Bicyclic nucleosides and oligomers prepared therefrom

Abstract

The present invention relates to novel bicyclic nucleosides and oligomers prepared therefrom. In particular, the present invention relates to a compound of formula (I), wherein one of T₁ and T₂ is OR₁ or OR₂; and the other of T₁ and T₂ is OR₁ or OR₂; wherein R₁ is H or a hydroxyl protecting group, and R₂ is a phosphorus moiety; and wherein Bx is a nucleobase. Furthermore, the present invention relates to said compounds, bicyclic nucleosides and said oligomers for use as a medicament in the prevention, treatment or diagnosis of a disease.

Description

BICYCLIC NUCLEOSIDES AND OLIGOMERS PREPARED THEREFROM The present invention relates to novel bicyclic nucleosides and oligomers prepared therefrom. In particular, the present invention relates to a compound of formula (I), to an oligomer comprising at least one compound of formula (IV), to the compounds or the oligomer of the invention for use as a medicament in the prevention, treatment or diagnosis of a disease and to a pharmaceutical composition comprising at least one compound or at least one oligomer of the invention. The invention also refers to in vitro uses of the oligomer of the invention for binding to a target nucleic acid sequence and a method for solid-phase synthesis of an oligomer of the invention. RELATED ART Antisense therapy has matured as an important platform for the development of innovative drugs. Oligonucleotide analogs displaying strong and sequence specific binding to single-stranded RNA or double-stranded DNA and exhibiting resistance to enzymatic degradation are potential candidates for therapeutic applications as inhibitors or modulators of protein expression. Chemically modified nucleosides are incorporated into antisense compounds to enhance its properties, such as nuclease resistance, pharmacokinetics or affinity for a target RNA. In the recent years, the field of synthetic biology has evolved with the general aim to develop antisense systems with improved potency and efficacy that do not rely on the known molecular components used in nature. A basic requirement to achieve this goal is the development of artificial genetic polymers, often referred to as xeno-nucleic acids (XNA), that fulfill the function of natural DNA or RNA (Herdewijn et al., Chem. Biodiversity 2009, 6, 791). The availability of such systems and their integration into living organisms is expected to equip them with novel properties that are of interest in the field of biotechnology and medicine. From the vast repertoire of nucleic acid modifications that appeared over the last 30 years, a handful of candidates has been scrutinized towards their suitability as an alternative genetic material. In an attempt to introduce non-natural components into the natural genetic machinery by minimal chemical alteration, it has been shown that thymidine in the genome of E. coli strains can be replaced by 5-chlorouridine in an evolutionary process to a minimum residual thymidine content (Marlière et al., Angewandte Chemie, Int. Edition 2011, 50, 7109). In a different approach, it has been reported that unnatural nucleic acids, such as 1,5- anhydrohexitol nucleic acid (HNA; Hendrix et al., Chem. Eur. J. 1997, 3, 110) and cyclohexene nucleic acid (CeNA; Nauwelaerts et al., Nucleic Acids Res. 2005, 33, 2452), fluoroarabinooligonucleotides (FANA; Wilds et al., J. Nucleic Acids Res. 2000, 28, 3625), arabinonucleic acids (ANA; Damha et al., J. Am. Chem. Soc. 1998, 120, 12976), threose nucleic acid (TNA; Schoning et al., Science 2000, 290, 1347) and locked nucleic acid (LNA; Koshkin et al., J. Am. Chem. Soc. 1998, 120, 13252; Obika et al., Tetrahedron Lett. 1998, 39, 5401) can be transcribed from and reverse transcribed into DNA by DNA-polymerases. In an alternative approach, backbone structure of RNA and DNA has been altered by changing the point of attachment of the internucleosidic phosphate unit to the sugar from the 3' to the 2' oxygen (2',5'-DNA or 2',5'-RNA). While 2',5'-RNA is a naturally occurring biopolymer, first found in bacteria in the form of 2',5' polyadenylates, 2',5'-DNA is artificial (Trujillo et al., Eur. J. Biochem. 1987, 169, 167). The pairing and replication properties of both polymers have been investigated in the past. It was found that 2',5'-RNA binds to complementary RNA but not to DNA. Duplexes with RNA are slightly less stable as compared to pure RNA duplexes and duplexes in the pure 2',5'-RNA series exist but are even less stable (Wasner et al., J. Biochemistry 1998, 37, 7478). In addition, it was shown in primer template extension experiments that stretches of up to four 2',5'-linked nucleotides on a template can be reverse transcribed into DNA with polymerases or reverse transcriptases even though there is no significant affinity of 2',5'-DNA to natural DNA (Sinha et al., J. Am. Chem. Soc. 2004, 126, 40). In order to stabilize complex formation with complementary natural nucleic acids entropically, a bicyclic DNA analog that differs from natural DNA by an additional ethylene bridge located between the centers <com:Math><semantics>C(3′)<annotation encoding="application / x-tex">C(3')< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>C(5′)<annotation encoding="application / x-tex">C(5')< / annotation>< / semantics>< / com:Math> has been designed. The points of attachment of the linking phosphodiester units are the same as in the naturally occurring nucleic acid, i.e. the 3' and 5' terminus. This change in the carbon skeleton results in a locked sugar conformation which causes the bicyclo-deoxynucleosides to exhibit a higher degree of preorganisation of the single strands for duplex formation. Decamers of bicyclo- deoxyadenosine and bicyclo-thymidine bind to their natural RNA and DNA complements as well as with each other, forming double and triple helical structures. Compared with natural DNA, duplex formation is associated with reduced pairing enthalpy and entropy terms, having compensatory effects on the free energy of duplex formation (Bolli et al., Nucleic Acids Res. 1996, 24, 4660). Nevertheless, after more than three decades of research in the antisense field, clinical applications are still limited by the low biostability, the poor pharmacokinetic properties and the off-target toxicity of this class of compounds. Thus, there remains a need for antisense compounds that are resistant to enzymatic degradation in vivo and display strong and sequence specific binding to nucleic acids. SUMMARY OF THE INVENTION In a first aspect, the invention provides a compound of formula (I): [Image disponible dans le document PDF, Image available in the PDF document] (I) wherein one of <com:Math><semantics>T1<annotation encoding="application / x-tex">T_1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>T2<annotation encoding="application / x-tex">T_2< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>OR1<annotation encoding="application / x-tex">OR_1< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>OR2<annotation encoding="application / x-tex">OR_2< / annotation>< / semantics>< / com:Math>; and the other of <com:Math><semantics>T1<annotation encoding="application / x-tex">T_1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>T2<annotation encoding="application / x-tex">T_2< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>OR1<annotation encoding="application / x-tex">OR_1< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>OR2<annotation encoding="application / x-tex">OR_2< / annotation>< / semantics>< / com:Math>; wherein R<com:Sub>1< / com:Sub> is H or a hydroxyl protecting group, and R<com:Sub>2< / com:Sub> is a phosphorus moiety; and wherein Bx is a nucleobase. In a second aspect, the invention provides an oligomer comprising at least one compound of formula (IV) [Image disponible dans le document PDF, Image available in the PDF document] (IV) wherein independently for each of said at least one compound of formula (IV) one of <com:Math><semantics>T3<annotation encoding="application / x-tex">T_3< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>T4<annotation encoding="application / x-tex">T_4< / annotation>< / semantics>< / com:Math> is a nucleosidic linkage group; the other of T<com:Sub>3< / com:Sub> and T<com:Sub>4< / com:Sub> is OR<com:Sub>1< / com:Sub>, OR<com:Sub>2< / com:Sub>, a 5' terminal group, a 7' terminal group or a nucleosidic linkage group, wherein R<com:Sub>1< / com:Sub> is H or a hydroxyl protecting group, and R<com:Sub>2< / com:Sub> is a phosphorus moiety; and Bx is a nucleobase. In a third aspect, the present invention provides for the inventive compound of formula (I), (II) or (III) or the oligomer of the invention for use as a medicament in the prevention or treatment of a disease. In a further aspect, the present invention provides for the oligomer of the invention, preferably the inventive oligomer of the formula (V), for use as a medicament in the prevention, treatment or diagnosis of a disease, wherein said disease is a muscular dystrophy, and wherein preferably said disease is Duchenne muscular dystrophy. In a further aspect, the invention provides a pharmaceutical composition comprising at least one compound selected from formula (I), (II) or (III) or at least one oligomer of the invention. In a further aspect, the oligomer of the invention is used in vitro for binding to a target nucleic acid sequence. In a further aspect, the invention provides a method for solid-phase synthesis of an oligomer of the invention. The invention described herein provides for new compounds, wherein the position of the group used for linkage to other entities, such as the nucleosidic linkage group, is shifted as compared to compounds of the prior art. Thus, the compounds of the invention can be or are linked via the 5' terminus and 7' terminus of its bicyclic sugar to other entities such as nucleosides or nucleotides (FIG. 1C and FIG. 1D). In contrast and in the prior art, nucleosides or nucleotides are linked via the 3' and 5' termini, be it for known nucleosides or nucleotides comprising a bicyclic sugar (FIG. 1B) or as in naturally occurring DNA or RNA (FIG. 1A). As a consequence of that shifted linkage, the backbone geometry of the compounds of the invention within an oligomer is changed. This changed backbone geometry in turn induces a nucleobase stacking of the compounds of the invention that is different from that of naturally occurring nucleic acid helixes. Consequently, oligomers of the invention adopts helix conformations that are distinctly different from that of natural DNA. Furthermore, based on these findings, oligomers of the invention forming duplex structures are expected to have a geometry deviating from conventional canonical duplexes. Despite of the changes in backbone geometry and nucleobase stacking, we have now surprisingly found that oligomers of the invention cross-pair with natural DNA and RNA, and self-duplexes of oligomers of the invention exhibit thermal stabilities that are in the same range as that of natural DNA duplexes. Consequently, the oligomers of the invention have the structural and base-pairing properties necessary to become a novel xeno-nucleic acid that may fulfill the function of natural DNA. Moreover, the oligomers of the invention show comparable base pairing selectivity and have even a better mismatch discrimination ability compared to its natural DNA counterpart. Increasing the mismatch discrimination typically reduces the potential off-target effects and therefore represents an appealing property for an antisense candidate. DESCRIPTION OF FIGURES FIG. 1: A) α-monocyclic DNA; B) bicyclic (bc-)DNA; C) 7',5'-β-bc-DNA, i.e. the inventive compound of formula (III); D) 7',5'-α-bc-DNA, i.e. the inventive compound of formula (II). FIG. 2: Comparison between 7',5'-β-bc-DNA, i.e. the inventive compound of formula (III) depicted on the left side, and 7',5'-<com:Math><semantics>α<annotation encoding="application / x-tex">\alpha< / annotation>< / semantics>< / com:Math>-bc-DNA, i.e. the inventive compound of formula (II) depicted on the right side. FIG. 3: X-ray structure of a) 5'-O-p-nitrobenzoyl-7',5'-α-bc-T, b) 5'-O-acetyl-7',5'-α-bc- GAc. Non-polar hydrogen atoms are omitted for clarity. FIG. 4: Insertion of 7',5'-<com:Math><semantics>α<annotation encoding="application / x-tex">\alpha< / annotation>< / semantics>< / com:Math>-bc-DNA with polarity reversal inside <com:Math><semantics>β<annotation encoding="application / x-tex">\beta< / annotation>< / semantics>< / com:Math>-DNA. FIG. 5: UV-melting curves (260 nm) of oligonucleotide ON21 (SEQ ID NO: 21) with fully modified parallel (oligonucleotide ON22; SEQ ID NO: 22) and antiparallel (oligonucleotide ON23; SEQ ID NO: 23) complement, parallel DNA and parallel RNA, in comparison with the corresponding natural DNA duplex. Total strand concentration: 2 µM in 10 mM NaH<com:Sub>2< / com:Sub>PO<com:Sub>4< / com:Sub>, 150 mM NaCl, pH 7.0. FIG. 6: CD-spectra of duplexes a) DNA·RNA, b) ON21·RNA and c) ON21·DNA d) ON21 ·ON22 at 20 °C. Experimental conditions: Total strand conc. 2µM in 10 mM NaH2PO4, 150 mM NaCl, pH 7.0. FIG. 7: Cropped picture of a gel. a) DNA control experiment. DNA digestion reaction after b) 1 hour c) 2 hours d) 4 hours e) 24 hours; f) control experiment with oligonucleotide ON21; ON21 digestion reaction after g) 1 hour h) 2 hours i) 4 hours j) 24 hours. FIG. 8: Results of C3 complement activation; PO denotes phosphate nucleosidic linkages, PS denotes phosphorothioate nucleosidic linkages, bc-DNA denotes the 7',5'-α-bc- DNA scaffold, tc-DNA denotes the tricyclo scaffold. Each measurement has been repeated at least 3 times. The sequence is similar for the 5 ONs. FIG. 9: Comparison of the mRNA expression level after incubation with PS-<com:Math><semantics>α<annotation encoding="application / x-tex">\alpha< / annotation>< / semantics>< / com:Math>-bc-DNA or PS-tc-DNA. Sequence is similar for the two ONs. Abbreviations as mentioned in FIG. 8. FIG. 10: X-ray structure of 7'-O-p-nitrobenzoyl-7',5'-β-bc-T. Hydrogen atoms are omitted for clarity. FIG. 11: UV-melting curves (260 nm) of the homo 7',5'-β-bc-DNA duplex in comparison with the corresponding natural DNA duplex. Total strand concentration: 2 µM in 10 mM NaH<com:Sub>2< / com:Sub>PO<com:Sub>4< / com:Sub>, 150 mM NaCl, pH 7.0. FIG. 12: CD-spectra of the three duplexes a) ON13·ON14, b) ON13·DNA and c) DNA·DNA at temperatures between 10 and 80 °C. Experimental conditions: Total strand concentration 2 µM in 10 mM NaH<com:Sub>2< / com:Sub>PO<com:Sub>4< / com:Sub>, 1 M NaCl, pH 7.0, 10°C. DETAILED DESCRIPTION OF THE INVENTION Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art to which this invention belongs. The terms "protecting group for an amino", "protecting group for an amino group", or "amino protecting group" as interchangeably used herein, are well known in the art and include those described in detail in Protecting Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, 3<com:Sup>rd< / com:Sup> edition, John Wiley & Sons, 1999, Greene's Protective Groups in Organic Synthesis, P. G. M. Wuts, 5<com:Sup>th< / com:Sup> edition, John Wiley & Sons, 2014, and in Current Protocols in Nucleic Acid Chemistry, edited by S. L. Beaucage et al. 06 / 2012, and hereby in particular in Chapter 2. Suitable "amino protecting groups" for the present invention include and are typically and preferably independently at each occurrence selected from methyl carbamate, ethyl carbamate, 9-fluorenylmethyl carbamate (Fmoc), 9-(2-sulfo)fluorenylmethyl carbamate, 2,7-di-t-butyl-[9-(10,10-dioxo-10,10,10,10-tetrahydrothioxanthyl)]methyl carbamate (DBD-Tmoc), 4-methoxyphenacyl carbamate (Phenoc), 2,2,2-trichloroethyl carbamate (Troc), 2-trimethylsilylethyl carbamate (Teoc), 2-phenylethyl carbamate (hZ), 1,1- dimethyl-2,2-dibromoethyl carbamate (DB-t-BOC), 1,1-dimethyl-2,2,2-trichloroethyl carbamate (TCBOC), benzyl carbamate (Cbz), p-methoxybenzyl carbamate (Moz) and 2,4,6- trimethylbenzyl carbamate; as well as formamide, acetamide, benzamide. The terms "protecting group for a hydroxyl", "protecting