4-thiouraC1l, 8-halo, 8-amino, 8-thiol, 8-thioalkyl, 8-hydroxyl and other 8-substituted adenines and guanines, 5-halo particularly 5-bromo, 5-trifluoromethyl and other 5-substituted uraC1ls and cytosines, 7-methylguanine and 7-methyladenine, 2-F-adenine, 2-amino-adenine, 8-azaguanine and 8-azaadenine, 7-deazaguanine and 7-deazaadenine, 3-deazaguanine and 3-deazaademne, universal bases, hydrophobic bases, promiscuous bases, size-expanded bases, and fluorinated bases as defined herein. Further modified nucleobases include tricyclic pyrimidines such as phenoxazine cytidine(lH-pyrimido[5,4-b][l,4]benzoxazin-2(3H)-one), phenothiazine cytidine (lH-pyriinido[5,4-b][l ,4]benzothiazin-2(3H)-one), G-clamps such as a substituted phenoxazine cytidine (e.g. 9-(2-aminoethoxy)-H-pyrimido[5,4-b][l,4]benzoxazin-2(3H)-one), carbazole cytidine (2H-pyrimido[4,5-b]indol-2-one), pyridoindole cytidine (H-pyrido[3',2':4,5]pyrrolo[2,3-d]pyrimidin-2-one). Modified nucleobases may also include those in which the purine or pyrimidine base is replaced with other heterocycles, for example 7-deaza-adenine, 7-deazaguanosine, 2-aminopyridine and 2-pyridone. Further nucleobases include those disclosed in United States Patent No. 3,687,808, those disclosed in The ConC1se Encyclopedia Of Polymer SC1enC6And Engineering, pages 858-859, Kroschwitz, J.L, ed. John Wiley & Sons, 1990, those disclosed by Englisch et al, Angewandte Chemie, International Edition, 1991, 30,613, and those disclosed by Sanghvi, Y.S., Chapter 15, Antisense Research and Applications, pages 289-302, Crooke, S.T. and Lebleu, B., ed., CRC Press, 1993. Modified nucleobases include, but are not limited to, universal bases, hydrophobic bases, promiscuous bases, size-expanded bases, and fluorinated bases as defined herein. Certain of these nucleobases are particularly useful for increasing the binding affinity of the oligomeric compounds of the invention. These include 5-substituted pyrimidines, 6-azapyrimidines and N-2, N-6 and 0-6 substituted purines, including 2-aminopropyladenine, 5-propynyluraC1l and 5-propynylcytosine. S-methylC1^osine substitutions have been shown to increase nucleic aC1d duplex stability by 0.6-1.2 °C (Sanghvi, Y.S., Crooke, S.T. and Lebleu, B., eds., Antisense Research and Applications, CRC Press, Boca Raton, 1993, pp. 276-278) and are presently preferred base substitutions, even more particularly when combined with 2'-0-methoxyethyl sugar modifications. Representative United States patents that teach the preparation of certain of the above noted modified nucleobases as well as other modified nucleobases include, but are not limited to, the above noted U.S. 3,687,808, as well as U.S.: 4,845,205; 5,130,302; 5,134,066; 5,175,273; 5,367,066; 5,432,272; 5,457,187; 5,459,255; 5,484,908; 5,502,177; 5,525,711; 5,552,540; 5,587,469; 5,594,121; 5,596,091; 5,614,617; 5,645,985; 5,830,653; 5,763,588; 6,005,096; and 5,681,941, certain of which are commonly owned with the instant appUcation, and each of which is herein incorporated by reference, and United States patent 5,750,692, which is commonly owned with the instant application and also herein incorporated by reference. OUgomeric compounds of the present invention may also contain one or more nucleosides having modified sugar moieties. The furanosyl sugar ring can be modified in a number of ways including substitution with a substituent group, bridging to form a BNA and substitution of the 4-0 with a heteroatom such as S or N(R). Some representative U.S. patents that teach the preparation of such modified sugars include, but are not limited to, U.S.: 4,981,957; 5,118,800; 5,319,080; 5,359,044; 5,393,878; 5,446,137; 5,466,786; 5,514,785; 5,519,134; 5,567,811; 5,576,427; 5,591,722; 5,597,909; 5,610,300; 5,627,053; 5,639,873; 5,646,265; 5,658,873; 5,670,633; 5,792,747; 5,700,920; 6,600,032 and International Application PCT/US2005/019219, filed June 2, 2005 and published as WO 2005/121371 on December 22, 2005 certain of which are commonly owned with the instant application, and each of which is herein incorporated by referenC6in its entirety. A representative list of preferred modified sugars includes but is not limited to substituted sugars having a 2'-F, 2'-OCH2 or a 2'-0(CH2)2-OCH3 substituent group; 4'-thio modified sugars and bicyclic modified sugars. As used herein the term "nucleoside mimetic" is intended to include those structures used to replaC6the sugar or the sugar and the base not the linkage at one or more positions of an oligomeric compound such as for example nucleoside mimetiC6 having morpholino or bicyclo[3.1 .OJhexyl sugar mimetiC6 e.g. non furanose sugar units with a phosphodiester linkage. ■> The term "sugar surrogate" overlaps with the slightly broader term "nucleoside mimetic" but is intended to indicate replacement of the sugar unit (furanose ring) only. The term "nucleotide mimetic" is intended to include those structures used to replaC6the nucleoside and the linkage at one or more positions of an oligomeric compound such as for example peptide nucleic aC1ds or morpholinos (morpholinos linked by -N(H)-C(=0)-0- or other non-phosphodiester linkage). ) The oligomeric compounds in accordanC6with the present invention can comprise from about 8 to about 80 nucleosides and/or modified nucleosides or mimetiC6 in length. One of ordinary skill in the art will appreC1ate that the invention embodies oligomeric compounds of 8, 9,10, 11, 12,13,14,15, 16,17,18,19, 20,21,22,23,24, 25, 26,27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39,40, 41,42, 43,44,45, 46, 47,48,49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, ' In another embodiment, the oligomeric compounds of the invention are 8 to 40 nucleosides and/or modified nucleosides or mimetiC6 in length. One having ordinary skill in the art will appreC1ate that this embodies oligomeric compounds of 8, 9,10,11,12, 13, 14, 15, 16, I 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39 or 40 nucleosides and/or modified nucleosides or mimetiC6 in length, or any range therewithin. In another embodiment, the oligomeric compoimds of the invention are 8 to 20 nucleosides and/or modified nucleosides or mimetiC6 in length. One having ordinary skill in the art will appreC1ate that this embodies oligomeric compounds of 8, 9,10,11,12,13, 14,15,16, 17,18,19 or 20 nucleosides and/or modified nucleosides or mimetiC6 in length, or any range therewithin. In another embodiment, the oligomeric compounds of the invention are 10 to 16 nucleosides and/or modified nucleosides or mimetiC6 in length. One having ordinary skill in the art will appreC1ate that this embodies oligomeric compounds of 10,11,12,13, 14,15 or 16 nucleosides and/or modified nucleosides or mimetiC6 in length, or any range therewithin. In another embodiment, the oligomeric compounds of the invention are 10 to 14 nucleosides and/or modified nucleosides or mimetiC6 in length. One having ordinary skill in the art will appreC1ate that this embodies oligomeric compounds of 10,11,12,13 or 14 nucleosides and/or modified nucleosides or mimetiC6 in length, or any range therewithin. Chimeric oligomeric compounds have differentially modified nucleosides at two or more positions and are generally defined as having a motif. Chimeric oligomeric compounds of the invention may be formed as composite structures of two or more oligonucleotides, oligonucleotide analogs, oligonucleosides and/or oligonucleotide mimetiC6 as described above. Representative U.S. patents that teach the preparation of such hybrid structures include, but are not limited to, U.S.: 5,013,830; 5,149,797; 5,220,007; 5,256,775; 5,366,878; 5,403,711; 5,491,133; 5,565,350; 5,623,065; 5,652,355; 5,652,356; and 5,700,922, certain of which are commonly owned with the instant application, and each of which is herein incorporated by referenC6in its entirety. Oligomerization of modified and unmodified nucleosides and mimetiC6 therof, in one aspect of the present invention, is performed according to literature procedures for DNA (Protocols for Oligonucleotides and Analogs, Ed. Agrawal (1993), Humana Press) and/or RNA (Scaringe, Methods (2001), 23, 206-217; Gait et al., Applications of Chemically synthesized RNA in RNA:Protein Interactions, Ed. Smith (1998), 1-36; Gallo et al., Tetrahedron (2001), 57, 5707-5713) synthesis as appropriate. Additional methods for solid-phase synthesis may be found m Caruthers U.S. PatentsNos. 4,415,732; 4,458,066; 4,500,707; 4,668,777; 4,973,679; and 5,132,418; and Koster U.S. Patents Nos. 4,725,677 and Re. 34,069. CommerC1ally available equipment routinely used for the support medium based synthesis of oligomeric compounds and related compounds is sold by several vendors including, for example. Applied Biosystems (Foster C1ty, CA). Any other means for such synthesis known in the art may additionally or alternatively be employed. Suitable solid phase techniques, including automated synthesis techniques, are described in F. Eckstein (ed.), Oligonucleotides and Analogues, a Practical Approach, Oxford University Press, New York (1991). The synthesis of RNA and related analogs relative to the synthesis of DNA and related analogs has been increasing as efforts in RNAi increase. The primary RNA synthesis strategies that are presently being used commerC1ally include 5'-0-DMT-2'-0-t-butyldimethylsilyl (TBDMS), 5'-0-DMT-2'-0-[ 1 (2-fluorophenyl)-4-methoxypiperidin-4-yl] (FPMP), 2'-0-[(triisopropylsilyl)oxy]methyl (2'-0-CH2-0-Si(iPr)3 (TOM), and the 5'-0-silyl ether-2'-AC6(5'-0-bis(trimethylsiloxy)cyclododecyloxysilyl ether (DOD)-2'-0-bis(2-acetoxyethoxy)methyl (ACE). A current list of some of the major companies currently offering RNA products include PierC6Nucleic AC1d Technologies, Dharmacon Research Inc., Ameri Biotechnologies Inc., and Integrated DNA Technologies, Inc. One company, Princeton Separations, is marketing an RNA synthesis activator advertised to reduC6couplingT1mes espeC1ally with TOM and TBDMS chemistries. Such an activator would also be amenable to the present invention. The primary groups being used for commerC1al RNA synthesis are: TBDMS = 5'-0-DMT-2'-0-t-butyldimethylsilyl; TOM = 2'-0-[(triisopropylsilyl)oxy]methyl; DOD/AC6 = (5'-0-bis(trimeihyIsiloxy)cyclododecyloxysilyl ether-2'-0-bis(2-acetoxyethoxy)methyl FPMP =5'-0-DMT-2'-0-[l(2-fluorophenyl)-4-methoxypiperidin-4-yl]. All of the aforementioned RNA synthesis strategies are amenable to the present invention. Strategies that would be a hybrid of the above e.g. using a 5'-protecting group from one strategy with a 2'-0-protecting from another strategy is also amenable to the present invention. hi the context of this invention, "hybridization" means the pairing of complementary sfrands of oligomeric compounds. In the present invention, one mechanism of pairing involves hydrogen bonding, which may be Watson-Crick, Hoogsteen or reversed Hoogsteen hydrogen bonding, between complementary nucleoside or nucleotide bases (nucleobases) of the sfrands of ' oligomeric compounds. For example, adenine and thymine are complementary nucleobases which pair through the formation of hydrogen bonds. Hybridization can occur imder varying C1rcumstances. An oligomeric compound is speC1fically hybridizable when binding of the compound to the target nucleic aC1d interferes with the normal ftinction of the target nucleic aC1d to cause a I loss of activity, and there is a suffiC1ent degree of complementarity to avoid non-speC1fic binding of the oligomeric compound to non-target nucleic aC1d sequences under conditions in which speC1fic binding is desired, i.e., under physiological conditions in the case of m vivo assays or therapeutic treatment, and under conditions in which assays are performed in the case of in vitro assays. "Complementary," as used herein, refers to the capaC1ty for preC1se pairing of two nucleobases regardless of where the two are located. For example, if a nucleobase at a certain position of an oligomeric compound is capable of hydrogen bonding with a nucleobase at a certain position of a target nucleic aC1d, the target nucleic aC1d being a DNA, RNA, or oUgonucleotide molecule, then the position of hydrogen bonding between the oligonucleotide and the target nucleic aC1d is considered to be a complementary position. The oHgomeric compound and the further DNA, RNA, or oligonucleotide molecule are complementary to each other when a suffiC1ent number of complementary positions in each molecule are occupied by nucleobases which can hydrogen bond with each other. Thus, "speC1fically hybridizable" and "complementary" are terms which are used to indicate a suffiC1ent degree of preC1se pairing or complementarity over a suffiC1ent number of nucleobases such that stable and speC1fic binding occurs between the oligonucleotide and a target nucleic aC1d. It is understood in the art that the sequenC6of an oligomeric compound need not be 100% complementary to that of its target nucleic aC1d to be speC1fically hybridizable. Moreover, an oligonucleotide may hybridize over one or more segments such that intervening or adjacent segments are not involved in the hybridization event (e.g., a loop structure or hairpin structure). The oligomeric compounds of the present invention can comprise at least about 70%, at least about 80%, at least about 90%, at least about 95%, or at least about 99% sequenC6complementarity to a target region within the target nucleic aC1d sequenC6to which they are targeted. For example, an oligomeric compound in which 18 of 20 nucleobases of the oligomeric compound are complementary to a target region, and would therefore speC1fically