group for a hydroxyl group", or "hydroxyl protecting group" as interchangeably used herein, are well known in the art and includes those described in detail in Protecting Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, 3<com:Sup>rd< / com:Sup> edition, John Wiley & Sons, 1999; Greene's Protective Groups in Organic Synthesis, P. G. M. Wuts, 5<com:Sup>th< / com:Sup> edition, John Wiley & Sons, 2014, and in Current Protocols in Nucleic Acid Chemistry, edited by S. L. Beaucage et al. 06 / 2012, and hereby in particular in Chapter 2. In a certain embodiment, the "hydroxyl protecting groups" of the present invention include and, typically and preferably are independently at each occurrence selected from, acetyl, benzoyl, benzyl, β-methoxyethoxymethyl ether (MEM), dimethoxytrityl, [bis-(4-methoxyphenyl)phenylmethyl] (DMTr), methoxymethyl ether (MOM), methoxytrityl [(4-methoxyphenyl)diphenylmethyl] (MMT), p-methoxybenzyl ether (PMB), methylthiomethyl ether, pivaloyl (Piv), tetrahydropyranyl (THP), tetrahydrofuran (THF), trityl (triphenylmethyl, Tr), silyl ether, such as t-Butyldiphenylsilyl ether (TBDPS), trimethylsilyl (TMS), tert-butyldimethylsilyl (TBDMS), tri-iso-propylsilyloxymethyl (TOM), and triisopropylsilyl (TIPS) ethers; methyl ethers, ethoxyethyl ethers (EE). In a preferred embodiment, the "hydroxyl protecting groups" of the present invention include and, typically and preferably are independently at each occurrence selected from, acetyl, t-butyl, t-butoxymethyl, methoxymethyl, tetrahydropyranyl, 1-ethoxyethyl, 1-(2- chloroethoxy)ethyl, 2-trimethylsilylethyl, p-chlorophenyl, 2,4-dinitrophenyl, benzyl, benzyl, p-phenylbenzoyl, 2,6-dichlorobenzyl, diphenylmethyl, p-nitrobenzyl, triphenylmethyl (trityl), 4,4'-dimethoxytrityl, trimethylsilyl, triethylsilyl, t-butyldimethylsilyl (TBDMS), t- butyldiphenylsilyl (TBDPS), triphenylsilyl, triisopropylsilyl, benzoylformate, chloroacetyl, trichloroacetyl, trifiuoroacetyl, pivaloyl, 9-fluorenylmethyl carbonate, mesylate, tosylate, triflate, 4-monomethoxytrityl (MMTr), 4,4'dimethoxytrityl, (DMTr) and 4,4',4"- trimethoxytrityl (TMTr), 2-cyanoethyl (CE or Cne), 2-(trimethylsilyl)ethyl (TSE), 2-(2- nitrophenyl)ethyl, 2-(4-cyanophenyl)ethyl 2-(4- nitrophenyl)ethyl (NPE), 2-(4- nitrophenylsulfonyl)ethyl, 3,5-dichlorophenyl, 2,4-dimethylphenyl, 2-nitrophenyl, 4- nitrophenyl, 2,4,6-trimethylphenyl, 2-(2-nitrophenyl)ethyl, butylthiocarbonyl, 4,4',4"- tris(benzoyloxy)trityl, diphenylcarbamoyl, levulinyl, 2-( dibromomethyl)benzoyl (Dbmb), 2- (isopropylthiomethoxymethyl)benzoyl (Ptmt), 9- phenylxanthen-9-yl (pixyl) or 9-(p- methoxyphenyl)xanthine-9-y 1 (MOX). In some embodiments, the hydroxyl protecting group is independently at each occurrence selected from acetyl, benzyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, trityl, 4- monomethoxytrityl, 4,4'-dimethoxytrityl (DMTr), 4,4',4"-trimethoxytrityl (TMTr), 9- phenylxanthin-9-yl (Pixyl) and 9-(p-methoxyphenyl)xanthin-9-yl (MOX). In preferred embodiments, the hydroxyl protecting group is independently at each occurrence selected from triphenylmethyl (trityl), 4-monomethoxytrityl, 4,4'-dimethoxytrityl (DMTr), 4,4',4"- trimethoxytrityl (TMTr), 9-phenylxanthin-9-yl (Pixyl) and 9-(p-methoxyphenyl)xanthin-9-yl (MOX). In further preferred embodiments, the hydroxyl protecting group is independently at each occurrence selected from trityl, 4-monomethoxytrityl and 4,4'-dimethoxytrityl group. In a very preferred embodiment, said hydroxyl protecting group is independently at each occurrence selected from triphenylmethyl (trityl), 4-monomethoxytrityl, 4,4'-dimethoxytrityl (DMTr), 4,4',4"-trimethoxytrityl (TMTr), 9-phenylxanthin-9-yl (Pixyl) and 9-(p- methoxyphenyl)xanthin-9-yl (MOX). In a more preferred embodiment, the hydroxyl protecting groups of the present invention is acetyl, dimethoxytrityl (DMTr), tert- butyldimethylsilyl (TBDMS), tri-iso-propylsilyloxymethyl (TOM), or t-butyldiphenylsilyl ether (TBDPS). In an again very preferred embodiment, said hydroxyl protecting group is independently at each occurrence selected from 4,4'-dimethoxytrityl (DMTr) or 4- monomethoxytrityl. In an again further very preferred embodiment, said hydroxyl protecting group is 4, 4'-dimethoxytrityl (DMTr). The term "phosphorus moiety", as used herein, refers to a moiety comprising a phosphorus atom in the P<com:Sup>III< / com:Sup> or P<com:Sup>V< / com:Sup> valence state and which is represented by formula (VII) [Image disponible dans le document PDF, Image available in the PDF document] (VII), wherein W represents O, S or Se or W represents an electron pair; R<com:Sub>3< / com:Sub> and R<com:Sub>4< / com:Sub> are independently of each other H, halogen, OH, OR<com:Sub>5< / com:Sub>, NR<com:Sub>6< / com:Sub>R<com:Sub>7< / com:Sub>, SH, SR<com:Sub>8< / com:Sub>, C<com:Sub>1< / com:Sub>- C<com:Sub>6< / com:Sub>alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkoxy, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>haloalkoxy, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>aminoalkyl; wherein R<com:Sub>5< / com:Sub> is C<com:Sub>1< / com:Sub>- C<com:Sub>9< / com:Sub>alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkoxy, each independently of each other optionally substituted with cyano, nitro, halogen, -NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl, -NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkylsulfonyl; aryl, C<com:Sub>1< / com:Sub>- C<com:Sub>6< / com:Sub>alkylenearyl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkylenediaryl, each independently of each other optionally substituted with cyano, nitro, halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkoxy, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>haloalkoxy, NHC(O)C<com:Sub>1< / com:Sub>- C<com:Sub>3< / com:Sub>alkyl, NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkylsulfonyl; acetyl; a hydroxyl protecting group; wherein R<com:Sub>6< / com:Sub> and R<com:Sub>7< / com:Sub> are independently of each other hydrogen, C<com:Sub>1< / com:Sub>-C<com:Sub>9< / com:Sub>alkyl optionally substituted with cyano, nitro, halogen, C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, C<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkoxy; aryl optionally substituted with cyano, nitro, halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkoxy; an amino protecting group; or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein preferably said heterocyclic ring is selected from pyrollidinyl, piperidinyl, morpholinyl, piperazinyl and homopiperazine, wherein said heterocyclic ring is optionally substituted with <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math> alkyl; and wherein <com:Math><semantics>R8<annotation encoding="application / x-tex">R_8< / annotation>< / semantics>< / com:Math> is a thiol protecting group; and wherein the wavy line indicates the attachment to the oxygen of said OR<com:Sub>2< / com:Sub> group. When W represents O, S or Se then said P atom within said phosphorus moiety is in its P<com:Sup>V< / com:Sup> valence state. When W represents an electron pair then said P atom within said phosphorus moiety is in its P<com:Sup>III< / com:Sup> valence. The moiety of formula (VII) includes any possible stereoisomer. Further included in said moieties represented by formula (VII) are salts thereof, wherein typically and preferably said salts are formed upon treatment with inorganic bases or amines, and are typically and preferably salts derived from reaction with the OH or SH groups being (independently of each other) said R<com:Sub>3< / com:Sub> and R<com:Sub>4< / com:Sub>. Preferred inorganic bases or amines leading to said salt formation with the OH or SH groups are well known in the art and are typically and preferably trimethylamine, diethylamine, methylamine or ammonium hydroxide. These phosphorus moieties included in the present invention are, if appropriate, also abbreviated as "O'HB<com:Sup>+< / com:Sup>", wherein said HB<com:Sup>+< / com:Sup> refers to the counter cation formed. In a preferred embodiment, in the "phosphorus moiety", R<com:Sub>3< / com:Sub> and R<com:Sub>4< / com:Sub> are independently of each other H, OH, OR<com:Sub>5< / com:Sub>, NR<com:Sub>6< / com:Sub>R<com:Sub>7< / com:Sub>, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkoxy, C<com:Sub>1< / com:Sub>- C<com:Sub>6< / com:Sub>haloalkoxy, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>aminoalkyl; wherein R<com:Sub>5< / com:Sub> is C<com:Sub>1< / com:Sub>-C<com:Sub>9< / com:Sub>alkyl optionally substituted with cyano, nitro, halogen; aryl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkylenearyl, each independently of each other optionally substituted with cyano, nitro, halogen; acetyl; a hydroxyl protecting group; wherein R<com:Sub>6< / com:Sub> and R<com:Sub>7< / com:Sub> are independently of each other hydrogen, C<com:Sub>1< / com:Sub>-C<com:Sub>9< / com:Sub>alkyl optionally substituted with cyano, nitro, halogen; aryl optionally substituted with cyano, nitro, halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub> alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkoxy; an amino protecting group; and wherein R<com:Sub>8< / com:Sub> is a thiol protecting group; and wherein the wavy line indicates the attachment to the oxygen of said OR<com:Sub>2< / com:Sub> group. The term "phosphorus moiety", as used herein, includes and, typically and preferably is independently at each occurrence selected from a moiety derived from phosphonates, phosphite triester, monophosphate, diphosphate, triphosphate, phosphate triester, phosphate diester, thiophosphate ester, di-thiophosphate ester or phosphoramidites. Thus, in a preferred embodiment, said OR<com:Sub>2< / com:Sub> is independently at each occurrence selected from phosphonates, phosphite triester, monophosphate, diphosphate, triphosphate, phosphate triester, phosphate diester, thiophosphate ester, di-thiophosphate ester or phosphoramidites, and wherein preferably said OR<com:Sub>2< / com:Sub> is a phosphoramidite or a phosphate triester, more preferably a phosphoramidite. In a preferred embodiment, the phosphorus moiety is derived from a phosphonate represented by formula (VII), wherein W is O, R<com:Sub>3< / com:Sub> is selected from C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, C<com:Sub>1< / com:Sub>- C<com:Sub>6< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkoxy, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>haloalkoxy, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>aminoalkyl, and R<com:Sub>4< / com:Sub> is OH or O<com:Sup>+< / com:Sup>HB<com:Sup>+< / com:Sup>; and wherein the wavy line indicates the attachment to the oxygen of said OR<com:Sub>2< / com:Sub> group. In another embodiment, the phosphorus moiety of formula (VII) is an H-phosphonate, wherein W is O, R<com:Sub>3< / com:Sub> is hydrogen and R<com:Sub>4< / com:Sub> is OH or O<com:Sup>-< / com:Sup>HB<com:Sup>+< / com:Sup>; and wherein preferably said O<com:Sup>-< / com:Sup>HB<com:Sup>+< / com:Sup> is HNEt<com:Sub>3< / com:Sub><com:Sup>+< / com:Sup>. In a further embodiment, the phosphorus moiety of formula (VII) is an alkyl-phosphonate, wherein W is O, R<com:Sub>3< / com:Sub> is alkyl, and R<com:Sub>4< / com:Sub> is OH or O<com:Sup>-< / com:Sup>HB<com:Sup>+< / com:Sup>; and wherein preferably said O<com:Sup>-< / com:Sup>HB<com:Sup>+< / com:Sup> is HNEt<com:Sub>3< / com:Sub><com:Sup>+< / com:Sup>. More preferably, the phosphorus moiety of formula (VII) is methyl-phosphonate, wherein W is O, R<com:Sub>3< / com:Sub> is hydrogen and R<com:Sub>4< / com:Sub> is OH or O HB<com:Sup>+< / com:Sup>; and wherein preferably said O HB<com:Sup>+< / com:Sup> is HNEt<com:Sub>3< / com:Sub><com:Sup>+< / com:Sup>). In another embodiment, the phosphorus moiety of formula (VII) is a phosphonocarboxylate, wherein R<com:Sub>3< / com:Sub> or R<com:Sub>4< / com:Sub> are independently of each other a carboxylic acid. Preferably, said phosphonocarboxylate is phosphonoacetic acid or phosphonoformic acid. In a further embodiment, the phosphorus moiety of formula (VII) is a 2-aminoethyl-phosphonate. In a preferred embodiment, R<com:Sub>3< / com:Sub> and R<com:Sub>4< / com:Sub> of the phosphorus moiety of formula (VII) are independently of each other H, OH, halogen, OR<com:Sub>5< / com:Sub>, NR<com:Sub>6< / com:Sub>R<com:Sub>7< / com:Sub>, SH, SR<com:Sub>8< / com:Sub>, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkyl, preferably C<com:Sub>1< / com:Sub>-C<com:Sub>2< / com:Sub>alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>haloalkyl, preferably C<com:Sub>1< / com:Sub>-C<com:Sub>2< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkoxy, preferably C<com:Sub>1< / com:Sub>-C<com:Sub>2< / com:Sub>alkoxy, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C4<annotation encoding="application / x-tex">C_4< / annotation>< / semantics>< / com:Math>haloalkoxy, preferably <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>haloalkoxy, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C4<annotation encoding="application / x-tex">C_4< / annotation>< / semantics>< / com:Math>aminoalkyl, preferably <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>aminoalkyl; and wherein R<com:Sub>5< / com:Sub> is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, preferably C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl, each independently of each other optionally substituted with cyano, nitro, halogen, NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl, NHC(O)C<com:Sub>1< / com:Sub>- <com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>haloalkyl, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>alkylsulfonyl; aryl, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>alkylenearyl, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>alkylenediaryl, each independently of each other optionally substituted with cyano, nitro, halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkoxy, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>haloalkoxy, NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl, NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>- C<com:Sub>3< / com:Sub>alkylsulfonyl; acetyl; a hydroxyl protecting group; and wherein R<com:Sub>6< / com:Sub> and R<com:Sub>7< / com:Sub> are independently of each other hydrogen, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, preferably C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkyl, each independently of each other optionally substituted with cyano, nitro, halogen, C<com:Sub>2< / com:Sub>-C<com:Sub>4< / com:Sub>alkenyl, C<com:Sub>3< / com:Sub>- C<com:Sub>6< / com:Sub>cycloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkoxy; aryl optionally substituted with cyano, nitro, halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub> alkyl, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>alkoxy; an amino protecting group; or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein preferably said heterocyclic ring is selected from pyrollidinyl, piperidinyl, morpholinyl, piperazinyl and homopiperazine, wherein said heterocyclic ring is optionally substituted with <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math> alkyl; and wherein <com:Math><semantics>R8<annotation encoding="application / x-tex">R_8< / annotation>< / semantics>< / com:Math> is a thiol protecting group; and wherein the wavy line indicates the attachment to the oxygen of said OR<com:Sub>2< / com:Sub> group. In another preferred embodiment, R<com:Sub>3< / com:Sub> or R<com:Sub>4< / com:Sub> of the phosphorus moiety of formula (VII) is independently at each occurrence and of each other halogen, preferably chlorine, or OR<com:Sub>5< / com:Sub>, wherein R<com:Sub>5< / com:Sub> is a hydroxyl protecting group. Additional phosphorus moieties used in the invention are disclosed in Tetrahedron Report Number 309 (Beaucage and Iyer, Tetrahedron, 1992, 48, 2223-2311). The term "phosphorus moiety", as used herein, preferably refers to a group R<com:Sub>2< / com:Sub> comprising a phosphorus atom in the P<com:Sup>III< / com:Sup> or P<com:Sup>V< / com:Sup> valence state and which is represented independently at each occurrence either by formula (VIII), formula (IX) or formula (X), [Image disponible dans le document PDF, Image available in the PDF document] wherein Y is O, S or Se, and wherein Y preferably is O or S, more preferably Y is O; and wherein R<com:Sub>5< / com:Sub> and R<com:Sub>5< / com:Sub>, are independently at each occurrence and of each other hydrogen, C<com:Sub>1< / com:Sub>- C<com:Sub>9< / com:Sub>alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkoxy, each independently of each other optionally substituted with cyano, nitro, halogen, -NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl, -NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkylsulfonyl; aryl, C<com:Sub>1< / com:Sub>- C<com:Sub>6< / com:Sub>alkylenearyl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkylenediaryl each independently of each other optionally substituted with cyano, nitro, halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkoxy, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>haloalkoxy, -NHC(O)C<com:Sub>1< / com:Sub>- C<com:Sub>3< / com:Sub>alkyl, NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkylsulfonyl; a hydroxyl protecting group; wherein <com:Math><semantics>R6<annotation encoding="application / x-tex">R_6< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R7<annotation encoding="application / x-tex">R_7< / annotation>< / semantics>< / com:Math> are independently of each other hydrogen, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C9<annotation encoding="application / x-tex">C_9< / annotation>< / semantics>< / com:Math>alkyl optionally substituted with cyano, nitro, halogen, C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, C<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkoxy; aryl, preferably phenyl, optionally substituted with cyano, nitro, halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub> alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub> alkoxy; an amino protecting group; or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein preferably said heterocyclic ring is selected from pyrollidinyl, piperidinyl, morpholinyl, piperazinyl and homopiperazine, wherein said heterocyclic ring is optionally substituted with <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math> alkyl; and wherein <com:Math><semantics>R8<annotation encoding="application / x-tex">R_8< / annotation>< / semantics>< / com:Math> is a thiol protecting group; and wherein the wavy line indicates the attachment to the oxygen of said OR<com:Sub>2< / com:Sub> group. In a preferred embodiment, said phosphorus moiety R<com:Sub>2< / com:Sub> is represented by formula (VIII) [Image disponible dans le document PDF, Image available in the PDF document] wherein Y is O, S or Se, wherein Y preferably is O or S, most preferably Y is O; and wherein <com:Math><semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R5′<annotation encoding="application / x-tex">R_{5'}< / annotation>< / semantics>< / com:Math> are independently at each occurrence and of each other hydrogen, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>- C<com:Sub>9< / com:Sub>alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkoxy, each independently of each other optionally substituted with cyano, nitro, halogen, -NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl, -NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkylsulfonyl; aryl, C<com:Sub>1< / com:Sub>- C<com:Sub>6< / com:Sub>alkylenearyl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkylenediaryl each independently of each other optionally substituted with cyano, nitro, halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkoxy, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>haloalkoxy, -NHC(O)C<com:Sub>1< / com:Sub>- C<com:Sub>3< / com:Sub>alkyl, NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkylsulfonyl; a hydroxyl protecting group; <com:Math><semantics>P(O)(OR9)(OR9′)<annotation encoding="application / x-tex">P(O)(OR_9)(OR_{9'})< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>P(O)OP(O)(OR9)(OR9′)<annotation encoding="application / x-tex">P(O)OP(O)(OR_9)(OR_{9'})< / annotation>< / semantics>< / com:Math>; wherein <com:Math><semantics>R9<annotation encoding="application / x-tex">R_9< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R9′<annotation encoding="application / x-tex">R_{9'}< / annotation>< / semantics>< / com:Math> are independently at each occurrence and of each other hydrogen, C<com:Sub>1< / com:Sub>-C<com:Sub>9< / com:Sub>alkyl optionally substituted with cyano, nitro, halogen, <com:Math><semantics>−NHC(O)C1−C3<annotation encoding="application / x-tex">-NHC(O)C_1-C_3< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−NHC(O)C1−C3<annotation encoding="application / x-tex">-NHC(O)C_1-C_3< / annotation>< / semantics>< / com:Math>haloalkyl, <com:Math><semantics>C1−C3<annotation encoding="application / x-tex">C_1-C_3< / annotation>< / semantics>< / com:Math>alkylsulfonyl; aryl, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>- C<com:Sub>6< / com:Sub>alkylenearyl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkylenediaryl each independently of each other optionally substituted with cyano, nitro, halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkoxy, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>haloalkoxy, -NHC(O)C<com:Sub>1< / com:Sub>- C<com:Sub>3< / com:Sub>alkyl, NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkylsulfonyl; a hydroxyl protecting group; and wherein the wavy line indicates the attachment to the oxygen of said OR<com:Sub>2< / com:Sub> group. In a preferred embodiment, R<com:Sub>5< / com:Sub> and R<com:Sub>5< / com:Sub>, of formula (VIII) are independently at each occurrence and of each other hydrogen, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, preferably <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C4<annotation encoding="application / x-tex">C_4< / annotation>< / semantics>< / com:Math>alkoxy, preferably <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>alkoxy, each independently of each other optionally substituted with cyano, nitro, halogen, -NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl, -NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkylsulfonyl; aryl, preferably phenyl, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkylenearyl, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkylenediaryl each independently of each other optionally substituted with cyano, nitro, halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkoxy, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>- C<com:Sub>4< / com:Sub>haloalkoxy, -NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl, NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkylsulfonyl; a hydroxyl protecting group. In a preferred embodiment, <com:Math><semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics>< / com:Math>, of formula (VIII) are independently of each other C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkyl or aryl, preferably phenyl. In another preferred embodiment, R<com:Sub>5< / com:Sub> and R<com:Sub>5< / com:Sub>, of formula (VIII) are independently of each other methyl or ethyl. In a further preferred embodiment, R<com:Sub>5< / com:Sub> and R<com:Sub>5< / com:Sub>, of formula (VIII) are independently of each other phenyl or benzyl. In another preferred embodiment, R<com:Sub>5< / com:Sub> and R<com:Sub>5< / com:Sub>, are independently at each occurrence and of each other hydrogen or a hydroxyl protecting group, preferably a hydroxyl protecting group. In a preferred embodiment, in formula (VIII), <com:Math><semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R5<annotation encoding="application / x-tex">R_{5}< / annotation>< / semantics>< / com:Math>, are independently at each occurrence and of each other hydrogen, C<com:Sub>1< / com:Sub>-C<com:Sub>9< / com:Sub>alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkoxy, each independently of each other optionally substituted with cyano, nitro, halogen; aryl, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkylenearyl, each independently of each other optionally substituted with cyano, nitro, halogen; or a hydroxyl protecting group. Typically and preferably, said phosphorus moiety R<com:Sub>2< / com:Sub> represented by formula (VIII) is herein referred as "phosphate moiety". In a preferred embodiment, said phosphorus moiety R<com:Sub>2< / com:Sub> is represented by formula (IX) [Image disponible dans le document PDF, Image available in the PDF document] (IX), wherein wherein Y is O, S or Se, and wherein Y preferably is O or S, most preferably Y is O; and wherein R<com:Sub>5< / com:Sub> is independently at each occurrence hydrogen, C<com:Sub>1< / com:Sub>-C<com:Sub>9< / com:Sub>alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkoxy, each independently of each other optionally substituted with cyano, nitro, halogen, -NHC(O)C<com:Sub>1< / com:Sub>- C<com:Sub>3< / com:Sub>alkyl, -NHC(O)<com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>haloalkyl, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>alkylsulfonyl; aryl, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkylenearyl, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>- C<com:Sub>6< / com:Sub>alkylenediaryl each independently of each other optionally substituted with cyano, nitro, halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkoxy, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>haloalkoxy, -NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl, NHC(O)C<com:Sub>1< / com:Sub>- C<com:Sub>3< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkylsulfonyl; a hydroxyl protecting group; wherein R<com:Sub>6< / com:Sub> and R<com:Sub>7< / com:Sub> are independently of each other hydrogen, C<com:Sub>1< / com:Sub>-C<com:Sub>9< / com:Sub>alkyl optionally substituted with cyano, nitro, halogen, C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, C<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkoxy; aryl, preferably phenyl, optionally substituted with cyano, nitro, halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub> alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkoxy; an amino protecting group; or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein preferably said heterocyclic ring is selected from pyrollidinyl, piperidinyl, morpholinyl, piperazinyl and homopiperazine, wherein said heterocyclic ring is optionally substituted with <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math> alkyl; and wherein the wavy line indicates the attachment to the oxygen of said OR<com:Sub>2< / com:Sub> group. Typically and preferably, said phosphorus moiety R<com:Sub>2< / com:Sub> represented by formula (IX) is referred herein as "phosphoramidate moiety" or, interchangeably used, "phosphoroamidate moiety". In a preferred embodiment, said phosphorus moiety R<com:Sub>2< / com:Sub> is represented by formula (X) [Image disponible dans le document PDF, Image available in the PDF document] (X), wherein R<com:Sub>5< / com:Sub> is hydrogen, C<com:Sub>1< / com:Sub>-C<com:Sub>9< / com:Sub>alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkoxy, each independently of each other optionally substituted with cyano, nitro, halogen, -NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl, -NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>- C<com:Sub>3< / com:Sub>alkylsulfonyl; aryl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkylenearyl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkylenediaryl independently of each other optionally substituted with cyano, nitro, halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkoxy, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>- C<com:Sub>4< / com:Sub>haloalkoxy, -NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl, NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkylsulfonyl, a hydroxyl protecting group; and wherein R<com:Sub>6< / com:Sub> and R<com:Sub>7< / com:Sub> are independently of each other hydrogen, C<com:Sub>1< / com:Sub>-C<com:Sub>9< / com:Sub>alkyl optionally substituted with cyano, nitro, halogen, C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, C<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkoxy, aryl, preferably phenyl, optionally substituted with cyano, nitro, halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub> alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkoxy; or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein preferably said heterocyclic ring is selected from pyrollidinyl, piperidinyl, morpholinyl, piperazinyl and homopiperazine, wherein said heterocyclic ring is optionally substituted with <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math> alkyl, and wherein the wavy line indicates the attachment to the oxygen of said <com:Math><semantics>OR2<annotation encoding="application / x-tex">OR_2< / annotation>< / semantics>< / com:Math> group. Typically and preferably, said phosphorus moiety R<com:Sub>2< / com:Sub> represented by formula (X) is referred herein as "phosphoramidite moiety" or, interchangeably used, "phosphoroamidite moiety". In a preferred embodiment, in formula (IX) said Y is O; said R<com:Sub>5< / com:Sub> is independently at each occurrence hydrogen, C<com:Sub>1< / com:Sub>-C<com:Sub>9< / com:Sub>alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkoxy, each independently of each other optionally substituted with cyano, nitro, halogen; aryl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkylenearyl, each independently of each other optionally substituted with cyano, nitro, halogen; a hydroxyl protecting group; wherein R<com:Sub>6< / com:Sub> and R<com:Sub>7< / com:Sub> are independently of each other hydrogen, C<com:Sub>1< / com:Sub>-C<com:Sub>9< / com:Sub>alkyl optionally substituted with cyano, nitro, halogen, C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl; aryl optionally substituted with cyano, nitro, halogen, C<com:Sub>1< / com:Sub>- C<com:Sub>3< / com:Sub> alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkoxy; an amino protecting group; and wherein the wavy line indicates the attachment to the oxygen of said OR<com:Sub>2< / com:Sub> group. In a preferred embodiment, in formula (X) said R<com:Sub>5< / com:Sub> is independently at each occurrence hydrogen, C<com:Sub>1< / com:Sub>-C<com:Sub>9< / com:Sub>alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkoxy, each independently of each other optionally substituted with cyano, nitro, halogen; aryl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkylenearyl, each independently of each other optionally substituted with cyano, nitro, halogen; a hydroxyl protecting group; wherein R<com:Sub>6< / com:Sub> and R<com:Sub>7< / com:Sub> are independently of each other hydrogen, C<com:Sub>1< / com:Sub>-C<com:Sub>9< / com:Sub>alkyl optionally substituted with cyano, nitro, halogen, C2-C6alkenyl; aryl optionally substituted with cyano, nitro, halogen, C1-C3 alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkoxy; an amino protecting group; and wherein the wavy line indicates the attachment to the oxygen of said OR<com:Sub>2< / com:Sub> group. In a very preferred embodiment, said phosphorus moiety R<com:Sub>2< / com:Sub> is independently at each occurrence selected from a phosphate moiety, phosphoramidate moiety and phosphoramidite moiety. In a further preferred embodiment, said R<com:Sub>5< / com:Sub> is independently at each occurrence hydrogen, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, preferably C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkoxy, each independently of each other optionally substituted with cyano, nitro, halogen, -NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl, -NHC(O)C<com:Sub>1< / com:Sub>- C<com:Sub>3< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkylsulfonyl; aryl, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkylenearyl, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkylenediaryl each independently of each other optionally substituted with