hybridize, would represent 90 percent complementarity. In this example, the remaining noncomplementary nucleobases may be clustered or interspersed with complementary nucleobases and need not be contiguous to each other or to complementary nucleobases. As such, an oligomeric compound which is 18 nucleobases in length having 4 (four) noncomplementary nucleobases which are flanked by two regions of complete complementarity with the target nucleic aC1d would have 77.8% overall complementarity with the target nucleic aC1d and would thus fall within the scope of the present invention. Percent complementarity of an oUgomeric compound with a region of a target nucleic aC1d can be determined routinely using BLAST programs (basic local alignment search tools) and PowerBLAST programs known in the art (Altschul et al., J. Mol. Biol., 1990,215,403-410; Zhang and Madden, Genome Res., 1997, 7, 649-656). Further included in the present invention are oligomeric compounds such as antisense oligomeric compounds, antisense oligonucleotides, ribozymes, external guide sequenC6(EGS) oligonucleotides, alternate splicers, primers, probes, and other oligomeric compounds which hybridize to at least a portion of the target nucleic aC1d. As such, these oligomeric compounds may be introduced in the form of single-stranded, double-stranded, C1rcular or hairpin oligomeric compoxmds and may contain structural elements such as internal or terminal bulges or loops. OnC6introduced to a system, the oUgomeric compounds of the invention may eliC1t the action of one or more enzymes or structural proteins to effect modification of the target nucleic aC1d. One non-limiting example of such an enzyme is RNAse H, a cellular endonuclease which cleaves the RNA strand of an RNA:DNA duplex. It is known in the art that single-stranded oligomeric compounds which are "DNA-like" eliC1t RNAse H. Activation of RNase H, therefore, resuhs in cleavage of the RNA target, thereby greatly enhanC1ng the effiC1ency of oligonucleotide-mediated inhibition of gene expression. Similar roles have been postulated for other ribonucleases such as those in the RNase III and ribonuclease L family of enzymes. While one form of oligomeric compound is a single-stranded antisense oligonucleotide, in many speC1es the introduction of double-stranded structures, such as double-stranded RNA (dsRNA) molecules, has been shown to induC6potent and speC1fic antisense-mediated reduction of the function of a gene or its assoC1ated gene products. This phenomenon occurs in both plants and animals and is believed to have an evolutionary connection to viral defense and transposon silenC1ng. In some embodiments, "suitable target segments" may be employed in a screen for additional oligomeric compoimds that modulate the expression of a selected protein. "Modulators" are those oHgomeric compounds that decrease or increase the expression of a nucleic aC1d molecule encoding a protein and which comprise at least an 8-nucleobase portion which is complementary to a suitable target segment. The screening method comprises the steps of contacting a suitable target segment of a nucleic aC1d molecule encoding a protein with one or more candidate modulators, and selecting for one or more candidate modulators which decrease or increase the expression of a nucleic aC1d molecule encoding a protein. OnC6it is shown that the candidate modulator or modulators are capable of modulating (e.g. either decreasing or increasing) the expression of a nucleic aC1d molecule encoding a peptide, the modulator may then be employed in further investigative studies of the function of the peptide, or for use as a research, diagnostic, or therapeutic agent in accordanC6with the present invention. The suitable target segments of the present invention may also be combined with their respective complementary antisense oligomeric compounds of the present invention to form stabiUzed double-stranded (duplexed) oHgonucleotides. Such double stranded oligonucleotide moieties have been shown in the art to modulate target expression and regulate translation as well as RNA processsing via an antisense mechanism. Moreover, the double-stranded moieties may be subject to chemical modifications (Fire et al.. Nature, 1998, 391, 806-811;T1mmons and Fire, Nature 1998, 395, 854;T1mmons et al.. Gene, 2001, 263, 103-112; Tabara et al., SC1ence, 1998, 282,430-431; Montgomery et al., Proc. Natl. Acad. SC1. USA, 1998, 95,15502-15507; Tuschl et al.. Genes Dev., 1999,13, 3191-3197; Elbashir et al., Nature, 2001, 411, 494-498; ' Elbashir et al., Genes Dev. 2001,15,188-200). For example, such double-stranded moieties have been shown to inhibit the target by the classical hybridization of antisense strand of the duplex to the target, thereby triggering enzymatic degradation of the target (Tijsterman et al., SC1ence, 2002, 295, 694-697). . The oligomeric compounds of the present invention can also be applied in the areas of drug discovery and target vaHdation. The present invention comprehends the use of the ohgomeric compoimds and targets identified herein in drug discovery efforts to eluC1date relationships that exist between proteins and a disease state, phenotype, or condition. These methods include detecting or modulating a target peptide comprising contacting a sample,T1ssue, cell, or organism with the oligomeric compounds of the present invention, measuring the nucleic aC1d or protein level of the target and/or a related phenotypic or chemical endpoint at someT1me after treatment, and optionally comparing the measured value to a non-treated sample or sample treated with a further oligomeric compound of the invention. These methods can also be performed in parallel or in combination with other experiments to determine the function of unknown genes for the process of target validation or to determine the validity of a particular gene product as a target for treatment or prevention of a particular disease, condition, or phenotype. Effect of nucleoside modifications on RNAi activity is evaluated according to existing literature (Elbashir et al., Nature (2001), 411,494-498; Nishikura et al., Cell (2001), 107,415-416; and Bass et al.. Cell (2000), 101,235-238.) The ohgomeric compounds of the present invention can be utilized for diagnostiC6, therapeutiC6, prophylaxis and as research reagents and kits. Furthermore, antisense oligonucleotides, which are able to inhibit gene expression with exquisite speC1fiC1ty, are often used by those of ordinary skill to eluC1date the fiinction of particular genes or to distinguish between fimctions of various members of a biological pathway. For use in kits and diagnostiC6, the oligomeric compounds of the present invention, either alone or in combination with other oligomeric compounds or therapeutiC6, can be used as tools in differential and/or combinatorial analyses to eluC1date expression patterns of a portion or the entirecomplement of genes expressed within cells andT1ssues. As one nonlimiting example, expression patterns within cells orT1ssues treated with one or more oligomeric compounds are compared to control cells orT1ssues not treated with oligomeric compounds and the patterns produced are analyzed for differential levels of gene expression as they pertain, for example, to disease assoC1ation, signaling pathway, cellular localization, expression level, size, structure or function of the genes examined. These analyses can be performed on stimulated or unstimulated cells and in the presenC6or absenC6of other compounds and or oligomeric compounds which affect expression patterns. Examples of methods of gene expression analysis known in the art include DNA arrays or microarrays (Brazma and Vilo, FEBS Lett., 2000, 480,17-24; Cells, et al, FEES Lett., 2000, 480, 2-16), SAGE (serial analysis of gene expression)(Madden, et al., Drug Discov. Today, 2000, 5,415-425), READS (restriction enzyme amplification of digested cDNAs) (Prashar and Weissman, Methods Enzymol., 1999, 303, 258-72), TOGA (total gene expression analysis) (Sutcliffe, et al, Proc. Natl. Acad. Sci. U. S. A., 2000,97,1976-81), protein arrays and proteomics (Cells, et al., FEBS Lett., 2000,480,2-16; Jungblut, et al., Electrophoresis, 1999,20, 2100-10), expressed sequence tag (EST) sequencing (Celis, et al, FEBS Lett., 2000, 480, 2-16; Larsson, et al., J. BiotechnoL, 2000, 80, 143-57), subtractive RNA fingerprinting (SuRF) (Fuchs, et al.. Anal. Biochem., 2000,286, 91-98; Larson, et al.. Cytometry, 2000, 41, 203-208), subtractive cloning, differential display (DD) (Jurecic and Belmont, Ctorr. Opin. Microbiol., 2000, 3, 316-21), comparative genomic hybridization (CaruUi, et al., J. Cell Biochem. Suppl., 1998, 31,286-96), FISH (fluorescent in situ hybridization) techniques (Going and Gusterson, Eur. J. Cancer, 1999, 35,1895-904) and mass spectrometry methods (To, Comb. Chem. High Throughput Screen, 2000, 3, 235-41). The oligomeric compounds of the invention are useful for research and diagnostics, because these oligomeric compounds hybridize to nucleic acids encoding proteins. For example, oligonucleotides that are shown to hybridize with such efficiency and under such conditions as disclosed herein as to be effective protein inhibitors will also be effective primers or probes under conditions favoring gene amplification or detection, respectively. These primers and probes are useful in methods requiring the specific detection of nucleic acid molecules encoding proteins and in the amplification of the nucleic acid molecules for detection or for use in further studies. Hybridization of the antisense oligonucleotides, particularly the primers and probes, of the invention with a nucleic acid can be detected by means known in the art. Such means may include conjugation of an enzyme to the oligonucleotide, radiolabelling of the oligonucleotide or any other suitable detection means. Kits using such detection means for detecting the level of selected proteins in a sample may also be prepared. While the present invention has been described with specificity in accordance with certain of its embodiments, the following examples serve only to illustrate the invention and are not intended to limit the same. 1), triethylamine (11.44 mL, 81.5 mmol) and 4-dimethylaminoethylpyridine (0.47 g, 3.9 mmol) in CH2C12 (184 mL). After the addition was complete, the reaction was gradually warmed to rt and stirred for an additional 16h. The reaction was diluted with CH2C12 and sequentially washed with 5% aqueous HCl, saturated NaHCOs, brine, dried (Na2S04) and concentrated under ' EtOAc/hexanes) provided alcohol 3 (11.53g, 59%) and alcohol 4 (3.93 g, 22%) as white solids. B) Alcohol (6) Dimethylsulfoxide (3.36 mL, 47.5 mmol) was added dropwise to a cold (-78°C) solution I ofoxalyl chloride (2.08 mL, 23.7 mmol) in CH2C12 (130 mL). After stirring for 30 min, a solution of alcohol 3 (6.7 g, 15.8 mmol) in CH2C12 (20 mL) was added to the reaction. The stirring was continued for 45 min at -78°C and triethylamine (10.0 mL, 71.2 mmol) was added to the reaction. The reaction was stirred at -78°C for 15 min after which the iC6bath was removed and the reaction was allowed to gradually warm over 45 min. The reaction was then poured into CH2C12 and the organic phase was sequentially washed with 5% aqueous HCl, saturated NaHCOs, brine, dried (Na2S04) and concentrated under vacuum to provide aldehyde 5, which was used without any ftirther purification. A suspension of cerium III chloride (5.84 g, 23.7 mmol) in THF (130 mL) was stirred at rt for 90 min. The reaction was cooled in an iC6bath and methyl magnesium bromide (17.0 mL of a IM solution in THF) was added over 5 min and the stirring continued for another 90 min. A solution of crude aldehyde 5 (fi'om above) in THF (20 mL) was added to the reaction. After stirring for another 90 min, the reaction was quenched with sat NH4C1 solution and poured into EtOAc. The organic layer was sequentially washed with 5% aqueous HCl, saturated NaHCOs, brine, dried (Na2S04) and concentrated under vacuum. Purification by column chromatography (Si02, eluting with 15% EtOAc/hexanes) provided alcohol 6 (5.52 g, 80% fi-om 3). C) Mesylate (7) Methanesulfonyl chloride (0.55 mL, 7.0 mmol) was added to a cold (0°C) solution of alcohol 6 (2.77 g, 6.4 mmol), triethylamine (1.1 mL, 7.7 mmol) and 4-dimethylaminopyridine (84 mg, 0.7 mmol) in CH2C12 (14 mL). After stirring at rt for Ih, the reaction was poured into CHC13 and the organic layer was sequentially washed with 5% aqueous HCl, saturated NaHCOs, brine, dried (Na2S04) and concentrated under vacuum. Purification by column chromatography (Si02, eluting with 15% EtOAc/hexanes) provided mesylate 7 (2.97 g, 91 %). D) Triacetate (8) Concentrated H2SO4 (3 drops) was added to a solution of mesylate 7 (2.97 g, 5.8 mmol) in glaC1al acetic aC1d (29 mL) and acetic anhydride (5.8 mL). After stirring at rt for Ih, the reaction was poured into EtOAc and the organic layer was washed with water, saturated NaHCOs, brine, dried (Na2S04) and concentrated under vacuum. Purification by column chromatography (SiOa, eluting with 33% to 50% EtOAc/hexanes) provided triacetate 8 (2.48 g, 88%). 'HNMR(C6Cl3, P anomer): 5 7.39-7.30 (m, 5H), 6.23 (s, IH), 5.37 (d, IH), 5.19 (q, IH), 4.62 (d, IH), 4.52 (d, IH), 4.38 (s, IH), 4.34 (d, IH), 3.98 (d, IH), 2.91 (s, 3H), 2.12 (s, 3H), 2.08 (s, 3H), 2.06 (s, 3H), 1.55 (d, 3H). LCMS: retentionT1me 1.35 min; M+23 calC6. 