cyano, nitro, halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkoxy, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>haloalkoxy, -NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl, NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>- C<com:Sub>3< / com:Sub>alkylsulfonyl; a hydroxyl protecting group; wherein R<com:Sub>6< / com:Sub> and R<com:Sub>7< / com:Sub> are independently of each other hydrogen, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl optionally substituted with cyano, nitro, halogen, C<com:Sub>2< / com:Sub>-C<com:Sub>4< / com:Sub>alkenyl, C<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkoxy; aryl optionally substituted with cyano, nitro, halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub> alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkoxy; an amino protecting group; or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein preferably said heterocyclic ring is selected from pyrollidinyl, piperidinyl, morpholinyl, piperazinyl and homopiperazine, wherein said heterocyclic ring is optionally substituted with C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub> alkyl; and wherein the wavy line indicates the attachment to the oxygen of said OR<com:Sub>2< / com:Sub> group. In a further preferred embodiment, said R<com:Sub>5< / com:Sub> is C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl optionally substituted with cyano, chlorine, fluorine or bromine; aryl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkylenearyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkylenediaryl, each independently of each other optionally substituted with cyano, nitro, chlorine, fluorine, bromine, C<com:Sub>1< / com:Sub>-C<com:Sub>2< / com:Sub>alkoxy, C<com:Sub>1< / com:Sub>haloalkyl. In a more preferred embodiment, said R<com:Sub>5< / com:Sub> is a C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl optionally and preferably substituted with cyano, chlorine, fluorine or bromine; preferably substituted with cyano. In again a more preferred embodiment, said R<com:Sub>5< / com:Sub> is a cyano substituted C<com:Sub>2< / com:Sub>alkyl, preferably said R<com:Sub>5< / com:Sub> is -CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>-CN. In a further preferred embodiment, said <com:Math><semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C4<annotation encoding="application / x-tex">C_4< / annotation>< / semantics>< / com:Math>alkyl, preferably methyl or ethyl; aryl, preferably phenyl or benzyl; chloride or a hydroxyl protecting group. In a further preferred embodiment, said R<com:Sub>5< / com:Sub> is methyl or a hydroxyl protecting group. In a further preferred embodiment, said R<com:Sub>5< / com:Sub> is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkoxy optionally substituted with cyano, chlorine, fluorine or bromine. In a further preferred embodiment, said R<com:Sub>6< / com:Sub> and R<com:Sub>7< / com:Sub> are independently of each other H or C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl; or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein said heterocyclic ring is selected from pyrollidinyl, piperidinyl, morpholinyl, piperazinyl wherein said heterocyclic ring is optionally substituted with methyl. In a further preferred embodiment, said R<com:Sub>6< / com:Sub> and R<com:Sub>7< / com:Sub> are independently of each other C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl, alkoxy or aryl, wherein the aryl is preferably phenyl or benzyl, optionally substituted with cyano, nitro, chlorine, fluorine, bromine. In a further preferred embodiment, said R<com:Sub>6< / com:Sub> is hydrogen, and R<com:Sub>7< / com:Sub> is (i) C<com:Sub>1< / com:Sub>-C<com:Sub>9< / com:Sub>alkyl or (ii) aryl, (i) or (ii) optionally substituted with cyano, nitro, halogen, aryl, wherein preferably <com:Math><semantics>R7<annotation encoding="application / x-tex">R_7< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>alkyl, phenyl or benzyl. In a further preferred embodiment, said R<com:Sub>6< / com:Sub> and R<com:Sub>7< / com:Sub> are independently of each other selected from methyl, ethyl, isopropyl or isobutyl. In a more preferred embodiment, said R<com:Sub>6< / com:Sub> and <com:Math><semantics>R7<annotation encoding="application / x-tex">R_7< / annotation>< / semantics>< / com:Math> are independently of each other isopropyl. In another very preferred embodiment, said phosphorus moiety R<com:Sub>2< / com:Sub> is represented by formula (X), wherein said R<com:Sub>5< / com:Sub> is (i) C<com:Sub>1< / com:Sub>-C<com:Sub>9< / com:Sub>alkyl; (ii) aryl, preferably phenyl; or (iii) said (i) or said (ii) optionally substituted with cyano, nitro, halogen, aryl; and wherein said R<com:Sub>6< / com:Sub> and R<com:Sub>7< / com:Sub> are independently of each other <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C9<annotation encoding="application / x-tex">C_9< / annotation>< / semantics>< / com:Math>alkyl, preferably isopropyl. In another very preferred embodiment, said phosphorus moiety R<com:Sub>2< / com:Sub> is represented by formula (X), wherein R<com:Sub>5< / com:Sub> is C<com:Sub>1< / com:Sub>-C<com:Sub>9< / com:Sub>alkyl optionally substituted with cyano, nitro, halogen, - NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl, -NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkylsulfonyl; aryl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkylenearyl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkylenediaryl independently of each other optionally substituted with cyano, nitro, halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkoxy, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>haloalkoxy, -NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl, -NHC(O)C<com:Sub>1< / com:Sub>- C<com:Sub>3< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkylsulfonyl; and R<com:Sub>6< / com:Sub> and R<com:Sub>7< / com:Sub> are independently of each other C<com:Sub>1< / com:Sub>-C<com:Sub>9< / com:Sub>alkyl optionally substituted with cyano, nitro, halogen, C2-C6alkenyl, C3-C6cycloalkyl, C1- C<com:Sub>3< / com:Sub>alkoxy, phenyl optionally substituted with cyano, nitro, halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub> alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkoxy; or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein preferably said heterocyclic ring is selected from pyrollidinyl, piperidinyl, morpholinyl, piperazinyl and homopiperazine, wherein said heterocyclic ring is optionally substituted with C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub> alkyl; and wherein the wavy line indicates the attachment to the oxygen of said OR<com:Sub>2< / com:Sub> group. In another very preferred embodiment, said phosphorus moiety R<com:Sub>2< / com:Sub> is represented by formula (X), wherein said R<com:Sub>5< / com:Sub> is C<com:Sub>1< / com:Sub>-C<com:Sub>9< / com:Sub>alkyl optionally substituted with cyano, nitro, chlorine, fluorine, bromine, -NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl, -NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>haloalkyl; aryl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkylenearyl, C<com:Sub>1< / com:Sub>- C<com:Sub>6< / com:Sub>alkylenediaryl independently of each other optionally substituted with cyano, nitro, chlorine, fluorine, bromine, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkoxy, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>haloalkyl. In another very preferred embodiment, said phosphorus moiety R<com:Sub>2< / com:Sub> is represented by formula (X), wherein said <com:Math><semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>alkyl optionally substituted with cyano, chlorine, fluorine and bromine; aryl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkylenearyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkylenediaryl, independently of each other optionally substituted with cyano, nitro, chlorine, fluorine, bromine, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>alkoxy, C<com:Sub>1< / com:Sub>haloalkyl. In another very preferred embodiment, said phosphorus moiety R<com:Sub>2< / com:Sub> is represented by formula (X), wherein said R<com:Sub>5< / com:Sub> is C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl, 2-cyanoethyl, 2,2,2-trichloroethyl, 2,2,2- tribromoethyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>n< / com:Sub>NHC(O)CF<com:Sub>3< / com:Sub> wherein n=3-6; phenyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkylenephenyl, benzhydryl, independently of each other optionally substituted with cyano, nitro, chlorine, fluorine, bromine, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>alkoxy, -<com:Math><semantics>CF3<annotation encoding="application / x-tex">CF_3< / annotation>< / semantics>< / com:Math>. In another very preferred embodiment, said phosphorus moiety R<com:Sub>2< / com:Sub> is represented by formula (X), wherein said R<com:Sub>5< / com:Sub> is methyl, ethyl, 2-cyanoethyl, again preferably 2-cyanoethyl <com:Math><semantics>(CH2)2CN<annotation encoding="application / x-tex">(CH_2)_2CN< / annotation>< / semantics>< / com:Math>). In another very preferred embodiment, said phosphorus moiety R<com:Sub>2< / com:Sub> is represented by formula (X), wherein said R<com:Sub>6< / com:Sub> and R<com:Sub>7< / com:Sub> are independently of each other C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein said heterocyclic ring is selected from pyrollidine, piperidine, morpholine, wherein said heterocyclic ring is optionally substituted with C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub> alkyl, and wherein again further preferably said heterocyclic ring is optionally substituted with methyl. In another very preferred embodiment, said phosphorus moiety R<com:Sub>2< / com:Sub> is represented by formula (X), wherein <com:Math><semantics>R6<annotation encoding="application / x-tex">R_6< / annotation>< / semantics>< / com:Math> is equal to <com:Math><semantics>R7<annotation encoding="application / x-tex">R_7< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R6<annotation encoding="application / x-tex">R_6< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R7<annotation encoding="application / x-tex">R_7< / annotation>< / semantics>< / com:Math> are iso-propyl or methyl. In another very preferred embodiment, said phosphorus moiety R<com:Sub>2< / com:Sub> is represented by formula (X), wherein said R<com:Sub>5< / com:Sub> is methyl, ethyl, 2-cyanoethyl, preferably 2-cyanoethyl, and wherein <com:Math><semantics>R6<annotation encoding="application / x-tex">R_6< / annotation>< / semantics>< / com:Math> is equal to <com:Math><semantics>R7<annotation encoding="application / x-tex">R_7< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R6<annotation encoding="application / x-tex">R_6< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R7<annotation encoding="application / x-tex">R_7< / annotation>< / semantics>< / com:Math> are iso-propyl or methyl. Each alkyl moiety either alone or as part of a larger group such as alkoxy or alkylene is a straight or branched chain and is preferably <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkyl, more preferably <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>alkyl. Examples include methyl, ethyl, n-propyl, prop-2-yl (iso-propyl; interchangeably abbreviated herein as iPr or Pri, in particular in the drawn chemical formula), n-butyl, but-2-yl, 2-methyl- prop-1-yl or 2-methyl-prop-2-yl. Examples of an alkoxy include methoxy, ethoxy, propoxy, iso-propoxy, n-butoxy, sec-butoxy, tert-butoxy, n-pentoxy, neo-pentoxy, n-hexoxy. As described herein, alkoxy may include further substitutents such as halogen atoms leading to haloalkoxy moieties. Each alkylene moiety is a straight or branched chain and is, for example, -CH<com:Sub>2< / com:Sub>-, -CH<com:Sub>2< / com:Sub>- <com:Math><semantics>CH2<annotation encoding="application / x-tex">CH_2< / annotation>< / semantics>< / com:Math>-, <com:Math><semantics>−CH(CH3)<annotation encoding="application / x-tex">-CH(CH_3)< / annotation>< / semantics>< / com:Math>-, <com:Math><semantics>−CH2<annotation encoding="application / x-tex">-CH_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>CH2<annotation encoding="application / x-tex">CH_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>CH2<annotation encoding="application / x-tex">CH_2< / annotation>< / semantics>< / com:Math>-, <com:Math><semantics>−CH(CH3)<annotation encoding="application / x-tex">-CH(CH_3)< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>CH2<annotation encoding="application / x-tex">CH_2< / annotation>< / semantics>< / com:Math>-, or <com:Math><semantics>−CH(CH2CH3)<annotation encoding="application / x-tex">-CH(CH_2CH_3)< / annotation>< / semantics>< / com:Math>-. Each alkenyl moiety either alone or as part of a larger group such as alkenyloxy or alkenylene is a straight or branched chain and is preferably C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, more preferably C<com:Sub>2< / com:Sub>- <com:Math><semantics>C4<annotation encoding="application / x-tex">C_4< / annotation>< / semantics>< / com:Math>alkenyl. Each moiety can be of either the <com:Math><semantics>(E)<annotation encoding="application / x-tex">(E)< / annotation>< / semantics>< / com:Math>- or <com:Math><semantics>(Z)<annotation encoding="application / x-tex">(Z)< / annotation>< / semantics>< / com:Math>-configuration. Examples include vinyl and allyl. A compound of the present invention comprising an alkenyl moiety thus may include, if applicable, either said compound with said alkenyl moiety in its (E)-configuration, said compound with said alkenyl moiety in its <com:Math><semantics>(Z)<annotation encoding="application / x-tex">(Z)< / annotation>< / semantics>< / com:Math>-configuration and mixtures thereof in any ratio. Each alkynyl moiety either alone or as part of a larger group such as alkynyloxy is a straight or branched chain and is preferably C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkynyl, more preferably C<com:Sub>2< / com:Sub>-C<com:Sub>4< / com:Sub>alkynyl. Examples are ethynyl and propargyl. Halogen is fluorine, chlorine, bromine, or iodine, preferably chlorine. In a preferred embodiment, the halogen substituent is chlorine. Each haloalkyl moiety either alone or as part of a larger group such as haloalkoxy is an alkyl group substituted by one or more of the same or different halogen atoms. Examples include difluoromethyl, trifluoromethyl, chlorodifluoromethyl and 2,2,2-trifluoro-ethyl. The term "aryl", as used herein, refers to a monovalent aromatic hydrocarbon radical of 6-14 carbon atoms (<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C14<annotation encoding="application / x-tex">C_{14}< / annotation>< / semantics>< / com:Math>) derived by the removal of one hydrogen atom from a single carbon atom of a parent aromatic ring system as well as said aryl optionally substituted independently with one or more substituents, typically and preferably with one or two substituents as described below. Aryl includes bicyclic radicals comprising an aromatic ring fused to a saturated, partially unsaturated ring, or aromatic carbocyclic or heterocyclic ring. Aryl groups are optionally substituted independently with one or more substituents, typically and preferably with one or two substituents, wherein said substituents are independently at each occurrence selected from C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkyl, halogen, CF<com:Sub>3< / com:Sub>, OH, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkoxy, NR<com:Sub>20< / com:Sub>R<com:Sub>21< / com:Sub>, C<com:Sub>6< / com:Sub>H<com:Sub>5< / com:Sub>, C<com:Sub>6< / com:Sub>H<com:Sub>5< / com:Sub> substituted with halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkoxy, NR<com:Sub>20< / com:Sub>R<com:Sub>21< / com:Sub>, wherein R<com:Sub>20< / com:Sub>, R<com:Sub>21< / com:Sub> are independently at each occurrence H, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl. Typical aryl groups include, but are not limited to, radicals derived from benzene (phenyl), substituted phenyls, naphthalene, anthracene, biphenyl, indenyl, indanyl, 1,2-dihydronapthalene, 