511.1, found 511.0. E) Nucleoside (11) 7V,C>-Bis(trimethylsilyl)acetamide (4.9 mL, 20.0 mmol) was added to a suspension of triacetate 8 (2.47 g, 5.0 mmol) and uraC1l (0.70 g, 6.3 mmol) in CH3CN (15 mL). After heating at 40°C for 15 min to get a clear solution, trimethylsilyl triflate (1.18 mL, 6.5 mmol) was added to the reaction. After refluxing for 2h, the reaction was cooled to rt and poured into EtOAc. The organic layer was washed with saturated NaHCOs, brine, dried (Na2S04) and concentrated under vacuum to provide crude nucleoside 9, which was used without any purification. K2CO3 (2.07 g, 15 mmol) was added to a solution of nucleoside 9 (fi-om above) in MeOH (50 mL). After stirring for 16h at rt, the solvent was removed under vacuum and the residue was partitioned between 25% pyridine/EtOAc and brine. The organic phase was collected, dried (Na2S04) and concentrated under vacuum to provide 10, which was used without any fiirther purification. 'H NMR (MeOD): 6 7.74 (d, 2H), 7.29-7.14 (m, 5H), 5.53 (d, IH), 5.38 (s, IH), 4.48 (s, 2H), 4.18 (s, IH), 4.14 (sm, IH), 3.92 (s, IH), 3.66 (s, 2H), 1.08 (d, 3H). LCMS: retentionT1me 2.40 min; M-l-H calC6. 360.1, foimd 361.0. rer^Butyldiphenylsilyl chloride (1.73 mL, 6.7 mmol) was added to a cold (0°C) solution of nucleoside 10 (from above), triethylamine (1.4 mL, 10.0 mmol) and 4-dimethylaminopyridine (80 mg, 0.7 mmol) in CH2C12 (9 mL). After stirring for 16h at rt, the reaction was poured into EtOAc and the organic phase was sequentially washed with 5% aqueous HCl, saturated NaHCOa, dried (Na2S04) and concentrated under vacuum. Purification by column chromatography (SiOa, eluting with 50% EtOAc/hexanes) provided nucleoside 11 (2.02 g, 79% from 8) as a white solid. F) Nucleoside (12) Boron trichloride (16.7 mL of a IM solution in CH2C12) was carefully added to a cold (-15°C) solution of nucleoside 11 (2.0 g, 3.3 mmol) in CH2C12 (40 mL). After stirring at -1 S'^C for Ih, the reaction was cooled to -78°C and carefully quenched by the addition of MeOH/CH2Cl2 (1:1,10 mL). After stirring for an additional 10 min, the reaction was poured into CH2C12 and ) the organic phase was sequentially washed with 5% aqueous HCl, saturated NaHCOs, brine, dried (Na2S04) and concentrated under vacuum. Purification by column chromatography (Si02, eluting with 50% to 80% EtOAc/hexanes) provided nucleoside 12 as a white solid (1.02 g, 60%). ) G) Nucleoside (13) Triethylamine trihydrofluoride (2.98 mL, 18.3 mmol) was added to a solution of nucleoside 12 (1.86 g, 3.7 mmol) and triethylamine (1.03 mL, 7.3 mmol) in THF (36 mL), in a polypropylene tube. After stirring at rt for 16h, the reaction was concentrated under vacuum and the residue dissolved in EtOAc. The organic layer was sequentially washed with water, i saturated NaHCOs, brine, dried (Na2S04) and concentrated under vacuum. Purification by column chromatography (Si02,15% MeOH/CHCls) provided nucleoside 13 (1.31 g, product contaminated with triethylamine) as a white solid. H) Nucleoside (14) I 4,4'-Dimethoxytrityl chloride (DMTCl) (1.23 g, 3.7 mmol) was added to a solution of nucleoside 13 (fi-om above) in pyridine (18 mL). After stirring for 16 h at rt, additional DMTCl (0.12 g) was added to the reaction and the stirring was continued for another 8h. The reaction was then poured into EtOAc and the organic layer was sequentially extracted with brine, dried (Na2S04) and concentrated. Purification by column chromatography (Si02, eluting with 15% acetone/CHCls) provided nucleoside 14 (1.85 g, 89%) as a white foam. 'H NMR (C6C13): 6 8.03 (d, IH), 7.44-2.28 (m, 14H), 6.86 (d, 4H), 5.63 (d, IH), 5.60 (s, IH), 4.32 (m, IH), 4.13 (s, IH), 3.81 (s, 6H), 3.49 (d, IH), 3.37 (d, IH), 1.18 (d, 3H). I) Preparation of the phosphoramidite, (15',3J?,4i?,6J?,75)-7-[2-cyanoethoxy-(diisopropylamino)phosphiii oxy]-l-(4,4'-dimethoxytrityloxymetliyl)-3-(uraC1l-l-yl)-6-methyI-2,5-dioxa-bicyclo[2.2.1]heptane (15) 2-Cyanoethyl tetraisopropylphorodiamidite (0.69 mL, 2.2 mmol) was added to a solution of nucleoside 14 (0.83 g, 1.4 mmol), tetrazole (80 mg, 1.2 mmol) and A^-methylimidazole (29 ).iL, 0.36 nunol) in DMF (7.2 mL). After stirring at rt for 8h, the reaction was poured into EtOAc and the organic layer was washed with 90% brine, brine, dried (Na2S04) and concentrated. The residue was dissolved in minimum amount of EtOAc and this solution was added to hexanes. The resulting precipitate was collected and further purified by column chromatography (Si02, eluting with 66% to 75% EtOAc/hexanes) to provide phosphoramidite 15 as a white solid (1.04 g, 94%). ^'P NMR (CDCI3) 5: 149.21,149.79. A) Nucleoside (16) ter^Butyldimethylsilyl chloride (0.79 g, 5.2 ramol) was added to a solution of nucleoside 14 (1.0 g, 1.7 mmol) and imidazole (0.70g, 10.4 mmol) in DMF (3.5 mL). After stirring at rt for 16h, the reaction was poured into EtOAc and the organic phase was sequentially extracted with brine, dried (Na2S04) and concentrated under vacuum. Purification by column chromatpography (Si02, eluting with 50% EtOAc/hexanes) provided nucleoside 16 (1.17 g, 99%o) as a white solid. B) Nucleoside (19) Phosphoras oxychloride (1.27 mL, 13.6 mmol) was added to a cold (0°C) suspension of 1,2,4-triazole (4.0 g, 58.0 mmol) in CH3CN (21 mL). After stirring for 15 min, triethylamine (9.57 mL, 68 mmol) was added to the reaction and the stirring continued for 30 min. A solution of nucleoside 16 (1.17g, 1.7 mmol) in CH3CN (10 mL) was added to the reaction at 0°C. After stirring for 10 min, the iC6bath was removed and the reaction was stirred at rt for 4h. The solvent was then removed under vacuum and the residue was partitioned between EtOAc and water. The organic layer was then washed with saturated NaHCOa, brine, dried (Na2S04) and concentrated under vacuum to provide crude 17, which was used without any further purification. Aqueous ammonia (4 mL) was added to a solution of nucleoside 17 (firom above) in dioxane (20 mL). After stirring at rt for 16h, the reaction was concentrated under vacuum and dried over high vacuum for 8h to provide nucleoside 18, which was used without any further purification. Benzoic anhydride (0.65 g, 2.9 mmol) was added to a solution of nucleoside 18 (firom above) in DMF (3 mL). After stirring at rt for 16h, the reaction was poured into EtOAc and the organic layer was extracted with saturated NaHCOs, brine, dried (Na2S04) and concentrated under vacuum. Purification by column chromatography (SiOi, eluting with 50% EtOAc/hexanes) provided nucleoside 19 (1.2 g, 90% fi-om 16) as a white solid. C) Nucleoside (20) Triethylamine trihydrofluoride (1.48 mL, 9.1 mmol) was added to a solution of nucleoside 19 (1.86 g, 3.7 mmol) and triethylamine (1.03 mL, 7.3 mmol) in THF (15 mL) a polypropylene tube. After stirring at rt for 16h, the reaction was concentrated under vacuum and the residue was dissolved in EtOAc and the organic layer was sequentially washed with water, saturated NaHCOs, brine, dried (Na2S04) and concentrated under vacuum. Purification by column chromatography (Si02, eluting with 5% MeOH/CHCla) provided nucleoside 20 (0.91 g, 90%) as a white solid. ^H NMR (MeOD) 5: 8.62 (d, IH), 8.02 (d. IH), 7.63 (m, 6H), 7.38 (m, 7H), 6.96 (d, 4H), 6.65 s, IH), 4.49 (s, IH), 4.36 (s, IH), 4.25 (m, IH), 3.53 (d, IH), 3.41 (d, IH), 1.18(d,3H). D) (15',3jR,4i?,6iZ,7iS)-7-[2-Cyaiioethoxy(diisopropylamino)phosphinoxy]-l-(4,4'- dimethoxytrityloxymethyl)-3-(4-iV-beiizoylcytosiii-l-yI)-6-methyl-2,5-dioxa-bicyclo- [2.2.1]lieptane (21) 2-Cyanoethyl tetraisopropylphorodiamidite (0.63 mL, 2.0 mmol) was added to a solution of nucleoside 20 (0.89 g, 1.3 mmol), tetrazole (73 mg, 1.1 mmol) and A'-methylimidazole (26 fxL, 0.33 mmol) in DMF (6.6 mL). After stirring at rt for 8h, the reaction was poured into EtOAc and the organic layer was washed with 90% brine, brine, dried (Na2S04) and concentrated. The residue was dissolved in minimum amount of EtOAc and this solution was added to hexanes. The resulting preC1pitate was collected and further purified by column chromatography (Si02, eluting with 75% to 90%) EtOAc/hexanes) to provide phosphoramidite 21 as a white solid (1.1 g, 95%). ^^PNMR (C6C13) 8:149.34,149.77. Example 3 Preparation of uridiiie-6-(5)-methyi BNA phosphoramidite, (15',3J?,4i?,65',75)-7-[2- cyanoethoxy(diisopropyIaraino)phosphinoxy]-l-(4,4'-dimethoxytrityloxymethyl)-3-(uraC1l- l-yI)-6-methyl-2,5-dioxa-bicyclo[2.2.1]heptane(38) Sodium hydride (2.39 g, 59.8 mmol) was added carefully to a cold (0°C) solution of commerC1ally available 1,2:5,6-Di-O-isopropylidene-a-D-allofuranose 1 (12.0g, 46 mmol) in DMF (75 mL). After stirring for 20 minutes, napthyl bromide (11.12 g, 50.8 mmol) was added to the reaction and the stirring was continued for another 2h. The reaction was carefully quenched with H2O and then poured into EtOAc and the organic layer was washed with water, brine, dried and concentrated. Purification by column chromatography (Si02, 10% to 33% EtOAc/hexanes) provided alcohol 22 as a white solid (18.1 g, 98%). B) Diol (25) Alcohol 22 (18g, 46 mmol) was dissolved in glaC1al acetic aC1d (150 mL) and H2O (60 mL). The reaction was stirred at rt for 16h after which it was concentrated xmder vacuum. The residue was then dissolved in EtOAc and the organic layer was washed with saturated NaHCOs, brine, dried and concentrated to provide crude 23, which was used without any further purification. A solution of sodium periodate (48 mmol, 1 Og) in water (350 mL) was added to a solution of the crude diol 23 obtained above, in 1,4-dioxane (140 mL). After stirring at rt for 90 minutes, the reaction was extracted with EtOAc and the organic layer was further washed with water, brine, dried (Na2S04) and concentrated to provide aldehyde 24, which was used without any further purification. The crude aldehyde 24 fi-om above, was dissolved in a mixture of THF:H20 (1:1, 100 mL) and the reaction was cooled in an iC6bath. Formaldehyde (25 mL, 35%w/w) and IN NaOH (100 mL) were added to the reaction. After stirring at rt for 16h, formaldehyde (5 mL) was added to the reaction and the stirring was continued for an additional 32h. The reaction was then concentrated to dryness and the residue was partitioned between EtOAc and water. The layers were separated and the organic layer was washed with additional IN NaOH, water, brine, dried and concentrated to provide diol 25 (12.96 g, 80%, three steps) as a white solid. C) Alcohol (26) ter^Butyldiphenylsilyl chloride (0.75 mL, 2.9 mmol) was added to a cold (0°C) solution of diol 25 (1 g, 2.8 mmol) and triethylamine (0.45 mL, 3.2 mmol). After stirring at rt for 16h, the reaction was poured into EtOAc and sequentially washed with 5% HCl, saturated NaHCOs, brine, dried (Na2S04) and concentrated. Purification by column chromatography (Si02, eluting with 10% to 40% EtOAc/hexanes) provided alcohol 26 (1.02 g, 61 %) as an oil (0.42 g of the regioisomeric silyl protected diol was also isolated). D) Alcohol (28) Dimethylsulfoxide (1.6 mL, 22.4 nraiol) was added dropwise to a cold (-78°C) solution of oxalyl chloride (0.98 mL, 11.2 mmol) in CH2C12 (70 mL). After stirring for 30 min, a solution of alcohol 26 (4.8 g, 8.0 mmol) in CH2C12 (20 mL) was added to the reaction. The stirring was continued for 45 min at -78°C and triethylamine (4.72 mL, 33.7 mmol) was added to the reaction. The reaction was stirred at -78°C for 15 min after which the iC6bath was removed and the reaction was allowed to gradually warm over 45 min. The reaction was then poured into CH2C12 and the organic phase was sequentially washed with 5% aqueous HCl, saturated NaHCOs, brine, dried (Na2S04) and concentrated under vacuum to provide aldehyde 27, which was used without any further purification. A suspension of cerium III chloride (2.96 g, 12.0 mmol) in THF (50 mL) was stirred at rt for 90 min. The reaction was cooled in an iC6bath and methyl magnesium bromide (8.6 mL of a 1.4 M solution in THF, 12 mmol) was added over 5 min and the stirring continued for another 90 min after which the reaction was cooled to -78°C. A solution of crude aldehyde 27 (from above) in THF (20 mL) was added to the reaction. After stirring for another 90 min, the reaction was quenched with sat NH4C1 solution and poured into EtOAc. The organic layer was sequentially washed with 5% aqueous HCl, saturated NaHCOs, brine, dried (Na2S04) and concentrated under vacuum. Purification by column chromatography (Si02, eluting with 20% EtOAc/hexanes) provided alcohol 28 (4.37 g, 89% fi-om 26). E) Diacetate (32) Dimethylsulfoxide (1.41 mL, 19.9 mmol) was added dropwise to a cold (-78°C) solution of oxalyl chloride (0.87 mL, 10.0 mmol) in CH2C12 (70 mL). After stirring for 30 min, a solution of alcohol 28 (4.35 g, 7.1 mmol) in CH2C12 (20 mL) was added to the reaction. The stirring was continued for 45 min at -78°C and triethylamine (4.20 mL, 30.0 mmol) was added to the reaction. The reaction wais stirred at -78°C for 15 min after which the iC6bath was removed and the reaction was allowed to gradually warm over 45 min. The reaction was then poured into CH2C12 and the organic phase was sequentially washed with 5% aqueous HCl, saturated NaHCOs, brine, dried (Na2S04) and concentrated under vacuum to provide ketone 29, which was used without any fiirther purification. Diisobutyl aluminum hydride (13.7 mL of a IM solution in CH2C12,13.7 mmol) was added to a cold solution of ketone 29 (firom above) in CH2C12 (15 mL). After stirring for 2h at -78°C, the reaction was quenched by the addition of saturated NH4C1 and poured into CHC13. The organic layer was then sequentially washed with 5% aqueous HCl, saturated NaHCOs, brine, dried (Na2S04) and concentrated under vacuum to provide alcohol 30 which was used without any further purification. Methanesulfonyl chloride (0.11 mL, 1.4 mmol) was added to a cold (0°C) solution of alcohol 30 (from above), triethylamine (1.77 mL, 10.5 mmol) and 4-dimethylaminopyridine (85 mg, 0.7 mmol) in CH2C12 (21 mL). After stirring at rt for Ih, the reaction was poured into CHC13 and the organic layer was sequentially washed with 5% aqueous HCl, saturated NaHCOs, brine, dried (Na2S04) and concentrated under vacuum to provide mesylate 31, which was used without any purification. Concentrated H2SO4 (2 drops) was added to a solution of mesylate 31 (from above) in glaC1al acetic aC1d (15 mL) and acetic anhydride (3.0 mL). After stirring at rt for Ih, the reaction was poured into EtOAc and the organic layer was washed with water, saturated NaHCOs, brine, dried (Na2S04) and concentrated under vacuum. Purification by column chromatography (Si02, eluting with 20% to 33% EtOAc/hexanes) provided diacetate 32 (3.0 g, 58% from 28). F) Nucleoside (34) A^,0-Bis(trimethylsilyl)acetamide (3.45 mL, 14.0 mmol) was added to a suspension of diacetate 32 (3.0 g, 4.1 mmol) and uraC1l (0.57 g, 5.1 mmol) in CH3CN (20 mL). After heating at 40'C for 15 min to get a clear solution, trimethylsilyl triflate (0.95 mL, 5.3 mmol) was added to the reaction. After refluxing for 2h, the reaction was cooled to rt and poured into EtOAc. The organic layer was washed with saturated NaHCOs, brine, dried (Na2S04) and concentrated under vacuum to provide crude nucleoside 33, which was used vsdthout any purification. K2CO3 (1.66 g, 12.0 mmol) was added to a solution of nucleoside 33 (from above) in MeOH (40 mL). After stirring at rt for 16h, the reaction was concentrated under vacuum and the residue was dissolved in 25% pyridine/EtOAc and extracted with brine, dried (Na2S04) and concentrated under vacuum. Purification by column chromatography (Si02, eluting with 40% EtOAc/hexanes) provided nucleoside 34 (2.0 g, 76% from 32) as a white solid. G) Nucleoside (35) 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) (1.4 g, 6.2 mmol) was added to a solution of nucleoside 34 (2.0 g, 3.1 mmol) in dichloromethane (30 mL) and H2O (1.5 mL). After stirring for 3h at rt, additional DDQ (0.5 g) was added to the reaction. After stirring for another 10 minutes, the reaction was concentrated under vacuum and the residue was dissolved in EtOAc. The organic layer was then sequentially washed with water, water:saturated NaHCOs (1:1), brine, dried (Na2S04) and concentrated. Purification by column chromatography (Si02, 80% EtOAc/hexanes) provided nucleoside 35 (1.25 g, 80%) as a white solid. H) Nucleoside (36) Triethylamine trihydroflouride (2.4 mL, 14.7 mmol) was added to a solution of nucleoside 35 (1.25 g, 2.5 mmol) and triethlyamine (1.0 mL, 7.4 mmol) in THF (25 mL) in a polypropylene tube. After stirring at rt for 24h, the reaction was concentrated under vacuum and the residue was dissolved in EtOAc. The organic layer was then washed with water, saturated NaHCOs, brine, dried and concentrated (Na2S04). Purification by column chromatography (Si02, eluting with 5% to 10% MeOH/CHCla) provided nucleoside 36 (0.88 g) as a white solid (product contaminated with EtsN). I) Nucleoside (37) Dimethoxytrityl chloride (0.91 g, 2.7 mmol) was added to a solution of nucleoside 36 (from above) in pyridine (12 mL). After stirring at rt for 16h, the reaction was poured into EtOAc and the organic layer was washed with brine, dried and concentrated. Purification by column chromatography (Si02, eluting with 90% EtOAc/hexanes) provided nucleoside 37 (1.28 g, 86% from 36) as a white solid. J) (15',3if,4i?,6iS',75)-7-[2-Cyaiioetlioxy(diisopropyIamino)phosphiii oxy]-l-(4,4'-dimethoxytrityloxymethyl)-3-(uraC1I-l-yl)-6-methyl-255-dioxa-bicyclo[2.2.11heptane(38) 2-Cyanoethyl tetraisopropylphorodiamidite (0.46 mL, 1.5 mmol) was added to a solution of nucleoside 37 (0.59 g, 1,0 mmol), tetrazole (57 mg, 0.82 mmol) and AT-methylimidazole (20 j^L, 0.25 mmol) in DMF (5 mL). After stirring at rt for 8h, the reaction was poured into EtOAc and the organic layer was washed with 90% brine, brine, dried (Na2S04) and concentrated. Purification by column chromatography (Si02, eluting with 66% to75% EtOAc/hexanes) provided phosphoramidite 38 as a white solid (0.75 g, 97%). '^P NMR (C6C13) 5: 149.36, 149.53. Example 4 Preparation of A'-Bz-cytosiiie-6-(5)-methyl BNA phosphoramidite, 2.2 Preparation of (15',3^j4i?,65',75)-7-[2-cyanoethoxy(diisopropylamino)phosphinoxy]-l-(4,4'- dimethoxytrityloxymethyl)-3-(4-iV-benzoylcytosin-l-yl)-6-methyl-2,5-dioxa- bicyclo{2.2.1]heptane (44) Scheme 4 (a) TBSC1, EtsN, DMAP.CHaC1a, rt, 16h 97%; (b) POC13,1,2.4-Triazole, EtaN, CH3CN, rt, 4h; (c) Aqueous NH3, 1,4-dioxane, rt, 16h; (d) BZ2O, DMF, rt, 16h, 91% from 39; (e) EtaN.SHF, EtaN, THF, rt, 16h, 87%; (f) CNCH2CH20P(N-iPr2)2, Tetrazole, NMI, DMF, 90%. A) Nucleoside (39) /er^Butyldimethylsilyl chloride (0.45 g, 3.0 mmol) was added to a solution of nucleoside 37 (0.59 g, 1.0 mmol) and imidazole (0.41 g, 6.0 mmol) in DMF (2 mL). After stirring at rt for 16h, the reaction was poured into EtOAc and the organic phase was sequentially extracted with brine, dried (Na2S04) and concentrated under vacuum. Purification by colunm chromatpography (Si02, eluting with 50% EtOAc/hexanes) provided nucleoside 39 (0.68 g, 97%) as a white solid. B) Nucleoside (42) Phosphorus oxychloride (0.74 mL, 8.0 nraiol) was added to a cold (0°C) suspension of 1,2,4-triazole (2.35 g, 34.0 mmol) in CH3CN (16 mL). After stirring for 15 min, triethylamine (5.6 mL, 40 mmol) was added to the reaction and the stirring continued for 30 min. A solution of nucleoside 39 (0.68 g, 1.0 mmol) in CH3CN (7 mL) was added to the reaction at 0°C. After stirring for 10 min, the iC6bath was removed and the reaction was stirred at rt for 4h. The solvent was then removed under vacuum and the residue was partitioned between EtOAc and water. The organic layer was then washed with saturated NaHCOa, brine, dried (Na2S04) and concentrated under vacuum to provide crude 40, which was used without any further purification. Aqueous ammonia (2.5 mL) was added to a solution of nucleoside 40 (from above) in dioxane (12 mL). After stirring at rt for 16h, the reaction was concentrated under vacuum and dried over high vacuum for 8h to provide nucleoside 41, which was used without any further purification. Benzoic anhydride (0.38 g, 1.7 mmol) was added to a solution of nucleoside 41 (from above) in DMF (2 mL). After stirring at rt for 16h, the reaction was poured into EtOAc and the organic layer was extracted with saturated NaHCOs, brine, dried (Na2S04) and concentrated under vacuum. Purification by column chromatography (Si02, eluting with 50% EtOAc/hexanes) provided nucleoside 42 (0.72 g, 91% from 39) as a white solid. C) Nucleoside (43) Triethylamine trihydrofluoride (0.89 mL, 5.5 mmol) was added to a solution of nucleoside 42 (0.72 g, 0.91 mmol) and triethylamine (0.30 mL, 2.2 mmol) in THF (9 mL) a polypropylene tube. After stirring at rt for 16h, the reaction was concentrated under vacuum and the residue was dissolved in EtOAc and the organic layer was sequentially washed with water, saturated NaHCOs, brine, dried (Na2S04) and concentrated under vacuum. Purification by column chromatography (Si02, eluting with 25% to 40% acetone/CHCls) provided nucleoside 43 (0.53 g, 87%) as a white solid. 'H NMR (C6C13): 5 8.34 (s, br, IH), 8.33 (d, IH), 7.83 (d, IH), 7.57-7.26 (m, 16H), 6.89 (d, 4H), 5.72 (s, IH), 4.75 (s, IH), 4.22 (s, IH), 4,14 (m, IH), 3.83 (s, 6H), 3.63 (d, IH), 3.46 (s, IH), 1.20 (d, 3H). D) (15',3iJ,4ii,65,75)-7-[2-Cyaiioethoxy(daisopropyIamino)phosphiiioxy]-l-(4,4'- dimethoxytrityloxymethyl)-3-(4-A'^Beiizoylcytosin-l-yl)-6-metfayl-2,5-dioxa- bicyclo[2.2.1]heptane (44) 2-Cyanoethyl tetraisopropylphorodiamidite (0.37 mL, 1.2 mmol) was added to a solution of nucleoside 43 (0.89 g, 1.3 mmol), tetrazole (43 mg, 0.63 mmol) and TV-methylimidazole (16 H,L, 0.20 mmol) in DMF (4 mL), After stirring at rt for 8h, the reaction was poured into EtOAc and the organic layer was washed with 90% brine, brine, dried (Na2S04) and concentrated. Purification by column chromatography (Si02, eluting with 75% to90% EtOAc/hexanes) provided phosphoramidite 44 as a white solid (0.61 g, 90%)). Example 5 (15,3J?,4if,6-S',750-7-[2-Cyanoethoxy(diisopropylamino)phosphmoxy]-l-(4,4'-dimethoxytrityloxymethyl)-3-(6-A'-benzoyladenm-9-yl)-6-methyI-2,5-dioxa-bicyclo[2.2.1]heptane (51) A) Nucleoside (46) 7V,(9-Bis(trimethylsilyl)acetamide (1.1 mL, 4.50 mmol) was added to a suspension of diacetate 32 (1.0 g, 1.4 mmol) and 6-iV-benzoyladenine (0.48 g, 2.0 nunol) in dichloroethane (14 mL). The reaction mixture turned clear after refluxing 45 minutes and was cooled in an ice bath and trimethylsilyl triflate (0.49 mL, 2.7 mmol) was added. After refluxing for 8 hours the reaction was cooled to room temperature and poured into EtOAc. The organic layer was washed with saturated NaHCOs and brine then dried (Na2S04) and concentrated under vacuum to provide crude nucleoside 45, which was used without purification. K2CO3 (0.38 g, 2.7 mmol) was added to a solution of nucleoside 45 (from above) in MeOH (14 mL). After stirring at room temperature for 24 hours the reaction was concentrated under vacuum. The residue was suspended in EtOAc, extracted with water and brine then dried (Na2S04) and concentrated under vacuum. Purification by column chromatography (SiOi, eluting with 1 to 2.5% MeOH/CHCb) provided nucleoside 46 as a white soHd (0.69 g, 73% firom 32). B) Nucleoside 47 Nucleoside 47 is prepared from nucleoside 46 by reaction with benzoic anhydride (1.5-2 eq) in dry DMF. C) Phosphoramidite 51 Phosphoramidite 51 is prepared from nucleoside 47 using the procedxires illustrated in Example 3 for the phosphoramidite 38 from nucleoside 34. Example 6 (15',3/f,4i2,6J?,75)-7-I2-Cyaiioethoxy(dusopropylainiao)pliosphinoxy]-l-(4,4'-dimethoxytrityloxymethyl)-3-(6-A'-benzoyladenin-9-yI)-6-methyl-2,5-dioxa-bicyclo[2.2.1]heptane (60) A) Diacetate (52) Methanesulfonyl chloride (1.33 mL, 16.8 mmol) was added dropwise to a cold (0 °C) solution of alcohol 28 (7.37 g, 12.0 mmol), triethylamine (2.82 mL, 20.2 mmol) and DMAP (0.20 g, 1.1 mmol) in dichloromethane (25 mL). After stirring for 2 hours at room temperature, the reaction was diluted with dichloromethane and the organic layer was washed with 5% HCl, saturated sodium bicarbonate solution, brine, dried (Na2S04) and concentrated. The crude mesylate 52 thus obtained was used without further purification. B) Diacetate (53) Concentrated sul&ric aC1d (10 drops) was added to a solution of mesylate 52 (from above) in acetic anhydride (7.2 mL) and acetic aC1d (36 mL). After stirring at room temperature for 2 hours the reaction was concentrated under high vacuum. The residue was dissolved in ethyl acetate and the organic layer was carefully washed with water, saturated sodium bicarbonate solution (until pH > 8) and brine then dried (Na2S04) and concentrated. The residue was purified by column chromatography (SiOa, eluting with 25 to 35% EtOAc/hexanes) to provide diacetate 53 (7.66 g, 87% firom 28) as a viscous oil. C) Phosphoramidite (60) Phosphoramidite 60 is prepared from diacetate 53 using the procedures illustrated in Example 3 for the phosphoramidite 51 from diacetate 32. 7V,0-Bis(trimethylsiiyl)acetainide (3.8 mL, 15.5 mmol) was added to a suspension of diacetate 32 (3.44 g, 4.7 mmol) and 2-ainino-6-chloropurine (1.18 g, 7.0 mmol) in dichloroethane (46 mL). After refluxing 45 minutes to get a clear solution, the reaction was cooled in an iC6bath and trimethylsilyl triflate (1.69 mL, 9.4 mmol) was added. After refluxing for 8 hours the reaction was cooled to room temperature and poured into chloroform. The organic layer was washed with saturated NaHCOj and brine then dried (Na2S04) and concentrated under vacuum to provide crude nucleoside 61, which was used widiout purification. B) Nucleoside (62) 3-Hydroxypropionitrile (1.67 mL, 24.5 nmiol) was added dropwise to a stirring suspension of sodium hydride (1.07 g, 27.0 mmol, 60% w/w) in dry THF (10 mL). After stirring for 20 minutes, a solution of crude nucleoside 61 (from above) in dry THF (25 mL) was added. The stirring was continued for 5 hours at room temperature after which, the reaction was careftilly quenched by the addition of a solution of saturated ammonium chloride. The reaction was poured into ethyl acetate and the organic layer was extracted with brine, dried (Na2S04) and concentrated. Purification of the residue by column chromatography (SiOa, eluting with CHC13 to 2.5% MeOH/CHCls) provided nucleoside 62 (3.18 g, 82% fi'om 32) as a light brown solid. C) Nucleoside (63) Isobutyric anhydride (1.5 mL, 9.3 mmol) was added to a solution of nucleoside 62 (3.19 g, 4.6 mmol) and 4-dimethylaminomethylpyridine (0.11 g, 0.93 mmol) in DMF (27 mL). After stirring at 60 °C for 14 hours an additional amount of isobutyric anhydride (1.5 mL, 9.3 ramol) was added to the reaction and the stirring was continued at 60 °C for another 12 hours. The reaction was the cooled to room temperature, diluted with EtOAc and the organic layer was washed with water, saturated sodium bicarbonate solution, brine, dried (Na2S04) and concentrated. Purification by column chromatography (SiOi, 5% to 10% acetone/CHCls) provided nucleoside 63 (2.5 g, 71%) as a yellowish foam. D) Nucleoside (64) DDQ (1.12 g, 5.0 mmol) was added to a solution of nucleoside 63 (2.5 g, 3.3 mmol) in dichloromethane (33 mL) and H2O (1.7 mL). After stirring for 2 hours at room temperature additional DDQ (1.0 g) was added. Stirring was continued at room temperature for another 6 hours after which, the reaction was stored