1,2,3,4-tetrahydronaphthyl and the like. The term "aryl", as used herein, preferably refers to phenyl optionally substituted with 1 to 3 R<com:Sub>22< / com:Sub>, wherein R<com:Sub>22< / com:Sub> is independently at each occurrence halogen, -OH, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl optionally substituted with one or two OH, C<com:Sub>1< / com:Sub>-C<com:Sub>2< / com:Sub>fluoroalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>2< / com:Sub>alkoxy, C<com:Sub>1< / com:Sub>-C<com:Sub>2< / com:Sub>alkoxyC<com:Sub>1< / com:Sub>- C<com:Sub>3< / com:Sub>alkyl, C<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl, -NH<com:Sub>2< / com:Sub>, NHCH<com:Sub>3< / com:Sub> or N(CH<com:Sub>3< / com:Sub>)<com:Sub>2< / com:Sub>. Where a group is said to be optionally substituted, preferably there are optionally 1-5 substituents, more preferably optionally 1-3 substituents, again more preferably optionally 1 or 2 substituents. Where a group is said to be optionally substituted, and where there are more than one substituents for said optional substitution of said group, said more than one substituents can either be the same or different. The term "nucleobase", as used herein, and abbreviated as B<com:Sub>x< / com:Sub>, refers to unmodified or naturally occurring nucleobases as well as modified or non-naturally occurring nucleobases and synthetic mimetics thereof. A nucleobase is any heterocyclic base that contains one or more atoms or groups of atoms capable of hydrogen bonding to a heterocyclic base of a nucleic acid. In one embodiment, the nucleobase is a purine base or a pyrimidine base, wherein preferably said purine base is purine or substituted purine, and said pyrimidine base is pyrimidine or substituted pyrimidine. More preferably, the nucleobase is (i) adenine (A), (ii) cytosine (C), (iii) 5-methylcytosine (MeC), (iv) guanine (G), (v) uracil (U), or (vi) 5- methyluracil (MeU), or to a derivative of (i), (ii), (iii), (iv), (v) or (vi). The terms "derivative of (i), (ii), (iii), (iv), (v) or (vi), and "nucleobase derivative" are used herein interchangeably. Derivatives of (i), (ii), (iii), (iv), (v) or (vi), and nucleobase derivatives, respectively, are known to the skilled person in the art and are described, for example, in Sharma V. K. et al., Med. Chem. Commun., 2014, 5, 1454-1471, and include without limitation 5-hydroxymethyl cytosine, xanthine, hypoxanthine, 2-aminoadenine, alkyl adenine, such as 6-methyl adenine, 2-propyl adenine, alkyl guanine, such as 6-methyl guanine, 2-propyl guanine, 2-thiouracil, 2- thiothymine and 2-thiocytosine, 5-halo uracil, 5-halo cytosine, alkynyl pyrimidine bases, such as 5-propynyl (-C=C-CH<com:Sub>3< / com:Sub>) uracil, 5-propynyl (-C=C-CH<com:Sub>3< / com:Sub>) cytosine, 6-azo uracil, 6-azo cytosine, 6-azo thymine, pseudo-uracil, 4-thiouracil; 8-substituted purine bases, such as 8- halo-, 8-amino-, 8-thiol-, 8-thioalkyl-, 8-hydroxyl-adenine or guanine, 5-substituted pyrimidine bases, such as 5-halo-, particularly 5-bromo-, 5-trifluoromethyl-uracil or - cytosine; 7-methylguanine, 7-methyladenine, 2-F-adenine, 2-amino-adenine, 8-azaguanine and 8-azaadenine, 7-deazaguanine, 7-deazaadenine, 3-deazaguanine, 3-deazaadenine, hydrophobic bases, promiscuous bases, size-expanded bases, or fluorinated bases. In certain embodiments, the nucleobase includes without limitation tricyclic pyrimidines, such as 1,3- diazaphenoxazine-2-one, 1,3-diazaphenothiazine-2-one or 9-(2-aminoethoxy)-1,3- diazaphenoxazine-2-one (G-clamp). The term "nucleobase derivative" also includes those in which the purine or pyrimidine base is replaced by other heterocycles, for example 7-deaza- adenine, 7-deazaguanosine, 2-aminopyridine or 2-pyridone. Further nucleobases of the invention include without limitation those known to skilled artisan (e.g. US patent 3,687,808; Swayze et al., The Medicinal Chemistry of Oligonucleotides, in Antisense a Drug Technology, Chapter 6, pp. 143-182 (Crooke, S.T., ed., 2008); The Concise Encyclopedia Of Polymer Science And Engineering, Kroschwitz, J.I., Ed., John Wiley & Sons, 1990, pp. 858- 859; Englisch et al., Angewandte Chemie, International Edition, 1991, Vol. 30 (6), pp. 613- 623; Sanghvi, Y.S., Antisense Research and Applications, Crooke, S.T. and Lebleu, B., Eds., CRC Press, 1993, pp. 273-302). Preferred nucleobase derivatives include methylated adenine, guanine, uracil and cytosine and nucleobase derivatives, preferably of (i), (ii), (iii) or (iv), wherein the respective amino groups, preferably the exocyclic amino groups, are protected by acyl protecting groups or dialkylformamidino, preferably dimethylformamidino (DMF), and further include nucleobase derivatives such as 2-fluorouracil, 2-fluorocytosine, 5-bromouracil, 5-iodouracil, 2,6-diaminopurine, azacytosine and pyrimidine analogs such as pseudoisocytosine and pseudouracil. In a further preferred embodiment, said nucleobase derivative is selected from methylated adenine, methylated guanine, methylated uracil and methylated cytosine, and from a nucleobase derivative of (i), (ii), (iii) or (iv), wherein the respective amino groups, preferably the exocyclic amino groups, are protected by a protecting group. In a further preferred embodiment, said nucleobase derivative is selected from methylated adenine, methylated guanine, methylated uracil and methylated cytosine, and from a nucleobase derivative of (i), (ii), (iii) or (iv), wherein the respective amino groups, preferably the exocyclic amino groups, are protected by acyl protecting groups or dialkylformamidino, preferably dimethylformamidino (DMF). In a further preferred embodiment, said nucleobase derivative is selected from a nucleobase derivative of (i), (ii), (iii) or (iv), wherein the respective amino groups, preferably the exocyclic amino groups, are protected by a protecting group. In a further preferred embodiment, said nucleobase derivative is a nucleobase derivative of (i), (ii), (iii) or (iv), wherein the exocyclic amino groups, are protected by acyl protecting groups or dialkylformamidino, preferably dimethylformamidino (DMF). In a further very preferred embodiment, said acyl protecting group of said exocyclic amino group of said nucleobase derivative of (i), (ii), (iii) or (iv) is -C(O)-R<com:Sub>11< / com:Sub>, wherein independently of each other R<com:Sub>11< / com:Sub> is selected from C<com:Sub>1< / com:Sub>-C<com:Sub>10< / com:Sub>alkyl, C<com:Sub>6< / com:Sub>-C<com:Sub>10< / com:Sub>aryl, C<com:Sub>6< / com:Sub>-C<com:Sub>10< / com:Sub>arylC<com:Sub>1< / com:Sub>- <com:Math><semantics>C10<annotation encoding="application / x-tex">C_{10}< / annotation>< / semantics>< / com:Math>alkylene, or <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C10<annotation encoding="application / x-tex">C_{10}< / annotation>< / semantics>< / com:Math>aryloxy<com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C10<annotation encoding="application / x-tex">C_{10}< / annotation>< / semantics>< / com:Math>alkylene and wherein said dialkylformamidino protecting group is <com:Math><semantics>=C(H)−NR12R13<annotation encoding="application / x-tex">=C(H)-NR_{12}R_{13}< / annotation>< / semantics>< / com:Math>, wherein <com:Math><semantics>R12<annotation encoding="application / x-tex">R_{12}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R13<annotation encoding="application / x-tex">R_{13}< / annotation>< / semantics>< / com:Math> are independently of each other selected from <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C4<annotation encoding="application / x-tex">C_4< / annotation>< / semantics>< / com:Math>alkyl. In a further very preferred embodiment, said acyl protecting group of said exocyclic amino group of said nucleobase derivative of (i), (ii), (iii) or (iv) is -C(O)-R<com:Sub>14< / com:Sub>, wherein independently of each other R<com:Sub>14< / com:Sub> is selected from C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkyl; phenyl; phenyl substituted with halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, C<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkoxy; benzyl; benzyl substituted with halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, C<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkoxy; or phenyloxyC<com:Sub>1< / com:Sub>-C<com:Sub>2< / com:Sub>alkylene optionally substituted with halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkoxy; and wherein said dialkylformamidino protecting group is <com:Math><semantics>=C(H)−NR12R13<annotation encoding="application / x-tex">=C(H)-NR_{12}R_{13}< / annotation>< / semantics>< / com:Math>, wherein <com:Math><semantics>R12<annotation encoding="application / x-tex">R_{12}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R13<annotation encoding="application / x-tex">R_{13}< / annotation>< / semantics>< / com:Math> are independently of each other selected from <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C4<annotation encoding="application / x-tex">C_4< / annotation>< / semantics>< / com:Math>alkyl. In a further very preferred embodiment, said acyl protecting group of said exocyclic amino group of said nucleobase derivative of (i), (ii), (iii) or (iv) is -C(O)-R<com:Sub>15< / com:Sub>, wherein independently of each other R<com:Sub>15< / com:Sub> is selected from C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkyl; phenyl; phenyl substituted with halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkyl, C<com:Sub>5< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkoxy; benzyl; benzyl substituted with halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkoxy; or phenyloxymethylene (CH<com:Sub>2< / com:Sub>-OC<com:Sub>6< / com:Sub>H<com:Sub>5< / com:Sub>) wherein the phenyl is optionally substituted with halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkyl, C<com:Sub>5< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkoxy; and wherein said dialkylformamidino protecting group is <com:Math><semantics>=C(H)−NR12R13<annotation encoding="application / x-tex">=C(H)-NR_{12}R_{13}< / annotation>< / semantics>< / com:Math>, wherein <com:Math><semantics>R12<annotation encoding="application / x-tex">R_{12}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R13<annotation encoding="application / x-tex">R_{13}< / annotation>< / semantics>< / com:Math> are independently of each other selected from <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C4<annotation encoding="application / x-tex">C_4< / annotation>< / semantics>< / com:Math>alkyl. In a further very preferred embodiment, said acyl protecting group of said exocyclic amino group of said nucleobase derivative of (i), (ii), (iii) or (iv) is -C(O)-R<com:Sub>16< / com:Sub>, wherein independently of each other R<com:Sub>16< / com:Sub> is selected from C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl; phenyl; phenyl substituted with <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>alkyl, methoxy; benzyl; benzyl substituted with <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>alkyl, methoxy; or phenyloxymethylene (<com:Math><semantics>CH2<annotation encoding="application / x-tex">CH_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>OC6H5<annotation encoding="application / x-tex">OC_6H_5< / annotation>< / semantics>< / com:Math>) wherein the <com:Math><semantics>C6H5<annotation encoding="application / x-tex">C_6H_5< / annotation>< / semantics>< / com:Math> is optionally substituted with <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>- <com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>alkyl, methoxy; and wherein said dialkylformamidino protecting group is <com:Math><semantics>=C(H)−NR12R13<annotation encoding="application / x-tex">=C(H)-NR_{12}R_{13}< / annotation>< / semantics>< / com:Math>, wherein <com:Math><semantics>R12<annotation encoding="application / x-tex">R_{12}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R13<annotation encoding="application / x-tex">R_{13}< / annotation>< / semantics>< / com:Math> are independently of each other selected from <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C4<annotation encoding="application / x-tex">C_4< / annotation>< / semantics>< / com:Math>alkyl. In a further very preferred embodiment, said acyl protecting group of said exocyclic amino group of said nucleobase derivative of (i), (ii), (iii) or (iv) is -C(O)-R<com:Sub>17< / com:Sub>, wherein independently of each other R<com:Sub>17< / com:Sub> is selected from C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl; phenyl; phenyl substituted with C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl, methoxy; benzyl; benzyl substituted with C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl, methoxy; or phenyloxymethylene (<com:Math><semantics>CH2<annotation encoding="application / x-tex">CH_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>OC6H5<annotation encoding="application / x-tex">OC_6H_5< / annotation>< / semantics>< / com:Math>) wherein the <com:Math><semantics>C6H5<annotation encoding="application / x-tex">C_6H_5< / annotation>< / semantics>< / com:Math> is optionally substituted with <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>- C<com:Sub>3< / com:Sub>alkyl, methoxy; and wherein said dialkylformamidino protecting group is dimethylformamidino (DMF). In a further very preferred embodiment, said acyl protecting group of said exocyclic amino group of said nucleobase derivative of (i), (ii), (iii) or (iv) is -C(O)-R<com:Sub>18< / com:Sub>, wherein independently of each other R<com:Sub>18< / com:Sub> is selected from methyl, iso-propyl, phenyl, benzyl, or phenyloxymethylene (<com:Math><semantics>CH2<annotation encoding="application / x-tex">CH_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>OC6H5<annotation encoding="application / x-tex">OC_6H_5< / annotation>< / semantics>< / com:Math>) wherein the <com:Math><semantics>C6H5<annotation encoding="application / x-tex">C_6H_5< / annotation>< / semantics>< / com:Math> is optionally substituted with <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>- C<com:Sub>3< / com:Sub>alkyl, methoxy; and wherein said dialkylformamidino protecting group is dimethylformamidino (DMF). In a further very preferred embodiment, said acyl protecting group of said exocyclic amino group of said nucleobase derivative of (i), (ii), (iii) or (iv) is -C(O)-R<com:Sub>19< / com:Sub>, wherein independently of each other R<com:Sub>19< / com:Sub> is selected from methyl, iso-propyl, phenyl, benzyl, or phenyloxymethylene (<com:Math><semantics>CH2<annotation encoding="application / x-tex">CH_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>OC6H5<annotation encoding="application / x-tex">OC_6H_5< / annotation>< / semantics>< / com:Math>) wherein the <com:Math><semantics>C6H5<annotation encoding="application / x-tex">C_6H_5< / annotation>< / semantics>< / com:Math> is optionally substituted with methyl, iso-propyl; and wherein said dialkylformamidino protecting group is dimethylformamidino (DMF). The term "dialkylformamidino", as used herein refers to <com:Math><semantics>=C(H)−NR12R13<annotation encoding="application / x-tex">=C(H)-NR_{12}R_{13}< / annotation>< / semantics>< / com:Math>, wherein <com:Math><semantics>R12<annotation encoding="application / x-tex">R_{12}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R13<annotation encoding="application / x-tex">R_{13}< / annotation>< / semantics>< / com:Math> are independently of each other selected from <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C4<annotation encoding="application / x-tex">C_4< / annotation>< / semantics>< / com:Math>alkyl. In preferred embodiments, said dialkylformamidino is a protecting group of said exocyclic amino group of said nucleobase derivative of (i), (ii), (iii) or (iv). The resulting compounds may be of either the (E)- or (Z)-configuration and both forms, and mixtures thereof in any ratio, should be included within the scope of the present invention. In a preferred embodiment the inventive compounds comprise the dialkylformamidino, preferably dimethylformamidino (DMF), in the (Z) configuration. According to one embodiment, Bx is selected from uracil, thymine, cytosine, 5- methylcytosine, adenine and guanine. Preferably, Bx is selected from thymine, 5- methylcytosine, adenine and guanine. According to one embodiment, Bx is an aromatic heterocyclic moiety capable of forming base pairs when incorporated into DNA or RNA oligomers in lieu of the bases uracil, thymine, cytosine, 5-methylcytosine, adenine and guanine. The term „nucleosidic linkage group“, as used herein, refers to any linkage group known in the art that is able to link, preferably links, said inventive compound of formula (IV), (V) or (VI) to a further compound, preferably to a nucleosidic compound including a further inventive compound of formula (IV), (V) or (VI), within the oligomers in accordance with the present invention. Representative patents that teach such possible linkage groups are without limitation US patent 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; 5,608,046; 5,610,289; 5,618,704; 5,623,070; 5,663,312; 5,633,360; 5,677,437; 5,677,439; 5,646,269 and 5,792,608. Said further compound is selected from a nucleosidic compound or a non-nucleosidic compound. Said nucleosidic compound includes without limitation, and is typically and preferably selected from, at least one (i) nucleoside, (ii) nucleotide, (iii) oligonucleotide or (iv) modifications of (i), (ii) or (iii). Said non-nucleosidic compound includes, and is typically and preferably selected from, a peptide, protein, silicate compounds or even a solid support. The solid support includes without a limitation surfaces, beads, glass supports, polymers or resins. In a preferred embodiment, the glass is controlled-pore glass, preferably with 500 Å, 1000 Å or 2000 Å pores. The beads include without limitation glass beads, preferably controlled-pore glass, or magnetic beads. The polymer includes without limitation polystyrenes including for example divinylbenzene, styrene, and chloromethylstyrene. In a preferred embodiment, the solid support are highly cross-linked polystyrene beads. The term "nucleosidic linkage group" includes phosphorus linkage groups and non- phosphorus linkage groups. Non-phosphorus linkage groups do not contain a phosphorus atom and examples of non-phosphorus linkage groups include, and is typically and preferably selected from, alkyl, aryl, preferably, phenyl, benzyl, or benzoyl, cycloalkyl, alkylenearyl, alkylenediaryl, alkoxy, alkoxyalkylene, alkylsulfonyl, alkyne, ether, each independently of each other optionally substituted with cyano, nitro, halogen; carboxyl, amide, amine, amino, imine, thiol, sulfide, sulfoxide, sulfone, sulfamate, sulfonate, sulfonamide, siloxane or mixtures thereof. In a preferred embodiment, the non-phosphorus linkage group is amino propyl, long chain alkyl amine group, inyl, acetylamide, aminomethyl, formacetal, thioformacetal, thioformacetyl, riboacetyl, methyleneimino, methylenehydrazino or a neutral non-ionic nucleoside linkage group, such as amide-3 (3'-CH<com:Sub>2< / com:Sub>-C(=O)-N(H)-5') or amide-4 (3'- CH<com:Sub>2< / com:Sub>-N(H)-C(=O)-5'). In a preferred embodiment, the non-phosphorus linkage group includes a compound selected from alkyl, aryl, preferably phenyl, benzyl, or benzoyl, cycloalkyl, alkylenearyl, alkylenediaryl, alkoxy, alkoxyalkylene, alkylsulfonyl, alkyne, or ether, wherein the compound includes C<com:Sub>1< / com:Sub>-C<com:Sub>9< / com:Sub>, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>, or C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>. In a preferred embodiment, said nucleosidic linkage group is a phosphorus linkage group, and said phosphorus linkage group refers to a moiety comprising a phosphorus atom in the <com:Math><semantics>PIII<annotation encoding="application / x-tex">P^{III}< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>PV<annotation encoding="application / x-tex">P^{V}< / annotation>< / semantics>< / com:Math> valence state represented by formula (XI): [Image disponible dans le document PDF, Image available in the PDF document] (XI), wherein W represents O, S, Se or an electron pair; preferably W represents O or S; R<com:Sub>10< / com:Sub> is H, halogen, OH, OR<com:Sub>5< / com:Sub>, NR<com:Sub>6< / com:Sub>R<com:Sub>7< / com:Sub>, SH, SR<com:Sub>8< / com:Sub>, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>- C<com:Sub>6< / com:Sub>alkoxy, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>haloalkoxy, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>aminoalkyl; wherein R<com:Sub>5< / com:Sub> is C<com:Sub>1< / com:Sub>-C<com:Sub>9< / com:Sub>alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkoxy, each independently of each other optionally substituted with cyano, nitro, halogen, -NHC(O)C<com:Sub>1< / com:Sub>- C<com:Sub>3< / com:Sub>alkyl, -NHC(O)<com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>haloalkyl, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>alkylsulfonyl; aryl, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkylenearyl, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>- C<com:Sub>6< / com:Sub>alkylenediaryl, each independently of each other optionally substituted with cyano, nitro, halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkoxy, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>haloalkoxy, NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl, NHC(O)C<com:Sub>1< / com:Sub>- C<com:Sub>3< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkylsulfonyl; acetyl; a hydroxyl protecting group; wherein R<com:Sub>6< / com:Sub> and R<com:Sub>7< / com:Sub> are independently of each other hydrogen, C<com:Sub>1< / com:Sub>-C<com:Sub>9< / com:Sub>alkyl optionally substituted with cyano, nitro, halogen, C2-C6alkenyl, C3-C6cycloalkyl, C1-C3alkoxy; aryl optionally substituted with cyano, nitro, halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkoxy; an amino protecting group; or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein preferably said heterocyclic ring is selected from pyrollidinyl, piperidinyl, morpholinyl, piperazinyl and homopiperazine, wherein said heterocyclic ring is optionally substituted with C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub> alkyl; and wherein R<com:Sub>8< / com:Sub> is a thiol protecting group; and wherein each of the wavy lines indicates the attachment of said phosphorus linkage group of formula (XI) to a further compound, preferably to a nucleosidic compound including a further inventive compound of formula (IV), (V) or (VI), within the oligomers in accordance with the present invention. When W represents O, S or Se then said P atom within said phosphorus moiety is in its P<com:Sup>V< / com:Sup> valence state. When W represents an electron pair then said P atom within said phosphorus moiety is in its P<com:Sup>III< / com:Sup> valence. The moiety of formula (XI) includes any possible stereoisomer. Further included in said moieties represented by formula (XI) are salts thereof, wherein typically and preferably said salts are formed upon treatment with inorganic bases or amines, and are typically and preferably salts derived from reaction with the OH or SH groups being (independently of each other) said R<com:Sub>10< / com:Sub>. Preferred inorganic bases or amines leading to said salt formation with the OH or SH groups are well known in the art and are typically and preferably trimethylamine, diethylamine, methylamine or ammonium hydroxide. These phosphorus moieties included in the present invention are, if appropriate, also abbreviated as "O'HB", wherein said HB refers to the counter cation formed. In a preferred embodiment, in the phosphorus linkage group of formula (XI), R<com:Sub>6< / com:Sub> and R<com:Sub>7< / com:Sub> are independently of each other hydrogen, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl optionally substituted with cyano, nitro, halogen, C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl; aryl optionally substituted with cyano, nitro, halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub> alkyl; or an amino protecting group. In a preferred embodiment, in the phosphorus linkage group of formula (XI), W represents O or S; R<com:Sub>10< / com:Sub> is H, OH, OR<com:Sub>5< / com:Sub>, NR<com:Sub>6< / com:Sub>R<com:Sub>7< / com:Sub>, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>- C<com:Sub>6< / com:Sub>alkoxy, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>haloalkoxy, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>aminoalkyl; wherein R<com:Sub>5< / com:Sub> is C<com:Sub>1< / com:Sub>-C<com:Sub>9< / com:Sub>alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkoxy, each independently of each other optionally substituted with cyano, nitro, halogen, -NHC(O)C<com:Sub>1< / com:Sub>- <com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>alkyl, -NHC(O)<com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>haloalkyl, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>alkylsulfonyl; aryl, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>alkylenearyl, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>- C<com:Sub>6< / com:Sub>alkylenediaryl each independently of each other optionally substituted with cyano, nitro, halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>alkoxy, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>4< / com:Sub>haloalkoxy, -NHC(O)C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkyl, NHC(O)C<com:Sub>1< / com:Sub>- C<com:Sub>3< / com:Sub>haloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkylsulfonyl; acetyl; or a hydroxyl protecting group; wherein R<com:Sub>6< / com:Sub> and R<com:Sub>7< / com:Sub> are independently of each other hydrogen, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub>alkyl optionally substituted with cyano, nitro, halogen, C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>alkenyl, C<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub>cycloalkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkoxy; aryl optionally substituted with cyano, nitro, halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub> alkyl, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub>alkoxy; an amino protecting group; and wherein R<com:Sub>8< / com:Sub> is a thiol protecting group. In further preferred embodiment, said nucleosidic linkage group is a phosphorus linkage group, and said phosphorus linkage group is selected from a phosphodiester linkage group, a phosphotriester linkage group, a phosphorothioate linkage group, a phosphorodithioate linkage group, a phosphonate linkage group, preferably a H-phosphonate linkage group or a methylphosphonate linkage group; a phosphonothioate linkage group, preferably a H-phosphonothioate linkage group, a methyl phosphonothioate linkage group; a phosphinate linkage group, a phosphorthioamidate linkage, a phosphoramidate linkage group, or a phosphite linkage group. In another very preferred embodiment, said nucleosidic linkage group is a phosphorus linkage group, and wherein said phosphorus linkage group is selected from a phosphodiester linkage group, a phosphotriester linkage group, a phosphorothioate linkage group, or a phosphonate linkage group, wherein the phosphonate is preferably a H- phosphonate linkage group or methylphosphonate linkage group. In another very preferred embodiment, said nucleosidic linkage group is a phosphorus linkage group, and wherein said phosphorus linkage group is a phosphodiester linkage group. In another very preferred embodiment, said nucleosidic linkage group is a phosphorus linkage group, and wherein said phosphorus linkage group is a phosphorothioate linkage group. In a preferred embodiment, the phosphorus linkage group is selected from an alkyl phosphodiester linkage group, an alkylene phosphodiester linkage group, a thionoalkyl phosphodiester linkage group or an aminoalkyl phosphodiester linkage group, an alkyl phosphotriester linkage group, an alkylene phosphotriester linkage group, a thionoalkyl phosphotriester linkage group or an aminoalkyl phosphotriester linkage group, an alkyl phosphonate linkage group, an alkylene phosphonate linkage group, an aminoalkyl phosphonate linkage group, a thionoalkyl phosphonate linkage group or a chiral phosphonate linkage group. More preferably, said nucleosidic linkage group is a phosphorus linkage group, and wherein said phosphorus linkage group is a is a phosphodiester linkage group -O- <com:Math><semantics>P(=O)(OH)O<annotation encoding="application / x-tex">P(=O)(OH)O< / annotation>< / semantics>< / com:Math>- or <com:Math><semantics>−O−P(=O)(O−)O<annotation encoding="application / x-tex">-O-P(=O)(O^{-})O< / annotation>< / semantics>< / com:Math>- with <com:Math><semantics>[HB+]<annotation encoding="application / x-tex">[HB^{+}]< / annotation>< / semantics>< / com:Math> as counterion, a phosphorothicate <com:Math><semantics>−O<annotation encoding="application / x-tex">-O< / annotation>< / semantics>< / com:Math>- P(=S)(OH)O- or -O-P(=S)(O-)O- with [HB+] as counterion, a methylphosphonate -O- P(=O)(CH<com:Sub>3< / com:Sub>)O-. Various salts, mixed salts and free acid forms of the phosphorus linkage group are included. In a further embodiment, said nucleosidic linkage group links a nucleoside, nucleotide or oligonucleotide with a further nucleoside, nucleotide or oligonucleotide. The wavy line within formulas (I) and (IV) symbolizing the bond between the Bx and and the bicyclic core of the inventive compounds indicates that any spatial orientation of the nucleobase Bx are covered by formula (I) or (IV). That means that formulas (I) and (IV) cover either the alpha or the beta conformation or any mixture of alpha and beta anomers of the inventive compounds. As used herein, the term "nucleoside" refers to a compound comprising a nucleobase and a sugar covalently linked to said nucleobase. The term "nucleotide", as used herein, refers to a nucleoside further comprising a nucleosidic linkage group or phosphorus moiety, wherein said nucleosidic linkage group or said phosphorus moiety is covalently linked to the sugar of said nucleoside. As used herein the term "nucleoside" or "nucleotide" is meant to include all manner of naturally occurring or modified nucleosides or nucleoside mimetics, or naturally occurring or modified nucleotides or nucleotide mimetics, respectively, that can be incorporated into an oligomer using natural or chemical oligomer synthesis. Typically and preferably, the term "nucleoside", as used herein, refers to a naturally occurring nucleoside, a modified nucleoside or nucleoside mimetic. Typically and preferably, the term "nucleotide", as used herein, refers to a naturally occurring nucleotide, a modified nucleotide or nucleotide mimetic. The term "modified nucleosides" is intended to include modifications made to the sugar and / or nucleobase of a nucleoside as known to the skilled person in the art and described herein. The term "modified nucleotides" is intended to include modifications made to the sugar and / or nucleobase and / or nucleosidic linkage group or phosphorus moiety of a nucleotide as known to the skilled person in the art and described herein. The term "nucleoside mimetic" is intended to include those structures used to replace the sugar and the nucleobase. Examples of nucleoside mimetics include nucleosides wherein the nucleobase is replaced with a phenoxazine moiety (for example the 9-(2-aminoethoxy)- 1,3-diazaphenoxazine-2-one group) and the sugar moiety is replaced a cyclohexenyl or a bicyclo[3.1.0]hexyl moiety. The term "nucleotide mimetic" as used herein is meant to include nucleotides used to replace the sugar and the nucleosidic linkage group. Examples of nucleotide mimetics include peptide nucleic acids (PNA) or morpholinos. The term "nucleoside" or "nucleotide" also includes combinations of modifications, such as more than one nucleobase modification, more than one sugar modification or at least one nucleobase and at least one sugar modification. The sugar of the nucleoside or nucleotide includes without limitation a monocyclic, bicyclic or tricyclic ring system, preferably a tricyclic or bicyclic system or a monocyclic ribose or