in the refrigerator (4 °C) for 16 hours. The reaction was then concentrated under vacuum and the residue was dissolved in ethyl acetate. The organic layer was washed with water, 10% sodium bisulfite solution (2x), saturated sodium bicarbonate solution and brine then dried (Na2S04) and concentrated. Purification by colximn chromatography (SiOa, eluting with 5% MeOH/CHCB) provided nucleoside 64 (1.84 g, 91%). E) Nucleoside (65) Triethylamine trihydroflouride (2.88 mL, 17.9 mmol) was added to a solution of nucleoside 64 (1.84 g, 3.0 mmol) and triethylamine (1.25 mL, 8.9 mmol) in THF (30 mL) in a polypropylene tube. After stirring at room temperature for 24 hours the reaction was concentrated under vacuum and the residue was dissolved in EtOAc. The organic layer was then washed with water, saturated NaHCOs and brine then dried (Na2S04) and concentrated. Purification by colunrn chromatography (Si02, eluting with 5% to 10% MeOH/CHCb) provided nucleoside 65 (1.05 g, 97%) as a white solid. F) Nucleoside (66) Dimethoxytrityl chloride (1.07 g, 3.2 mmol) was added to a solution of nucleoside 65 (1.00 g, 2.7 mmol) in pyridine (13 mL). After stirring at room temperature for 16 hours the reaction was poured into EtOAc and the organic layer was washed with brine, dried and concentrated. Purification by column chromatography (SiOa, eluting with 2.5 to 5% MeOH/CHCls) provided nucleoside 66 (1.52 g, 85%) as a white foam. G) (15',3J14i?,65',75)-7-[2-Cyanoethoxy(diisopropylainino)phosphinoxy]-l-(4,4'- dimetIioxytrityloxymethyl)-3-(2-7V-Isobutyrylguaniii-9-yl)-6-methyl-2,5-dioxa- bicyclo[2.2.1]heptane (67) 2-Cyanoethyl tetraisopropylphosphordiamidite (1.06 mL, 3.4 mmol) was added to a solution of nucleoside 66 (L52 g, 2.2 mmol), tetrazole (0.12 g, 1.7 mmol) and A'-methylimidazole (45 p,L, 0.56 mmol) in DMF (11 mL). After stirring at room temperature for 8 hours the reaction was poured into EtOAc and the organic layer was washed with 90% brine, brine, dried (Na2S04) and concentrated. Purification by column chromatography (Si02, eluting with 2.5% MeOH/CHCla) provided phosphoramidite 67 as a white solid (1.65 g, 84%). ^^P NMR(C6Cl3)6: 148.70,145.81. Example 8 A) Alcohols (75a-b) Dimethylsulfoxide (3.5 mL, 50.0 mmol) was added to a solution of oxalyl chloride (2.2 mL, 25.0 mmol) in dichloromethane (130 mL) at -78 °C. After stirring for 30 minutes a solution of alcohol 26 (10.0 g, 16.7 mmol) in dichloromethane (30 mL) was added to the reaction over 10 minutes. After stirring for another 45 minutes, triethylamine (10.5 mL, 75.0 mmol) was slowly added to the reaction. After the addition was complete, the ice bath was removed and the reaction was gradually allowed to warm up to 0 °C (ca. 1 hoxir) and transferred to a separatory fiannel. The organic layer was sequentially washed with 5% HCl, a solution of saturated sodium I bicarbonate and brine then dried (Na2S04) and concentrated to provide aldehyde 27, which was dried under high vacuum (18 hours) and used without fiirther purification. A mixture of magnesium turnings (2.5 g, 102.8 mmol) and mercury (11) chloride (93 mg, 0.34 mmol) were covered with dry THF (5 mL) and the reaction was cooled to -20 °C. A few drops of neat methoxymethyl bromide were added to initiate the reaction. After waiting for a few minutes, a solution of methoxymethyl bromide (9.33 mL, 102.8 mmol) in THF (12 mL) was added (1 mL/10 minutes via a syringe) to the reaction over approximately 3 hours. The temperature of the external bath was very carefully maintained between -20 and -25 °C during the addition. A small volume of dry THF (5 mL) was added intermittently (over 3 hours) to the reaction to faC1litate stirring. After the addition of the bromide was complete, the reaction was stirred at -25 °C for 100 minutes and a solution of crude aldehyde (27) in THF (30 mL) was added. After stirring at -20 °C for 45 minutes, no starting aldehyde 27 was detected by TLC. The reaction was carefiiUy quenched with a solution of saturated ammonium chloride and diluted with ethyl acetate. The organic layer was washed with 5% HCl, a saturated solution of sodium bicarbonate and brine then dried (Na2S04) and concentrated. Purification by column chromatography (Si02, eluting with 25 to 30% EtOAc/hexanes) provided alcohols 75a-b (quantitative) as a mixture (ca 1:1 of isomers). B) Mesylates (76a-b) Methanesulfonyl chloride (2.3 mL, 29.2 mmol) was added to a cold (0 °C) solution of alcohols 75a-b (13.38 g, 20.8 mmol) dissolved in triethylamine (5.3 mL, 37.9 mmol) and DMAP (0.36 g, 2.9 mmol) in dichloromethane (42 mL). After stirring for 2 hours additional methanesulfonyl chloride (0.5 mL) was added. Stirring was continued for 1 hour and the reaction was diluted with chloroform. The organic layer was sequentially washed with 5% HCl, a saturated solution of sodium bicarbonate and brine then dried (Na2S04) and concentrated. Purification by column chromatography (SiOa, eluting with 20% EtOAc/hexanes) provide mesylates 76a-b (12.8 g, 85%) as viscous oil C) Diacetates (77a-b) Concentrated sulfiiric aC1d (6 drops) was added to a solution of mesylates 76a-b (12.8 g, 17,8 mmol), acetic aC1d (50 mL) and acetic anhydride (10 mL). After stirring for 3 hours at room temperature the reaction was judged complete by LCMS and the majority of the solvent was evaporated under high vacuum. The concentrated mixture was diluted with ethyl acetate and the organic layer was washed with water, a saturated solution of sodium bicarbonate (until pH >10) and brine then dried (Na2S04) and concentrated. Ptirification by column chromatography (SiOa, eluting with 20% EtOAc/hexanes) provided an anomeric mixture of diacetates 77a-b (11.44 g, 84%) as a viscous oil. D) Nucleosides {79a-b) A^,0-Bis(trimethylsilyl)acetamide (14.76 mL, 59.9 mmol) was added to a suspension of diacetates 77a-b (11.44 g, 15.0 mmol) and uraC1l (3.35 g, 29.9 mmol) in CH3CN (75 mL). After heating at 40 °C for 15 minutes to get a clear solution, the reaction was cooled in an iC6bath and trimethylsilyltriflate (4.06 mL, 22.5 mmol) was added. After refluxing for 2 hours the reaction was cooled to room temperature and poured into EtOAc. The organic layer was washed with half saturated sodium bicarbonate solution and brine then dried (Na2S04) and concentrated under vacuum to provide crude nucleosides 78a-b, which were used without purification. Potassiimi carbonate (5.30 g, 38.4 mmol) was added to a solution of nucleosides 78a-b (from above) in methanol (130 mL). After stirring at room temperature for 16 hours the reaction was concentrated under vacuum. The residue was dissolved in ethyl acetate and extracted with water and brine then dried (Na2S04) and concentrated under vacuum. Purification by column chromatography (Si02, eluting with 5 to 7.5% acetone/chloroform) provided nucleoside 79a-b (9.0 g, 89% from 77a-b) as a white solid. E) Nucleosides (80a and 80b) DDQ (20.0 mmol, 4.5 g) was added to a solution of nucleosides 79a-b (9.0 g, 13.3 mmol) in dichloromethane (130 mL) and water (6.5 mL). Thebiphasic reaction was stirred at room temperature for 2 hours after which additional DDQ (2.75 g was added to the reaction). After another 2 hours additional DDQ (1.1 g) was added to the reaction and the stirring was continued for another 4 hours after which the reaction was stored in a refrigerator for 16 hours. The next morning, LCMS showed traces of nucleosides 79a-b, so additional DDQ (0.9 g) was added to the reaction and the stirring was continued for 2 hours at which point no more nucleosides 79a-b were detected by TLC and LCMS. The solvent was evaporated under vacuum and the residue was partitioned between ethyl acetate and water. The organic layer was washed with sodium bisulfite solution (2x), saturated sodium bicarbonate solution and brine then dried (Na2S04) and concentrated. Purification by column chromatography (Si02, eluting 10 to 20% acetone/chloroform) provided nucleosides 80a (slower running spot) and 80b (faster running spot) respectively (7.0 g combined yield, 98%). F) Nucleoside (81) Triethylamine trihydrofluoride (12.2 mL, 74.8 mmol) was added to a solution of nucleoside 80a (6.7 g, 12.5 mmol) and triethylamine (5.2 mL, 37.4 mmol) in THF (120 mL). After stirring at room temperature for 16 hours the reaction was concentrated to dryness under vacuum. The residue was purified by column chromatography (Si02, eluting with 7.5% to 12.5 % MeOH/CHCb) to provide nucleoside 81 (contaminated with triethylamine.hydroflouride salt, yield >100%), which was used without fiirther purification. G) Nucleoside (82) 4,4'-Dimethoxytrityl chloride (DMTC1, 4.8 g, 14.3 mmol) was added to a solution of nucleoside 81 (~12.5 nxmol) in pjoidine (75 mL). After stirring for 16 hours at room temperature, additional DMTC1 (2.4 g) was added to the reaction. After stirring for another 4 hours MeOH (10 mL) was added. After stirring for 30 minutes, the reaction was diluted with ethyl acetate and the organic layer was washed with water and brine then dried (Na2S04) and concentrated. Purification by column chromatography (Si02, 60 to 75% EtOAc/hexanes) provided nucleoside 82 (6.73 g, 90%) as a white foam. H) (15',3jR,4;2,6i?,75)-7-[2-Cyaiioethoxy(dusopropylamino)phosphmoxy]-l-(4,4'-dimethoxytrityloxymethyl)-3-(uraC1l-l-yl)-6-methoxymethyl-2,5-dioxa-bicyclo(2.2.1]lieptane (83) 2-Cyanoethyl tetraisopropylphosphordiamidite (1.58 mL, 5.0 mmol) was added to a solution of nucleoside 82 (2.0 g, 3.3 mmol), tetrazole (0.19 g, 2.6 mmol) and A'-methylimidazole (68 |a,L, 0.83 mmol) in DMF (16 mL). After stirring at room temperature for 8 hours the reaction was poured into EtOAc. The organic layer was washed with 90% brine followed by brine then dried (Na2S04) and concentrated. Purification by column chromatography (SiOa, eluting with 66% to75% EtOAc/hexanes) provided phosphoramidite 83 as a white solid (2.54 g, 96%). ^'P NMR(C6Cl3) 5: 149.78, 149.44. Example 10 (15',3i?,4if,65,75)-7-[2-Cyanoethoxy(dilsopropylamino)phosphmoxy]-l-(4,4'-dimethoxytrityIoxymethyl)-3-(uraC1l-l-yl)-6-inethoxymethyI-2,5-dioxa-bicyclo-[2.2,l]heptane (86) A) Nucleoside (84) Triethylamine.trihydrofluoride (11.6 mL, 71.5 mmol) was added to a solution of nucleoside 80b (6.43 g, 12.0 mmol) and triethylamine (5.0 mL, 35.7 mmol) in THF (125 mL). After stirring at room temperature for 16 hours the reaction was concentrated to dryness under vacuum. The residue was purified by column chromatography (SiOi, eluting with 7.5% to 12.5 % MeOH/CHClj) to provide nucleoside 84 (contaminated with triethylaminchydroflouride salt, yield >100%), which was used without further purification. B) Nucleoside (85) 4,4'-Dimethoxytrityl chloride (DMTCl, 4.6 g, 13.8 mmol) was added to a solution of nucleoside 84 (~12.0 mmol) in pyridine (72 mL). After stirring for 16 hours at room temperature additional DMTCl (2.3 g) was added to the reaction. After stirring for another 4 hours MeOH (10 mL) was added. After stirring for 30 minutes, the reaction was diluted with ethyl acetate and the organic layer was washed with water and brine then dried (Na2S04) and concentrated. Purification by column chromatography (Si02, 60 to 75% EtOAc/hexanes) provided nucleoside 85 (6.52 g, 91%) as a white foam. C) (15',3i?,4i2,65',75)-7-[2-Cyanoethoxy(diisopropylamiiio)phosphiiioxy]-l-(4,4'- dimethoxytrityioxymethyI)-3-(uraC1l-l-yl)-6-methoxymethyI-2,5-dioxa- bicyclo[2.2.1]heptane (86) 2-Cyanoethyl tetraisopropylphosphordiamidite (1.58 mL, 5.0 mmol) was added to a solution of nucleoside 85 (2.0 g, 3.3 mmol), tetrazole (0.19 g, 2.7 mmol) and A'-methylimidazole (68 fiL, 0.83 nrniol) in DMF (17 mL). After stirring at room temperature for 8 hours the reaction was poured into EtOAc. The organic layer was washed with 90% brine then brine and dried (Na2S04) and concentrated. Purification by column chromatography (Si02, eluting with 66% to75% EtOAc/hexanes) provided phosphoramidite 86 as a white solid (2.55 g, 96%). ^'P NMR (C6C13) 6: 149.97, 149.78. (A) Nucleoside (87) /err-Butyldimethylsilyl chloride (2.40 g, 15.9 mmol) was added to a solution of nucleoside 82 (3.20 g, 5.3 mmol) and imidazole (2.16 g, 31.8 mmol) in DMF (10.6 mL). After stirring at room temperature for 16 hours the reaction was poured into EtOAc. The organic phase was sequentially extracted with brine, dried (Na2S04) and concentrated under vacuum. Purification by column chromatography (SiOi, eluting with 50% EtOAc/hexanes) provided nucleoside 87 (3.70 g, 98%) as a white solid. B) Nucleoside (90) Phosphorus oxychloride (3.86 mL, 41.4 mmol) was added to a cold (0 °C) suspension of 1,2,4-triazole (12.15 g, 176.1 mmol) in CH3CN (80 mL). After stirring for 15 minutes triethylamine (29.0 mL, 207.2 mmol) was added and the stirring was continued for 30 minutes. A solution of nucleoside 87 (3.70 g, 5.2 mmol) in CH3CN (20 mL) was added to the reaction mixture at 0 °C. After stirring for 10 minutes the iC6bath was removed and the reaction was stirred at room temperature for 4 hours. The solvent was removed under vacuum and the residue was partitioned between EtOAc and water. The organic layer was then washed with saturated NaHCOj and brine then dried (Na2S04) and concentrated under vacuum to provide crude 88, which was used without fiarther purification. Aqueous anamonia (10 mL) was added to a solution of nucleoside 88 (firom above) in dioxane (50 mL). After stirring at room temperature for 16 hours the reaction was concentrated under vacuiun and dried over high vacuum for 8 hours to provide nucleoside 89, which was used without fiirther purification. Benzoic anhydride (1.99 g, 8.8 mmol) was added to a solution of nucleoside 89 (from