de(s)oxyribose. Modifications of the sugar further include but are not limited to modified stereochemical configurations, at least one substitution of a group or at least one deletion of a group. A modified sugar is typically and preferably a modified version of the ribosyl moiety as naturally occurring in RNA and DNA (i.e. the furanosyl moiety), such as bicyclic sugars, tetrahydropyrans, 2'-modified sugars, 3'-modified sugars, 4'-modified sugars, 5'-modified sugars, or 4'-substituted sugars. Examples of suitable sugar modifications are known to the skilled person and include, but are not limited to 2', 3' and / or 4' substituted nucleosides (e.g. 4'-S-modified nucleosides); 2'-O-modified RNA nucleotide residues, such as 2'-O-alkyl or 2'-O-(substituted)alkyl e.g. 2'-O-methyl, 2'-O-(2-cyanoethyl), 2'-O-(2- methoxy)ethyl (2'-MOE), 2'-O-(2-thiomethyl)ethyl; 2'-O-(haloalkoxy)methyl e.g. 2'-O-(2- chloroethoxy)methyl (MCEM), 2'-O-(2,2-dichloroethoxy)methyl (DCEM); 2'-O- alkoxycarbonyl e.g. 2'-O-[2-(methoxycarbonyl)ethyl] (MOCE), 2'-O-[2-(N- methylcarbamoyl)ethyl] (MCE), 2'-O-[2-(N,N-dimethylcarbamoyl)ethyl] (DMCE), in particular a 2'-O-methyl modification or a 2'-O-methoxyethyl (2'-O-MOE); or other modified sugar moieties, such as morpholino (PMO), cationic morpholino (PMOPlus) or a modified morpholino group, such as PMO-X. The term "PMO-X" refers to a modified morpholino group comprising at least one 3' or 5' terminal modification, such 3'-fluorescent tag, 3' quencher (e.g. 3'-carboxyfluorescein, 3'-Gene Tools Blue, 3'-lissamine, 3'-dabcyl), 3'-affinity tag and functional groups for chemical linkage (e.g. 3'-biotin, 3'-primary amine, 3'-disulfide amide, 3'-pyridyl dithio), 5'-end modifications (5'-primary amine, 5'-dabcyl), 3'-azide, 3'- alkyne, 5'-azide, 5'-alkyne, or as disclosed in WO2011 / 150408 and US2012 / 0065169. "Bicylic sugar moieties" comprise two interconnected ring systems, e.g. bicyclic nucleosides wherein the sugar moiety has a 2'-O-CH(alkyl)-4' or 2'-O-CH2-4' group, locked nucleic acid (LNA), xylo-LNA, alpha-L-LNA, beta-D-LNA, cEt (2'-O,4'-C constrained ethyl) LNA, cMOEt (2'-O,4'-C constrained methoxyethyl) LNA, ethylene-bridged nucleic acid (ENA), hexitol nucleic acid (HNA), fluorinated HNA (F-HNA), pyranosyl-RNA (p-RNA), or 3'-deoxypyranosyl-DNA (p-DNA). Alternatively, the sugar of the nucleoside or nucleotide includes a tricyclic sugar moiety as, for example, described in WO 2013 / 135900 and WO 2014 / 140348. The term "oligomer", as used herein, refers to a compound comprising two or more monomer subunits linked by nucleosidic linkage groups, wherein at least one of said two or more monomer subunits is a compound of the formula (IV), preferably a compound of the formula (V) or a compound of the formula (VI). In a preferred embodiment, the oligomer comprises at least one compound of formula (IV), (V) or (VI) and at least one ribonucleotide or deoxyribonucleotide. More preferably, the oligomer comprises at least one compound of formula (IV), (V) or (VI) and at least one deoxyribonucleotide. The term "monomer subunit", as used herein, is meant to include all manner of monomer units that are amenable to oligomer synthesis including, and typically and preferably referring to, monomer subunits such as <com:Math><semantics>α<annotation encoding="application / x-tex">\alpha< / annotation>< / semantics>< / com:Math>-D-ribonucleosides, <com:Math><semantics>β<annotation encoding="application / x-tex">\beta< / annotation>< / semantics>< / com:Math>-D-ribonucleosides, <com:Math><semantics>α<annotation encoding="application / x-tex">\alpha< / annotation>< / semantics>< / com:Math>-D-2'-deoxyribnucleosides, <com:Math><semantics>β<annotation encoding="application / x-tex">\beta< / annotation>< / semantics>< / com:Math>-D-2'-deoxyribnucleosides, naturally occurring nucleosides, naturally occurring nucleotides, modified nucleosides, modified nucleotides, mimetics of nucleosides, mimetics of nucleotides, and the inventive compounds provided herein including any compounds of any one of the formulas (I) to (VI). In a preferred embodiment, the oligomer is an oligonucleotide. The term "oligonucleotide", as used herein, refers to a compound comprising at least two nucleosides linked to each other each by a nucleosidic linkage group. Thus, the term "oligonucleotide", as used herein, includes, and typically and preferably refer to, compounds comprising at least two nucleosides linked by nucleosidic linkage groups, wherein said at least two nucleosides are independently selected from naturally occurring nucleosides, modified nucleosides or nucleoside mimetics. Thus, the term "oligonucleotide", as used herein, includes compounds comprising naturally occurring nucleotides, modified nucleotides or nucleotide mimetics and, thus, the term "oligonucleotide", as used herein, includes oligonucleotides with modifications made to the sugar and / or nucleobase and / or nucleosidic linkage group as known to the skilled person in the art and described herein. The oligomer can be single stranded or double stranded. In one embodiment, the oligomer is double stranded (i.e. a duplex). In a preferred embodiment, the oligomer is single stranded. In a preferred embodiment the oligomer is coupled to a non-nucleosidic compound, preferably a solid support. The solid support is preferably selected from beads, polymers or resin. In a certain embodiment, the oligomer has a length of up to 40 monomer subunits, preferably up to 30 monomer subunits, more preferably up to 30 monomer subunits, again more preferably up to 20 monomer subunits or up to 15 monomer subunits. In a further embodiment, said oligomer comprises from 5 to 40 monomeric subunits, preferably from 8 to 30 monomer subunits, more preferably from 8 to 25 monomer subunits, again more preferably from 8 to 20 monomer subunits. In certain embodiments, the oligomer as provided herein is modified by covalent attachment of one or more terminal groups to the 5' or 7' terminus of the oligomer. A terminal group can also be attached at any of the termini of the oligomer. The term "' terminus" refers to the end or terminus of the oligomer, nucleic acid sequence or the compound of formula (IV), (V) or (VI), wherein the integer (3', 5' or 7' etc.) indicates to the carbon atom of the sugar included in the nucleoside of the oligomer, nucleic acid sequence or the compound of formula (IV), (V) or (VI). The term ,,5' terminal group" or "7' terminal group", as used herein, refers to a group located at the 5' terminus or 7' terminus, respectively, of the sugar included in the compound of formula (IV), (V) or (VI). Examples of the „5' terminal group“ or “7' terminal group“ include without limitation a capping group, diphosphate, triphosphate, label, such as a fluorescent label (e.g. fluorescein or rhodamine), dye, reporter group suitable for tracking the oligomer, solid support, non-nucleosidic group, antibody or conjugate group. Preferably a „5’ terminal group“ or “7’ terminal group“ is selected from a diphosphate, triphosphate, fluorescent label, dye, reporter group that can track the oligomer, solid support, non-nucleosidic group, antibody or conjugate group. In certain embodiments, the oligomer as provided herein or the compound of formula (IV), (V) or (VI) is modified by covalent attachment of one or more conjugate groups. In general, conjugate groups modify one or more properties of the compound they are attached to. Such properties include without limitation, nuclease stability, binding affinity, pharmacodynamics, pharmacokinetics, binding, absorption, cellular distribution, cellular uptake, delivery, charge and clearance. Conjugate groups are routinely used in the chemical arts and are linked directly or via an optional linkage group to a parent compound such as an oligomer. The term "conjugate group" includes without limitation, and refers preferably to intercalators, polyamines, polyamides, polyethylene glycols, thioethers, polyethers, cholesterols, thiocholesterols, cholic acid moieties, folate, lipids, phospholipids, biotin, phenazine, phenanthridine, anthraquinone, adamantane, acridine, lipophilic moieties, or coumarins. The term "nucleic acid" or "nucleic acid sequence", as interchangeably used herein, is understood as oligomeric or polymeric molecule comprising at least two interlinked nucleotides or at least two nucleosides linked by a nucleosidic linkage group. In the context of the present invention, the nucleic acid includes ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) and is preferably selected from naturally occurring RNA, naturally occurring DNA, modified DNA, modified RNA, mixtures thereof, such as RNA-DNA hybrids. The modification may comprise the backbone such as the nucleosidic linkage group and / or the nucleoside and / or the sugar as further described herein. The nucleic acids can be synthesized chemically or enzymatically by polymerases. The term "natural" or "naturally occurring", as interchangeably used herein, refers to compounds that are of natural origin. The term "stereoisomers" refers to compounds, which have identical chemical constitution, but differ with regard to the arrangement of the atoms or groups in space. "Diastereomer" refers to a stereoisomer with two or more centers of chirality in which the compounds are not mirror images of one another. Diastereomers have different physical properties, e.g. melting points, boiling points, spectral properties, and chemical and biological reactivities. Mixtures of diastereomers may be separated under high resolution analytical procedures such as electrophoresis and chromatography. "Enantiomers" refer to two stereoisomers of a compound which are non-superimposable mirror images of one another. Stereochemical definitions and conventions used herein generally follow S.P. Parker, Ed., McRaw-Hiff Dictionary of Chemical Terms (1984), McGraw-Hill Book Company, New York; and Eliel, E. and Wilen, S., "Stereochemistry of Organic Compounds", John Wiley & Sons, Inc., New York, 1994. As used herein, "T<com:Sub>m< / com:Sub>" (melting temperature) is the temperature at which two strands of a duplex nucleic acid separate. The T<com:Sub>m< / com:Sub> is often used as a measure of duplex stability of an antisense compound toward a complementary nucleic acid. In a first aspect, the present invention provides a compound of formula (I): [Image disponible dans le document PDF, Image available in the PDF document] (I) wherein one of <com:Math><semantics>T1<annotation encoding="application / x-tex">T_1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>T2<annotation encoding="application / x-tex">T_2< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>OR1<annotation encoding="application / x-tex">OR_1< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>OR2<annotation encoding="application / x-tex">OR_2< / annotation>< / semantics>< / com:Math>; and the other of <com:Math><semantics>T1<annotation encoding="application / x-tex">T_1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>T2<annotation encoding="application / x-tex">T_2< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>OR1<annotation encoding="application / x-tex">OR_1< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>OR2<annotation encoding="application / x-tex">OR_2< / annotation>< / semantics>< / com:Math>; wherein R<com:Sub>1< / com:Sub> is H or a hydroxyl protecting group, and R<com:Sub>2< / com:Sub> is a phosphorus moiety; and wherein Bx is a nucleobase. In a preferred embodiment, said compound of formula (I) of the invention is a compound of formula (II) [Image disponible dans le document PDF, Image available in the PDF document] (II) wherein (i) <com:Math><semantics>T1<annotation encoding="application / x-tex">T_1< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>OR1<annotation encoding="application / x-tex">OR_1< / annotation>< / semantics>< / com:Math>, and <com:Math><semantics>T2<annotation encoding="application / x-tex">T_2< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>OR1<annotation encoding="application / x-tex">OR_1< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>OR2<annotation encoding="application / x-tex">OR_2< / annotation>< / semantics>< / com:Math>; or (ii) <com:Math><semantics>T1<annotation encoding="application / x-tex">T_1< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>OR1<annotation encoding="application / x-tex">OR_1< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>OR2<annotation encoding="application / x-tex">OR_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>T2<annotation encoding="application / x-tex">T_2< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>OR1<annotation encoding="application / x-tex">OR_1< / annotation>< / semantics>< / com:Math>: wherein preferably <com:Math><semantics>T1<annotation encoding="application / x-tex">T_1< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>OR1<annotation encoding="application / x-tex">OR_1< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>OR2<annotation encoding="application / x-tex">OR_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>T2<annotation encoding="application / x-tex">T_2< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>OR1<annotation encoding="application / x-tex">OR_1< / annotation>< / semantics>< / com:Math>. The compound of formula (II) is an alpha anomer or an alpha anomeric monomer that differs from the beta anomer in the spatial configuration of Bx at the chiral center of the first carbon at the 1' terminus. In another preferred embodiment, said compound of formula (I) is a compound of formula (III) [Image disponible dans le document PDF, Image available in the PDF document] (III) wherein (i) <com:Math><semantics>T1<annotation encoding="application / x-tex">T_1< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>OR1<annotation encoding="application / x-tex">OR_1< / annotation>< / semantics>< / com:Math>, and <com:Math><semantics>T2<annotation encoding="application / x-tex">T_2< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>OR1<annotation encoding="application / x-tex">OR_1< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>OR2<annotation encoding="application / x-tex">OR_2< / annotation>< / semantics>< / com:Math>; or (ii) <com:Math><semantics>T1<annotation encoding="application / x-tex">T_1< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>OR1<annotation encoding="application / x-tex">OR_1< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>OR2<annotation encoding="application / x-tex">OR_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>T2<annotation encoding="application / x-tex">T_2< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>OR1<annotation encoding="application / x-tex">OR_1< / annotation>< / semantics>< / com:Math>: wherein preferably <com:Math><semantics>T1<annotation encoding="application / x-tex">T_1< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>OR1<annotation encoding="application / x-tex">OR_1< / annotation>< / semantics>< / com:Math>, and <com:Math><semantics>T2<annotation encoding="application / x-tex">T_2< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>OR1<annotation encoding="application / x-tex">OR_1< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>OR2<annotation encoding="application / x-tex">OR_2< / annotation>< / semantics>< / com:Math>. The compound of formula (III) is a beta anomer or a beta anomeric monomer that differs from the alpha anomer in the spatial configuration of Bx at the chiral center of the first carbon at the 1' terminus. In another preferred embodiment, in the compound of formula (I), said phosphorus moiety R<com:Sub>2< / com:Sub> is selected from a phosphate moiety, a phosphoramidate moiety and a phosphoramidite moiety. In another preferred embodiment, in the compound of formula (II) said phosphorus moiety R<com:Sub>2< / com:Sub> is selected from a phosphate moiety, a phosphoramidate moiety and a phosphoramidite moiety. In another preferred embodiment, in the compound of formula (III) said phosphorus moiety R<com:Sub>2< / com:Sub> is selected from a phosphate moiety, a phosphoramidate