above) in DMF (10 mL). After stirring at room temperature for 16 hours the reaction was poured into EtOAc. The organic layer was extracted with saturated NaHCOs and brine then dried (Na2S04) and concentrated under vacuum. Purification by column chromatography (SiOa, eluting with 50% EtOAc/hexanes) provided nucleoside 90 (3.86 g, 91% from 87) as a white solid. C) Nucleoside (91) Triethylamine trihydrofluoride (4.54 mL, 27.9 mmol) was added to a solution of nucleoside 90 (3.81 g, 4.7 mmol) and triethylamine (1.56 mL, 11.2 mmol) in THF (46 mL) a polypropylene tube. After stirring at room temperature for 16 hours the reaction was dried under vacuum and the residue was dissolved in EtOAc. The organic layer was sequentially washed with water, saturated NaHCOs and brine then dried (Na2S04) and concentrated under vacuum. Purification by column chromatography (SiOi, eluting with 5% MeOH/CHCb) provided nucleoside 91 (3.07 g, 94%) as a white solid. D) (15,3iZ,4i?,6ii,75)-7-[2-Cyaiioethoxy(diisopropylaiiimo)phosphm oxy]-l-(4,4'- dimethoxytrityloxymethyl)-3-(4-A'-Ben2oylcytosm-l-yl)-6-methyI-2,5-dioxa- bicyclo[2.2.1]heptane (92) 2-Cyanoethyl tetraisopropylphosphordiamidite (0.90 mL, 4.3 mmol) was added to a solution of nucleoside 91 (2.0 g, 2.8 mmol), tetrazole (0.16 g, 2.3 mmol) and TsT-methylimidazole (58 ^L, 0.71 mmol) in DMF (14 mL). After stirring at room temperature for 8 hours the reaction was poured into EtOAc. The organic layer was washed with 90% brine followed by brine then dried (Na2S04) and concentrated. The residue was dissolved in minimum amount of EtOAc and this solution was added to hexanes. The resulting preC1pitate was collected and further purified by column chromatography (Si02, eluting with 75% to 90% EtOAc/hexanes) to provide phosphoramidite 92 as a white solid (2.14 g, 84%). ^'P NMR (C6C13) 5:149.82. fer^ButyldimethylsilyI chloride (2.25 g, 15.0 mmol) was added to a solution of nucleoside 85 (3.0 g, 5.0 mmol) and imidazole (2.03 g, 29.9 mmol) in DMF (10 mL). After stirring at room temperature for 16 hours the reaction was poiired into EtOAc. The organic phase was sequentially extracted with brine, dried (Na2S04) and concentrated under vacuum. Purification by column chromatography (Si02, eluting with 50% EtOAc/hexanes) provided nucleoside 93 (3.45 g, 97%) as a white solid. B) Nucleoside (96) Phosphorus oxychloride (3.59 mL, 38.5 mmol) was added to a cold (0 °C) suspension of l,2,4-tria2ole (11.3 g, 163.9 mmol) in CH3CN (80 mL). After stirring for 15 minutes triethylamine (27.0 mL, 192.8 mmol) was added to the reaction and the stirring continued for 30 minutes. A solution of nucleoside 93 (3.45 g, 4.82 mmol) in CH3CN (20 mL) was added to the reaction at 0 °C. After stirring for 10 minutes the iC6bath was removed and the reaction was stirred at room temperature for 4 hours. The solvent was then removed under vacuum and the residue was partitioned between EtOAc and water. The organic layer was then washed with a saturated solution of NaHCOa and brine then dried (Na2S04) and concentrated under vacuum to provide crude 94, which was used without fiirther purification. Aqueous ammonia (10 mL) was added to a solution of nucleoside 94 (from above) in dioxane (50 mL). After stirring at room temperature for 16 hours the reaction was concentrated under vacuum and dried over high vacuum for 8 hours to provide nucleoside 95, which was used without further purification. Benzoic anhydride (1.63 g, 7.2 mmol) was added to a solution of nucleoside 95 (from above) in DMF (9 mL). After stirring at room temperature for 16 hours the reaction was poured into EtOAc. The organic layer was extracted with saturated NaHCOs and brine then dried (Na2S04) and concentrated under vacuum. Purification by column chromatography (Si02, eluting with 50% EtOAc/hexanes) provided nucleoside 96 (3.53 g, 89% fi-om 93) as a white solid. C) Nucleoside (97) Triethylamine trihydrofluoride (4.20 mL, 25.8 mmol) was added to a solution of nucleoside 96 (3.53 g, 4.3 mmol) and triethylamine (1.43 mL, 10.3 mmol) in THF (43 mL) in a polypropylene tube. After stirring at room temperature for 16 hours the reaction was dried under vacuum and the residue was dissolved in EtOAc. The organic layer was sequentially washed with water, saturated NaHCOj and brine then dried (Na2S04) and concentrated under vacuum. Purification by column cliromatography (SiOa, eluting with 25% to 40% acetone/CHCls) provided nucleoside 97 (2.87 g, 95%) as a white soHd. D) (15',3;?,4J?,65',7^-7-[2-eyanoethoxy(diisopropylammo)phosphm oxy]-l-(4,4'- dimethoxytrityloxymethyl)-3-(4-A'^Beiizoylcytosm-l-yl)-6-methyI-2,5-dioxa-bicyclo[2.2.1]heptane (98) 2-Cyanoethyl tetraisopropylphosphordiamidite (1.35 mL, 4.3 mmol) was added to a solution of nucleoside 97 (2.0 g, 2.8 nimol), tetrazole (0.16 mg, 2.3 mmol) and N-methylimidazole (58 ^xL, 0.71 mmol) in DMF (14 mL). After stirring at room temperature for 8 hours the reaction was poured into EtOAc and the organic layer was washed with 90%) brine followed with brine then dried (Na2S04) and concentrated. Purification by column chromatography (Si02, eluting with 75%) to 90%o EtOAc/hexanes) provided phosphoramidite 98 as a white solid (2.15 g, 84%). ^'P NMR (C6C13) 6: 150.33. Example 13 (15,3if,4i!:,6if,75)-7-[2-Cyanoethoxy(diisopropylammo)phosphuioxy]-l-(4,4'-dimethoxytrityloxymethyl)-3-(6-A'-BenzoyIadenm-9-yl)-6-methoxymethyI-2,5-dioxa-bicyclo[2.2.1]heptane (105) A) Nucleoside 118 Dimethylsulfoxide (1.77 mL, 25.0 mmol) was added dropwise to a cold (-78° C) solution of oxalyl chloride (1.10 mL, 12.5 mmol) in dichloromethane (60 mL). After stirring for 30 minutes, a solution of alcohol 26 (5.0 g, 8.4 mmol) in dichloromethane (20 mL) was added to the reaction. The stirring was continued at -78 °C for another 45 minutes after which, triethylamine (5.05 mL, 37.5 mmol) was added dropwise to the reaction. After strring for 10 minutes, the iC6bath was removed and the reaction was allowed to warm gradually to ca. 0 °C at whichT1me, TLC analysis indicated no starting alcohol. The reaction was diluted with dichloromethane and the organic layer was sequentially washed with 10% HCl, saturated NaHCOs, brine, dried (Na2S04) and concentrate to provide aldehyde 27, which was used for the next step without any purification. B) Nucleoside 118 ! nBuLi (2.5 M, 4.34 mL, 10.9 mmol) was added dropwise to a cold (0° C) stirring solution of triphenylphosphonium bromide (3.88 g, 10.9 mmol) in dry THF (60 mL). After stirring for 1 hour, the red solution was cooled to -78 °C and a solution of aldehyde 27 from above (8.4 mmol) in dry THF (15 mL) was added dropwise to the reaction. The reaction was gradually allowed to warm to room temperature and the stirring was continued for another 16 hours. The reaction was I then carefully quenched using saturated NH4C1 and partitioned between EtOAc and water. The organic layer was sequentially washed with brine, dried (Na2S04) and concentrated. Purification by column chromatography (Si02, eluting with 10 % EtOAc in hexanes) provided olefin 118 (4.84 g, 97% fi-om 26) as a colorless oil. C) Nucleoside 119 Tetrabutylammonium fluoride (IM in THF, 10.00 mL, 10.0 mmol) was added to a solution of olefin 118 (4.83 g, 8.1 mmol) in THF (35 mL). The reaction was stirred at room temperature for 16 hours after which the solvent was removed under vacuum and the residue was dissolved in EtOAc. The organic layer was washed with water, brine, dried (Na2S04) and concentrated. Purification by column chromatography (SiOa, eluting with 40 % EtOAc in hexanes) provided alcohol 119 (2.79 g, 97%) as a colorless oil. D) Nucleoside 120 Sodium hydride (60% w/w in mineral oil, 0.4 g, 10 mmol) was added to a cold (0° C) solution of alcohol 119 (1.44 g, 4.1 namol) and benzyl bromide (0.71 mL, 6.0 mmol) in DMF (16 mL). After stirring for 1 hour at 0 °C, the reaction was carefiiUy quenched with water and partitioned between EtOAc and water. The organic layer was separated and washed with brine, dried (Na2S04) and concentrated. Purification by column chromatography (Si02, eluting with 10 to 25% EtOAc in hexanes) provided olefin 120 (1.84 g, quantitative) as a colorless oil. E) Nucleoside 121 Osmium Tetroxide (OSO4, 25% solution in iPrOH, ImL) was added to a solution of olefin 120 (1.80 g, 4.0 mmol) and iV-methylmorpholine-iV-oxide (NMO, 0.94 g, 8.0 mmol) in 95% acetone/water (25 mL). After stirring for 16h at room temperature, additional OSO4 solution (0.5 mL) and NMO (0.40 g) were added to the reaction. After stirring for a total 48 hours, the reaction was diluted with EtOAc and washed with 10% NaHSOj, brine, dried (Na2S04) and concentrated. Purification by column chromatography (SiOa, eluting with 40 to 50% EtOAc in hexanes) provided diol 121 (1.68 g, 87%, ca. 1:1 mixture of isomers) as a colorless oil. F) Nucleosides 122 and 123 TBSCl (0. 66 g, 4.4 irnnol) was added to a cold (0 °C) solution of diol 121 (1.63 g, 3.4 mmol) in pyridine (17 mL). After stirring for 4 h at 0 °C, the reaction was diluted with EtOAc and the organic layer was washed with water, brine, dried and concentrated. Purification by column chromatography (Si02, eluting with 10 to 20%o EtOAc in hexanes) provided alcohols 122 and 123 (0.90 g and 1.17 g, absolute stereochemistry not assigned) as colorless oils. G) Nucleoside 124 Methanesulfonyl chloride (0.24 mL, 3.0 nrniol) was added dropwise to a cold (0 °C) solution of alcohol 123 (absolute stereochemistry not assigned, 0.9 g, 1.5 mmol), triethylamine (0.46 mL, 3.3 mmol) and dimethylaminopyridine (37 mg, 0.3 mmol) in dichloromethane (5 mL). After 7 hours at room temperature, additional methansulfonyl chloride (0.12 mL) and triethylamine (0.23 mL) were added to the reaction. After stirring for another 9 hours at room temperature, the reaction was poured into EtOAc and the organic layer was washed with 10% HCl, saturated NaHCOs, brine, dried (Na2S04) and concentrated. Purification by column chromatography (SiOz, eluting with 10 to 15% EtOAc in hexanes) provided mesylate 124 (0.44 g, 44%) and starting diol 123 (0.32 g, 40%). H) Nucleoside 125 Triethylamine trihydroflouride (0.64 mL, 4.0 mmol) was added to a solution of mesylate 124 (0.44 g, 0.6 mmol) and triethylamine (0.23 mL, 1.7 mmol) in THF (7 mL). After stirring for 16 hours at room temperature, the reaction was diluted vwth EtOAc and the organic phase was washed with saturated NaHCOs, brine, dried (Na2S04) and concentrated. Purification by column chromatography (SiOz, eluting with 50%i EtOAc in hexanes) provided alcohol 125 (0.40 g, quantitative). I) Nucleoside 127 PivaloyI chloride (0.12 mL, 1.0 mmol) was added dropwise to a cold (0 "C) solution of alcohol 125 (0.72 mmol, 0.4 g), diisopropylethylamine (DIPEA, 0.17 mL, 1.0 mmol) and dimethylaminopyridine (12 mg, 0.1 mmol) in dichloromethane (2 mL). The iC6bath was then removed and the reaction was stirred at room temperature for 2 hours after which additional DIPEA (0.17 mL) and pivaloyl chloride (0.12 mL) was added and the reaction was stirred at room temperature for 16 hours. The reaction was then diluted with EtOAc and the organic layer was washed with 10% HCl, saturated NaHCOs, brine, dried (Na2S04) and concentrated to provide crude pivaloate 126, which was used without any further purification. Concentrated sulfuric aC1d (2 drops) was added to a solution of crude pivaloate 126 (from above) in glaC1al acetic aC1d (2.5 mL) and acetic anhydride (0.5 mL). After stirring at room temperature for 2 hours, the solvent was removed xmder high vacuum and the residue was dissolved in EtOAc and the organic layer was washed with saturated NaHCOs, brine, dried (Na2S04) and concentrated. Purification by colunm chromatography (Si02, eluting with 10 to 15% EtOAc in hexanes) provided diacetate 127 (0.45 g, 92% from 125) as a colorless oil (mixture of anomers). J) Nucleoside 129a A',0-Bis(trimethylsilyl)acetamide (0.8 mL, 3.3 mmol) was added to a suspension of diacetate 127 (0.45 g, 0.65 mmol) and uraC1l (0.15 g, 1.3 mmol) in CH3CN (3.5 mL). After heating at 40°C for 15 min to get a clear solution, trimethylsilyl fcriflate (0.24 mL, 1.3 mmol) was added to the reaction. After refluxing for 2 hours, the reaction was cooled to room temperature and poiu-ed into EtOAc. The organic layer was washed with saturated NaHCOs, brine, dried (Na2S04) and concentrated under vacuum to provide crude nucleoside 128a, which was used without any purification. K2CO3 (40 mg, 0.3 mmol) was added to a solution of nucleoside 128a (0.11 g, 0.15 mmol) in MeOH (1.5 mL), After stirring for 16h at room temperature, the solvent was removed under vacuum and the residue was partitioned between EtOAc and brine. The organic phase was collected, dried (Na2S04) and concentrated, under vacuum to provide 129a (absolute stereochemistry not determined). Purification by column chromatography (Si02, eluting with 35% acetone in CHC13) provided nucleoside 129a (57 mg, 74% from 127). ^H NMR (C6C13): 5 9.37 (s, IH), 7.92-7.61 (m, 5H), 7.55-7.23 (m, 9H), 5.58 (s, IH), 5.43 (d, IH, J= 8.1), 4.79 (d, IH, J= 11.7), 4.66 (d, IH, J= 11.7), 4.58 (m, 2H), 4.51 (s, IH), 4.44 (m, IH), 4.05 (s, IH), 3.95-3.72 (m, 4H). LCMS: retentionT1me 3.34 min; M+H calC6. 517.19, found 517.1. Nucleosides 128b, 128c and 128d are prepared from sugar precursor 127 by a Vorbrugen reaction using A/^-Bz-cytosine, 6-iV-Bz-adenine and 2-ainino-6-chloropurine respectively (Scheme 18). Treatment of 128b and 128c with K2CO3 and MeOH provides nucleosides 129b and 129c respectively. Treatment of 128d with sodium hydride and S-hydroxypropionitrile provides nucleoside 129d. Transient protection of the hydroxyl group with TMSCl followed by reaction with benzoyl chloride provides nucleosides 130b and 130c respectively. Alternatively the above transformation can also be accomplished by reacting nucleosides 129b and 129c with benzoic anhydride using DMF as the solvent. Nucleoside 130d is prepared by transient protection with excess TMSCl in pyridine followed by reaction with isobutyryl chloride. or under Swem conditions followed by reductive amination of the resulting aldehyde with a primary or a secondary amine in the presenC6of glaC1al acetic aC1d and a reduC1ng agent such as sodium cyanoborohydride. Nucleoside 134 is prepared from 130 by converting the hydroxy! group to a leaving group (mesylate, tosylate, halide) followed by heating with excess sodium azide. Nucleoside 135 is prepared from 130 by oxidation of the primary alcohol to a carboxylic aC1d followed by reaction with a amine in the presenC6of HATU or any other peptide coupling reagent. Nucleoside 136 is prepared from 130 by activating the hydroxyl group with carbonyl dimimdazole followed by reaction with a amine. Nucleoside 137 is prepared from 130 by deprotonating the hydroxyl group with an appropriate base followed by quenching the anion with an alkylating reagent. Nucleoside 138 is prepared from 130 by converting the hydroxyl group to a leaving group followed by displacement with a thiol nucleophile. Nucleoside 139 is prepared from 134 by reduction of the azide group followed by reaction with an isocyanate or an isothiocyanate. Nucleoside 140 is prepared from 134 by reduction of the azido group and reaction with FmocNC6 to provide an activated thiourea. Further reaction of the finoc activated thiourea with an amine in the presenC6of EDC provides the substituted guanidine. Removal of the finoc protecting group liberates nucleoside 140. first removing the 3'(9-Nap group with DDQ followed by a catalytic hydrogenation to remove the 5'0-benzyl group. Subsequent protection of the 5' hydroxyl group as the dimethoxytrityl ether followed by a phosphitilation reaction provides phosphoramidite 143. A) Nucleoside (131a). Diethylaminosulfurtrifluoride (DAST, 0.16 mL, 1.4 nunol) was added to a cold (-50°C) solution of nucleoside 129a (0.1 g, 0.2 mmol) in dichloromethane (2 mL). The reaction was gradually warmed to room temperature and stirred 16 hours after which, it was carefully quenched with saturated NaHCOs solution. The reaction was then partitioned between EtOAc and brine, dried (Na2S04) and concentrated. Purification by column chromatography (SiOa, 33% EtOAc in hexanes) provided nucleoside 131a (51 mg, 52%, contaminated with 15-20% of a ring opened impurity) as a mixture of isomers.). ^'F NMR (C6C13): 6 -227.98 (m) and -231.07 (m). LCMS: retentionT1me 3.84 min; M+H calC6. 519.19, found 519.1 and 3.89 min; M+H calC6. 519.19, found 519.1. B) Nucleoside (141a). DDQ (44 mg, 0.2 mmol) was added to a solution of nucleoside 131a (51 mg, 0.1 ramol) in dichloromethane (1 mL) and water (2 drops). After stirring at room temperature for 8 hours, the reaction was diluted with EtOAc and the organic phase was washed with 10% NaHSOs solution, saturated NaHCOs solution, brine, dried (Na2S04) and concentrated. Purification by column chromatography (SiOi, 30% acetone in chloroform) provided nucleoside 141a (41 mg, quantitative as a mixture of isomers.). '^F NMR (C6C13): 5 -229.3 (t) and -230.97 (dt). LCMS: retentionT1me 2.66 min; M+H calC6. 379.12, found 379.0 C) Nucleoside (142a). A mixture of nucleoside 141a (41 mg, from above) and 10% palladium on charcoal (10 mg) in methanol (2 mL) was hydrogenated using a hydrogen balloon. After 3 hours, all starting nucleoside 141a was consumed (as indicated by LCMS analysis of the reaction mixture). The reaction was filtered through celite and the filtrate concentrated under reduced pressure. Purification by column chromatography (SiOs, 10 to 20% methanol in chloroform) provided nucleoside 142a (14 mg, 50%) as a mixture of isomers. ^'F NMR (C6C13): 5 -231.45 (t) and -232.88 (dt). LCMS: retentionT1me 1.72 min; M+Na calC6. 311.08, found 311.0. D) Nucleoside (142aa). DMTCl (24 mg, 0.07 mmol) was added to a solution of nucleoside 142a (14 mg, 0.049 mmol) in pyridine (0.25 mL). After stirring at room temperature for 3 hoiirs, the reaction was concentrated under reduced pressure. Purification by column chromatography (Si02,20 to 30% acetone in chloroform) provided nucleoside 142aa (16 mg, 55%)) as a mixture of isomers. '^F NMR (C6C13): 5 -228.6 (t) and -230.91 (dt). LCMS: retentionT1me 3.56 min; M+Na calC6. 613.21, found 613.1. E) Amidite (143a). Amidite 143a is prepared from nucleoside 142aa using a phosphitilation reaction as described in example 1. Example 22 Synthesis of Nucleoside Phosphoramidites The preparation of nucleoside phosphoramidites is performed following procedures that are illustrated herein and in the art such as but not limited to US Patent 6,426,220 and published PCT WO 02/36743. Example 23 Oligonucleotide and oligonucleoside synthesis The oligomeric compounds used in accordanC6with this invention may be conveniently and routinely made through the well-known technique of solid phase synthesis. Equipment for such synthesis is sold by several vendors including, for example. Applied Biosystems (Foster C1ty, CA). Any other means for such synthesis known in the art may additionally or alternatively be employed. It is well known to use similar techniques to prepare oligonucleotides such as the phosphorothioates and alkylated derivatives. Oligonucleotides: Unsubstituted and substituted phosphodiester (P=0) oligonucleotides can be synthesized on an automated DNA synthesizer (Applied Biosystems model 394) using standard phosphoramidite chemistry with oxidation by iodine. Phosphorothioates (P=S) are synthesized similar to phosphodiester oligonucleotides with the following exceptions: thiation is effected by utilizing a 10% w/v solution of 3 ,H-1,2-benzodithiole-3 -one 1,1 -dioxide in acetonitrile for the oxidation of the phosphite linkages. The thiation reaction stepT1me is increased to 180 sec and preceded by the normal capping step. After cleavage from the CPG column and deblocking in concentrated ammonium hydroxide at 55°C (12-16 hr), the oligonucleotides are recovered by preC1pitating with greater than 3 volumes of ethanol from a 1 M NH4OAC solution. Phosphinate oligonucleotides can be prepared as described in U.S. Patent 5,508,270. Alkyl phosphonate oligonucleotides can be prepared as described in U.S. Patent 4,469,863. 3'-Deoxy-3'-methylene phosphonate oligonucleotides can be prepared as described in U.S. Patents 5,610,289 or 5,625,050. Phosphoramidite oligonucleotides can be prepared as described in U.S. Patent, 5,256,775 or U.S. Patent 5,366,878. Alkylphosphonothioate oligonucleotides can be prepared as described in pubHshed PCX applications PCT/US94/00902 and PCT/US93/06976 (published as WO 94/17093 and WO 94/02499, respectively). 3'-Deoxy-3'-amino phosphoramidate oligonucleotides can be prepared as described in U.S. Patent 5,476,925. Phosphotriester oligonucleotides can be prepared as described in U.S. Patent 5,023,243. Borano phosphate oligonucleotides can be prepared as described in U.S. Patents 5,130,302 and 5,177,198. OHgonucleosides: Methylenemethylimino linked oligonucleosides, also identified as MMI Hnked oligonucleosides, methylenedimethylhydrazo linked oligonucleosides, also identified as MDH linked oligonucleosides, and methylenecarbonylamino linked oligonucleosides, also identified as amide-3 linked oligonucleosides, and methyleneaminocarbonyl linked oligonucleosides, also identified as amide-4 linked oligonucleo¬sides, as well as mixed backbone oligomeric compounds having, for instance, alternating MMI and P=0 or P=S linkages can be prepared as described in U.S. Patents 5,378,825; 5,386,023; 5,489,677; 5,602,240 and 5,610,289. Formacetal and thioformacetal linked oligonucleosides can be prepared as described in U.S. Patents 5,264,562 and 5,264,564. Ethylene oxide linked oligonucleosides can be prepared as described in U.S. Patent 5,223,618. Example 24 Oligonucleotide Isolation After cleavage from the controlled pore glass solid support and deblocking in concentrated ammonium hydroxide at 55°C for 12-16 hours, the oligonucleotides or oHgonucleosides are recovered by preC1pitation out of 1 M NH4OAC with >3 volumes of ethanol. Synthesized oligonucleotides are analyzed by electrospray mass spectroscopy (molecular weight determination) and by capillary gel electrophoresis. The relative amounts of phosphorothioate and phosphodiester linkages obtained in the synthesis is determined by the ratio of correct molecular weight relative to the -16 amu product (+/-32 +/-48). For some studies oligonucleotides are purified by HPLC, as descrilsed by Chiang at al., J. Biol. Chem. 1991, 266, 18162-18171. Results obtained with HPLC-purified material are generally similar to those obtained with non-HPLC purified material. Example 25 Oligonucleotide Synthesis - 96 Well Plate Format Oligonucleotides can be synthesized via solid phase P(III) phosphoramidite chemistry on an automated synthesizer capable of assembling 96 sequences simultaneously in a 96-well format. Phosphodiester intemucleotide linkages are afforded by oxidation with aqueous iodine. Phosphorothioate intemucleotide linkages are generated by sulfurization utilizing 3,H-1,2 benzodithiole-3-one 1,1 dioxide (Beaucage Reagent) in anhydrous acetonitrile. Standard base-protected beta-cyanoethyl-diiso-propyl phosphoramidites are purchased from commerC1al vendors (e.g. PE-Applied Biosystems, Foster C1ty, CA, or PharmaC1a, Piscataway, NJ). Non¬standard nucleosides are synthesized as per standard or patented methods. They are utilized as base protected beta-cyanoethyldiisopropyl phosphoramidites. Oligonucleotides are cleaved frorn support and deprotected with concentrated NH4OH at elevated temperature (55-60°C) for 12-16 hours and the released product then dried in vacuo. The dried product is then re-suspended in sterile water to afford a master plate from which all analytical and test plate samples are then diluted utilizing robotic pipettors. Example 26 Oligonucleotide Analysis using 96-Well Plate Format The concentration of oligonucleotide in each well is assessed by dilution of samples and UV absorption spectroscopy. The fiill-length integrity of the individual products is evaluated by capillary electrophoresis (CE) in either the 96-well format (Beckman P/ACE™ MDQ) or, for individually prepared samples, on a commerC1al C6apparatus (e.g., Beckman P/ACE™ 5000, ABI270). Base and backbone composition is confirmed by mass analysis of the oligomeric compounds utilizing electrospray-mass spectroscopy. All assay test plates are diluted from the master plate using single and multi-channel robotic pipettors. Plates are judged to be acceptable if at least 85% of the oligomeric compounds on the plate are at least 85% full length. Example 27 Cell culture and oligonucleotide treatment The effect of oligomeric compounds on target nucleic aC1d expression can be tested in any of a variety of cell types provided that the target nucleic aC1d is present at measurable levels. This can be routinely determined using, for example, PCR or Northern blot analysis. Cell lines derived from multipleT1ssues and speC1es can be obtained from American Type Culture Collection (ATCC, Manassas, VA). The following cell type is provided for illustrative purposes, but other cell types can be routinely used, provided that the target is expressed in the cell type chosen. This can be readily determined by methods routine in the art, for example Northern blot analysis, ribonuclease protection assays or RT-PCR. b.END cells: The mouse brain endothelial cell Une b.END was obtained from Dr. Werner Risau at the Max Plank Institute (Bad Nauheim, Germany). b.END cells were routinely cultured in DMEM, high glucose (Invitrogen Life Technologies, Carlsbad, CA) supplemented with 10% fetal bovine serum (Invitrogen Life Technologies, Carlsbad, CA). Cells were routinely passaged by trypsinization and dilution when they reached approximately 90% confluence. Cells were seeded into 96-well plates (Falcon-Primaria #353872, BD BiosC1ences, Bedford, MA) at a density of approximately 3000 cells/well for uses including but not limited to oligomeric compound transfection experiments. Experiments involving freatment of cells with oligomeric compounds: When cells reach appropriate confluency, they are treated with oligomeric compounds using a transfection method as described. LIPOFECTIN™ When cells reached 65-75% confluency, they are treated with oligonucleotide. Oligonucleotide is mixed with LIPOFECTIN'"'^ Invitrogen Life Technologies, Carlsbad, CA) in Opti-MEIvr'^-1 reduced serum medium (Invitrogen Life Technologies, Carlsbad, CA) to achieve the desired concentration of oligonucleotide and a LIPOFECTIN'^'^ concentration of 2.5 or 3 fig/mL per 100 nM oligonucleotide. This transfection mixture is incubated at room temperature for approximately 0.5 hours. For cells grown in 96-well plates, wells are washed onC6with 100 |iL OPTI-MEM™-! and then treated with 130 |iiL of the transfection mixture. Cells grown in 24-well plates or other standardT1ssue culture plates are treated similarly, using appropriate volumes of medium and oligonucleotide. Cells are treated and data are obtained in duplicate or triplicate. After approximately 4-7 hours of treatment at 37°C, the medium containing the transfection mixture is replaced with fresh culture medium. Cells are harvested 16-24 hours after oligonucleotide treatment. Other suitable transfection reagents known in the art include, but are not limited to, CYTOFECTIN™, LIPOFECTAMINE™, OLIGOFECTAMINE™, and FUGENE™. Other suitable transfection methods known in the art include, but are not limited to, electroporation. Example 28 Analysis of oligonucleotide inhibition of a target expression Antisense modulation of a target expression can be assayed in a variety of ways known in the art. For example, a target mRNA levels can be quantitated by, e.g., Northern blot analysis, competitive polymerase chain reaction (PCR), or real-time PCR. Real-time quantitative PCR is presently desired. RNA analysis can be performed on total cellular RNA or poly(A)+ mRNA. One method of RNA analysis of the present invention is the use of total cellular RNA as described in other examples herein. Methods of RNA isolation are well known in the art. Northern blot analysis is also routine in the art. Real-time quantitative (PCR) can be conveniently accomplished using the commerC1ally available ABI PRISM™ 7600, 7700, or 7900 SequenC6Detection System, available from PE-Applied Biosystems, Foster C1ty, CA and used according to manufacturer's instructions. Protein levels of a target can be quantitated in a variety of ways well known in the art, such as immunopreC1pitation, Western blot analysis (immunoblotting), enzyme-linked immunosorbent assay (ELISA) or fluorescence-activated cell sorting (FAC6). Antibodies directed to a target can be identified and obtained from a variety of sources, such as the MSRS catalog of antibodies (Aerie Corporation, Birmingham, MI), or can be prepared via conventional monoclonal or polyclonal antibody generation methods well known in the art. Methods for preparation of polyclonal antisera are taught in, for example, Ausubel, F.M. et al., Current Protocols in Molecular Biology, Volume 2, pp. 11.12.1 -11.12.9, John Wiley & Sons, Inc., 1997. Preparation of monoclonal antibodies is taught in, for example, Ausubel, F.M. et al, Current Protocols in Molecular Biology, Volume 2, pp. 11.4.1 -11.11.5, John Wiley & Sons, Inc., 1997. ImmunopreC1pitation methods are standard in the art and can be found at, for example, Ausubel, F.M. et al., Current Protocols in Molecular Biology, Voltmie 2, pp. 10.16.1-10.16.11, John Wiley & Sons, Inc., 1998. Western blot (immunoblot) analysis is standard in the art and can be found at, for example, Ausubel, F.M. et al.. Current Protocols in Molecular Biology, Volume 2, pp. 10.8.1-10.8.21, John Wiley & Sons, Inc., 1997. Enzyme-linked immunosorbent assays (ELISA) are standard in the art and can be found at, for example, Ausubel, F.M. et al., Current Protocols in Molecular Biology, Volume 2, pp. 11.2.1-11.2.22, John Wiley & Sons, hic, 1991. Example 29 Design of phenotypic assays and in vivo studies for the use of target inhibitors Phenotypic assays OnC6target inhibitors have been identified by the methods disclosed herein, the oligomeric compounds are further investigated in one or more phenotypic assays, each having measurable endpoints predictive of efficacy in the treatment of a particular disease state or condition. Phenotypic assays, kits and reagents for their use are well known to those skilled in the art and are herein used to investigate the role and/or assoC1ation of a target in health and disease. Representative phenotypic assays, which can be purchased from any one of several commerC1al vendors, include those for determining cell viability, cytotoxiC1ty, proliferation or cell survival (Molecular Probes, Eugene, OR; PerkinElmer, Boston, MA), protein-based assays including enzymatic assays (Panvera, LLC, Madison, WI; BD BiosC1ences, Franklin Lakes, NJ; Oncogene Research Products, San Diego, CA), cell regulation, signal transduction, inflammation, oxidative processes and apoptosis (Assay Designs Inc., Ann Arbor, MI), triglyceride accumulation (Sigma-Aldrich, St. Louis, MO), angiogenesis assays, tube formation assays, cytokine and hormone assays and metabolic assays (Chemicon International Inc., Temecula, CA; Amersham BiosC1ences, Piscataway, NJ). In one non-limiting example, cells determined to be appropriate for a particular phenot>pic assay (i.e., MCF-7 cells selected for breast cancer studies; adipocytes for obesity studies) are treated with a target inhibitors identified from the in vitro studies as well as control compounds at optimal concentrations which are determined by the methods described above. At the end of the treatment period, treated and untreated cells are analyzed by one or more methods speC1fic for die assay to determine phenotypic outcomes and endpoints. Phenotypic endpoints include changes in cell morphology overT1me or treatment dose as well as changes in levels of cellular components such as proteins, lipids, nucleic aC1ds, hormones, saccharides or metals, Measurements of cellular status which include pH, stage of the cell cycle, intake or excretion of biological indicators by the cell, are also endpoints of interest. Measurement of the expression of one or more of the genes of the cell after treatment is also used as an indicator of the efficacy or potency of the a target inhibitors. Hallmark genes, or those genes suspected to be assoC1ated with a speC1fic disease state, condition, or phenotype, are measured in both treated and untreated cells. In vivo studies The individual subjects of the in vivo studies described herein are warm-blooded vertebrate animals, which includes humans. Example 30 RNA Isolation Poly (A) + mRNA isolation What is Claimed is: 1. A bicyclic nucleoside having the formula: wherein: Bx is a heterocyclic base moiety; T1 is H or a hydroxyl proteC11ng group; T2 is H, a hydroxyl proteC11ng group or a reaC11ve phosphorus group; Z is C1-C6 alkyl, C6-C6 alkenyl, C6-C6 alkynyl, subsT1tuted C1-C6 alkyl, subsT1tuted C6-C6 alkenyl, subsT1tuted C6-C6 alkynyl, acyl, subsT1tuted acyl, subsT1tuted amide, thiol or subsT1tuted thio; and wherein each of the subsT1tuted groups, is, independently, mono or poly subsT1tuted with opT1onally proteC1ed subsT1tuent groups independently seleC1ed from halogen, 0x0, hydroxyl, OJ1, NJ,J2, SJ,, N3, OC(=X)J1, OC(=X)NJ1J2, NJ3C(=X)NJ1J2 and CN, wherein each J1 J2 and J3 is, independently, H or C1-C6 alkyl, and X is O, S or NJ1. 2. The compound of claim 1 wherein Z is C1-C6 alkyl or subsT1tuted C1-C6 alkyl. 3. The compound of claim 2 wherein Z is methyl. 4. The compound of claim 2 wherein Z is subsT1tuted C1-C6 alkyl. 5. The compound of claim 4 wherein said subsT1tuent group is C1-C6 alkoxy. 6. The compound of claim 4 wherein Z is CH3OCH2-. 7. The compound of any one of claims 1 -6 wherein the Z group is in the (i?)- configuraT1on: 8. The compound of any one of claims 1-6 wherein the Z group is in the (5)- configuraT1on; 9. The compound of any one of claims 1-8 wherein at least one of T1 and T2 is a hydroxyl proteC11ng group. 10. The compound of claim 9 wherein each of said hydroxyl proteC11ng groups is, independently, seleC1ed from benzyl, benzoyl, 2,6-dichlorobenzyl, t-butyldimethylsilyl, t-butyl-diphenylsilyl, mesylate, tosylate, dimethoxytrityl (DMT), 9-phenylxanthine-9-yl (Pixyl) and 9-(p-methoxyphenyl)xanthine-9-yl(MOX). 11. The compound of claim 9 wherein T1 is seleC1ed from aC6tyl, benzyl, t-butyldimethy-Isilyl, t-butyldiphenylsilyl and dimethoxytrityl. 12. The compound of claim 11 wherein said T1 is 4,4'-dimethoxytrityl. 13. The compoxmd of any one of claims 1-8 wherein T2 is a reaC11ve phosphorus group, 14. The compound of claim 13 wherein said reaC11ve phosphorus group is diisopropyl-cyanoethoxy phosphoramidite or H-phosphonate. 15. The compound of any one of claims 1-8 wherein T1 is 4,4'-dimethoxytrityl and T2 is diisopropylcyanoethoxy phosphoramidite. 16. An oligomeric compound having at least one monomer of formula: or of formula: wherein Bx is a heterocyclic base moiety;it could T3 is H, a hydroxyl proteC11ng group, a linked conjugate group or an intemucleoside linking group attached to a nucleoside, a nucleoT1de, an oligonucleoside, an oligonucleoT1de, a monomeric subunit or an oligomeric compound; T4 is H, a hydroxyl proteC11ng group, a linked conjugate group or an intemucleoside linking group attached to a nucleoside, a nucleoT1de, an oligonucleoside, an oligonucleoT1de, a monomeric subunit or an oligomeric compound; wherein at least one of T3 and T4 is an intemucleoside linking group attached to a nucleoside, a nucleoT1de, an oligonucleoside, an oligonucleoT1de, a monomeric subunit or an oligomeric compound; and Z is C1-C6 alkyl, C6-C6 alkenyl, C6-C6 alkynyl, subsT1tuted C1-C6 alkyl, subsT1tuted C2-C6 alkenyl, subsT1tuted C2-C6 alkynyl, acyl, subsT1tuted acyl, subsT1tuted amide, thiol or subsT1tuted thio. 17. The oligomeric compound of claim 16 wherein each of the subsT1tuted groups, is, independently, mono or poly subsT1tuted with opT1onally proteC1ed subsT1tuent groups independently seleC1ed from halogen, 0x0, hydroxyl, OJ1, NJ1J2, SJ1, N3, OC(=X)J1, 0C(=X)NJ1J2, NJ3C(=X)NJ1J2 and CN, wherein each J1, J2 and J3 is, independently, H or C1-C6 alkyl, andX is O2 SorNJ1. 18. The oHgomeric compound of claim 16 wherein each Z is, independently, C1-C6 alkyl or subsT1tuted C1-C6 alkyl. 19. The oligomeric compound of claim 18 wherein at least one Z is methyl. 20. The oligomeric compound of claim 18 wherein at least one Z is subsT1tuted C1-C6 alkyl. 21. The oligomeric compound of claim 20 wherein each of said substituent groups is C1-C6 alkoxy. 22. The oligomeric compound of claim 20 wherein at least one Z is CH3OCH2-. 23. The oligomeric compound of any one of claims 16-22 wherein each Z is methyl or I CH3OCH2-. 24. The oligomeric compoumd of any one of claims 16-23 wherein the Z group of at least one monomer of said formula is in the (R)- configuraT1on as represented by formula: 25. The oligomeric compound of claim 24 wherein each Z group of each monomer of said formula is in the {R)- configuraT1on. 26. The oligomeric compound of any one of claims 16-23 wherein the Z group of at least one monomer is in the {S)- configuraT1on as represented by the formula: 27. The oligomeric compound of claim 26 wherein each Z group of each monomer of said formula is in the (S)- configuraT1on. 28. The oligomeric compound of any one of claims 16-27 wherein T3 is H or a hydroxyl proteC11ng group. 29. The oligomeric compound of any one of claims 16-27 wherein T3 is an intemucleoside linking group attached to a nucleoside, a nucleoT1de or a monomeric subunit. 30. The oligomeric compound of any one of claims 16-27 wherein T3 is an intemucleoside linking group attached to an oligonucleoside or an oligonucleoT1de. 31. The oligomeric compound of any one of claims 16-27 wherein T3 is an intemucleoside linking group attached to an oligomeric compound. 32. The oligomeric compound of any one of claims 16-31 wherein T4 is H or a hydroxyl proteC11ng group. 3 3. The oligomeric compound of any one of claims 16-31 wherein T4 is an intemucleoside linking group attached to a nucleoside, a nucleoT1de or a monomeric subunit. 34. The oligomeric compound of any one of claims 16-31 wherein T4 is an intemucleoside linking group attached to an oligonucleoside or an oUgonucleoT1de. 35. The oligomeric compound of any one of claims 16-29 wherein T4 is an intemucleoside linking group attached to an oligomeric compound. 36. The oligomeric compound of any one of claims 16-27 wherein at least one of T3 and T4 comprises an intemucleoside linking group seleC1ed from phosphodiester or phosphorothioate. 37. The oligomeric compound of any one of claims 16-3 6 comprising at least one region of at least two conT1guous monomers of said formula. 38. The oligomeric compound of claim 37 comprising at least two regions of at least two conT1guous monomers of said formula. 39. The oligomeric compound of claim 38 comprising a gapped oligomeric compound. 40. The oligomeric compound of either of claims 37 or 38 further comprising at least one region of from about 8 to about 14 conT1guous fs-D-2'-deoxyribofT1ranosyl nucleosides. 41. The oligomeric compound of claim 40 futher comprising at least one region of from about 9 to about 12 conT1guous 6-D-2'-deoxyribofuranosyl nucleosides. 42. The oligomeric compond of claim 37 comprising one region of from 2 to three conT1guous monomers of said formula, an opT1onal second region of 1 or 2 conT1guous monomers of said formula and a third region of from 8 to 14 C-D-2'-deoxyribofuranosyl nucleosides wherein said third region is loC2ted between said fsrst and said second regions. 43. The oligomeric compond of claim 42 comprising from 8 to 10 fs-D-2'-deoxyribofuranosyl nucleosides. 44. The oligomeric compound of any one of claims 16-43 comprising from about 8 to about 40 nucleosides and/or modifsed nucleosides or mimeT1cs in length. 45. The oligomeric compound of any one of claims 16-43 comprising from about 8 to about 20 nucleosides and/or modifsed nucleosides or mimeT1cs in length. 46. The oligomeric compound of any one of claims 16-43 comprising from about 10 to about 16 nucleosides and/or modifsed nucleosides or mimeT1cs in length. 47. The oligomeric compound of any one of claims 16-43 comprising from about 10 to about 14 nucleosides and/or modifsed nucleosides or mimeT1cs in length. I 48. A method of inhibiT1ng gene expression comprising contaC11ng one or more C6lls, a T1ssue or an animal with an oligomeric compound of any of claims 16 to 45. 49. A compound of any one of claims 16-47, for use in mediC2l therapy. 50. The use of a compound of any one of claims 16-47, for the manufaC1ure of a mediC2ment for inhibiT1ng gene expression.

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