moiety and a phosphoramidite moiety. In another preferred embodiment, in the compound of formula (I), (II) or (III) said Bx is selected from a purine base or pyrimidine base, wherein preferably Bx is selected from (i) adenine (A), (ii) cytosine (C), (iii) 5-methylcytosine (MeC), (iv) guanine (G), (v) uracil (U), or (vi) 5-methyluracil (MeU), or a derivative of (i), (ii), (iii), (iv), (v) or (vi), and wherein further preferably Bx is selected from uracil, thymine, cytosine, 5-methylcytosine, adenine or guanine. Again more preferably, in the compound of formula (I), (II) or (III), Bx is selected from thymine, 5-methylcytosine, adenine or guanine. In another preferred embodiment, the compound of formula (I), (II) or (III) is linked to a non-nucleosidic compound, preferably a solid-phase. In a preferred embodiment, the compound of formula (I) is selected from: [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] Z : [Image disponible dans le document PDF, Image available in the PDF document] ٠ In a second aspect, the invention provides an oligomer comprising at least one compound of formula (IV) [Image disponible dans le document PDF, Image available in the PDF document] (IV) wherein independently for each of said at least one compound of formula (IV) one of T<com:Sub>3< / com:Sub> or T<com:Sub>4< / com:Sub> is a nucleosidic linkage group; the other of T<com:Sub>3< / com:Sub> and T<com:Sub>4< / com:Sub> is OR<com:Sub>1< / com:Sub>, OR<com:Sub>2< / com:Sub>, a 5' terminal group, a 7' terminal group or a nucleosidic linkage group, wherein R<com:Sub>1< / com:Sub> is H or a hydroxyl protecting group, and R<com:Sub>2< / com:Sub> is a phosphorus moiety; and Bx is a nucleobase. In a preferred embodiment, the oligomer of the invention comprises at least one compound of formula (IV), wherein said compound of formula (IV) is a compound of formula (V): [Image disponible dans le document PDF, Image available in the PDF document] V) wherein (i) T<com:Sub>3< / com:Sub> is a nucleosidic linkage group, and T<com:Sub>4< / com:Sub> is a 7' terminal group, OR<com:Sub>1< / com:Sub>, or OR<com:Sub>2< / com:Sub>, preferably T<com:Sub>4< / com:Sub> is a 7' terminal group or OR<com:Sub>1< / com:Sub>; or (ii) <com:Math><semantics>T3<annotation encoding="application / x-tex">T_3< / annotation>< / semantics>< / com:Math> is a 5' terminal group, <com:Math><semantics>OR1<annotation encoding="application / x-tex">OR_1< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>OR2<annotation encoding="application / x-tex">OR_2< / annotation>< / semantics>< / com:Math>, preferably <com:Math><semantics>T3<annotation encoding="application / x-tex">T_3< / annotation>< / semantics>< / com:Math> is a 5' terminal group or <com:Math><semantics>OR2<annotation encoding="application / x-tex">OR_2< / annotation>< / semantics>< / com:Math>; and T<com:Sub>4< / com:Sub> is a nucleosidic linkage group; or (iii) <com:Math><semantics>T3<annotation encoding="application / x-tex">T_3< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>T4<annotation encoding="application / x-tex">T_4< / annotation>< / semantics>< / com:Math> are independently of each other a nucleosidic linkage group. In another preferred embodiment, the oligomer of the invention comprises at least one compound of formula (IV), wherein said compound of formula (IV) is a compound of formula (VI): [Image disponible dans le document PDF, Image available in the PDF document] (VI) wherein (i) T<com:Sub>3< / com:Sub> is a nucleosidic linkage group, and T<com:Sub>4< / com:Sub> is a 7' terminal group, OR<com:Sub>1< / com:Sub>, or OR<com:Sub>2< / com:Sub>, preferably T<com:Sub>4< / com:Sub> is a 7' terminal group or OR<com:Sub>2< / com:Sub>; or (ii) T<com:Sub>3< / com:Sub> is a 5' terminal group, OR<com:Sub>1< / com:Sub>, or OR<com:Sub>2< / com:Sub>, preferably T<com:Sub>3< / com:Sub> is a 5' terminal group or OR<com:Sub>1< / com:Sub>; and T<com:Sub>4< / com:Sub> is a nucleosidic linkage group; or (iii) <com:Math><semantics>T3<annotation encoding="application / x-tex">T_3< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>T4<annotation encoding="application / x-tex">T_4< / annotation>< / semantics>< / com:Math> are independently of each other a nucleosidic linkage group. In a preferred embodiment, said oligomer is an oligonucleotide. In a further preferred embodiment, said oligomer is an oligonucleotide, wherein said compound of formula (IV) is a compound of formula (V). In another preferred embodiment, said oligomer is an oligonucleotide, wherein said compound of formula (IV) is a compound of formula (VI). In a more preferred embodiment, the oligomer comprising said least one compound of formula (IV), (V) or (VI) is a DNA. In another embodiment, the inventive oligomer comprising said least one compound of formula (IV), (V) or (VI) further comprises at least one nucleotide that is different from any one of the compound of formula (IV), (V) or (VI), wherein preferably the at least one different nucleotide is (i) a nucleotide comprising a monocyclic sugar, i.e. a monocyclic nucleotide, or (ii) a nucleotide comprising a bicyclic sugar, i.e. a bicyclic nucleotide, or (iii) a nucleotide comprising a tricyclic sugar, i.e. a tricyclic nucleotide. Preferably, said at least one nucleotide that is different from the compound of formula (IV), (V) or (VI) is a nucleotide comprising a bicyclic sugar. Preferably, said at least one nucleotide that is different from the compound of formula (IV), (V) or (VI) is a nucleotide comprising a tricyclic sugar. More preferably, said at least one nucleotide that is different from the compound of formula (IV), (V) or (VI) is a nucleotide comprising a monocyclic sugar. In another preferred embodiment of the inventive oligomer, said compound of formula (IV) is a compound of formula (V), and said oligomer further comprises at least one nucleotide that is different from the compound of formula (V), wherein preferably the at least one different nucleotide is (i) a nucleotide comprising a monocyclic sugar, i.e. a monocyclic nucleotide, or (ii) a nucleotide comprising a bicyclic sugar, i.e. a bicyclic nucleotide, or (iii) a nucleotide comprising a tricyclic sugar, i.e. a tricyclic nucleotide. Preferably, said at least one nucleotide that is different from the compound of formula (V) is a nucleotide comprising a bicyclic sugar. Preferably, said at least one nucleotide that is different from the compound of formula (V) is a nucleotide comprising a tricyclic sugar. More preferably, said at least one nucleotide that is different from the compound of formula (V) is a nucleotide comprising a monocyclic sugar. In another preferred embodiment of the inventive oligomer, said compound of formula (IV) is a compound of formula (VI), and said oligomer further comprises at least one nucleotide that is different from the compound of formula (VI), wherein preferably the at least one different nucleotide is (i) a nucleotide comprising a monocyclic sugar, i.e. a monocyclic nucleotide, or (ii) a nucleotide comprising a bicyclic sugar, i.e. a bicyclic nucleotide, or (iii) a nucleotide comprising a tricyclic sugar, i.e. a tricyclic nucleotide. Preferably, said at least one nucleotide that is different from the compound of formula (VI) is a nucleotide comprising a bicyclic sugar. Preferably, said at least one nucleotide that is different from the compound of formula (VI) is a nucleotide comprising a tricyclic sugar. More preferably, said at least one nucleotide that is different from the compound of formula (VI) is a nucleotide comprising a monocyclic sugar. In another embodiment, the oligomer comprising the compound of formula (IV), (V) or (VI) further comprises at least two nucleotides that are different from the compound of formula (IV), (V) or (VI), wherein said at least two different nucleotides are linked to each other by a nucleosidic linkage group, wherein each nucleosidic linkage group is independently of each other selected from a phosphodiester linkage group, a phosphotriester linkage group, a phosphorothioate linkage group, a phosphorodithioate linkage group, a phosphonate linkage group, a phosphonothioate linkage group, a phosphinate linkage group, a phosphorthioamidate linkage or a phosphoramidate linkage group, and wherein preferably each nucleosidic linkage group is independently of each other a phosphodiester linkage group or a phosphorothioate linkage group, and wherein further preferably each nucleosidic linkage group is a phosphorothioate linkage group. In another preferred embodiment of the inventive oligomer, said compound of formula (IV) is a compound of formula (V), and said oligomer further comprises at least two nucleotides that are different from the compound of formula (V), wherein said at least two different nucleotides are linked to each other by a nucleosidic linkage group, wherein each nucleosidic linkage group is independently of each other selected from a phosphodiester linkage group, a phosphotriester linkage group, a phosphorothioate linkage group, a phosphorodithioate linkage group, a phosphonate linkage group, a phosphonothioate linkage group, a phosphinate linkage group, a phosphorthioamidate linkage or a phosphoramidate linkage group, and wherein preferably each nucleosidic linkage group is independently of each other a phosphodiester linkage group or a phosphorothioate linkage group, and wherein further preferably each nucleosidic linkage group is a phosphorothioate linkage group. In another preferred embodiment of the inventive oligomer, said compound of formula (IV) is a compound of formula (VI), and said oligomer further comprises at least two nucleotides that are different from the compound of formula (VI), wherein said at least two different nucleotides are linked to each other by a nucleosidic linkage group, wherein each nucleosidic linkage group is independently of each other selected from a phosphodiester linkage group, a phosphotriester linkage group, a phosphorothioate linkage group, a phosphorodithioate linkage group, a phosphonate linkage group, a phosphonothioate linkage group, a phosphinate linkage group, a phosphorthioamidate linkage or a phosphoramidate linkage group, and wherein preferably each nucleosidic linkage group is independently of each other a phosphodiester linkage group or a phosphorothioate linkage group, and wherein further preferably each nucleosidic linkage group is a phosphorothioate linkage group. In another preferred embodiment, in the oligomer of the invention, Bx is selected from a purine base or pyrimidine base, wherein preferably Bx is selected from (i) adenine (A), (ii) cytosine (C), (iii) 5-methylcytosine (MeC), (iv) guanine (G), (v) uracil (U), or (vi) 5- methyluracil (MeU), or a derivative of (i), (ii), (iii), (iv), (v) or (vi), and wherein further preferably Bx is selected from uracil, thymine, cytosine, 5-methylcytosine, adenine or guanine. More preferably, in the oligomer of the invention, Bx is selected from thymine, 5- methylcytosine, adenine or guanine. In another preferred embodiment, in the oligomer of the invention, each nucleosidic linkage group is independently of each other selected from a phosphodiester linkage group, a phosphotriester linkage group, a phosphorothioate linkage group, a phosphorodithioate linkage group, a phosphonate linkage group, a phosphonothioate linkage group, a phosphinate linkage group, a phosphorthioamidate linkage or a phosphoramidate linkage group, and wherein preferably each nucleosidic linkage group is independently of each other a phosphodiester linkage group or a phosphorothioate linkage group, and wherein further preferably each nucleosidic linkage group is a phosphorothioate linkage group. In another embodiment, the oligomer of the invention comprises 1 to 5, preferably 1 to 4, more preferably 1 to 2, again more preferably 1 to 2, again more preferably exactly one compound of formula (IV), (V) or (VI). In a preferred embodiment of the inventive oligomer, said compound of formula (IV) is a compound of formula (VI), and wherein said oligomer comprises 1 to 5, preferably 1 to 4, more preferably 1 to 2, again more preferably 1 to 2, again more preferably exactly one compound of formula (VI). It has been found that, in particular, a single incorporation of a compound of formula (VI) within an oligonucleotide, and preferably a single incorporation of a compound of formula (VI), wherein Bx is methylcytosine, inside DNA duplexes has a substantial stabilizing effect. Thus, in a very preferred embodiment of the inventive oligomer, said oligomer comprises exactly one compound of formula (IV), wherein said compound of formula (IV) is a compound of formula (VI) and wherein said Bx is methylcytosine, and wherein said oligomer is an oligonucleotide and further comprises at least one nucleotide that is different from the compound of formula (VI), wherein preferably the at least one different nucleotide is a nucleotide comprising a monocyclic sugar. In another preferred embodiment of the inventive oligomer, said oligomer comprises at least two compounds of formula (IV) and further comprises at least one nucleotide that is different from the compound of formula (IV), wherein said compound of formula (IV) is a compound of formula (V), and wherein EACH of said compound of formula (V) is linked with its 5' terminus to (i) a 5' terminus of said at least one nucleotide that is different from the compound of formula (IV) or (ii) a 7' terminus of another compound of formula (V); and wherein said compound of formula (V) is linked with its 7' terminus to (i) a 3' terminus of said at least one nucleotide that is different from the compound of formula (IV) or (ii) a 5' terminus of another compound of formula (V). In another embodiment of the inventive oligomer, said oligomer comprises at least two compounds of formula (IV) and further comprises at least one nucleotide that is different from the compound of formula (IV), wherein said compound of formula (IV) is a compound of formula (VI), and wherein EACH of said compound of formula (VI) is linked with its 5' terminus to (i) a 3' terminus of said at least one nucleotide that is different from the compound of formula (IV) or (ii) a 3' terminus of another compound of formula (VI); and wherein EACH of said compound of formula (VI) is linked with its 3' terminus to (i) a 5' terminus of said at least one nucleotide that is different from the compound of formula (IV) or (ii) a 5' terminus of another compound of formula (VI). In a preferred embodiment of the inventive oligomer, said oligomer further comprises at least two nucleotides that are different from the compound of formula (IV), and wherein said compound of formula (IV) is a compound of formula (V), and wherein EACH OF said nucleotide that is different from the compound of formula (IV) is linked with its 3' terminus to (i) a 7' terminus of said compound of formula (V) or (ii) a 5' terminus of another nucleotide that is different from the compound of formula (IV), and wherein EACH of said nucleotide that is different from the compound of formula (IV) is linked with its 5' terminus to (i) a 5' terminus of said compound of formula (V) or (ii) a 3' terminus of another nucleotide that is different from the compound of formula (IV). In a preferred embodiment of the inventive oligomer, said oligomer further comprises at least two nucleotides that are different from the compound of formula (IV), and wherein said compound of formula (IV) is a compound of formula (V), and wherein EACH of said nucleotide that is different from the compound of formula (IV) is linked with its 3' terminus to (i) a 7' terminus of said compound of formula (V) or (ii) a 5' terminus of another nucleotide that is different from the compound of formula (IV), and wherein EACH of said nucleotide that is different from the compound of formula (IV) is linked with its 5' terminus to (i) a 5' terminus of said compound of formula (V) or (ii) a 3' terminus of another nucleotide that is different from the compound of formula (IV). In a preferred embodiment of the inventive oligomer, said oligomer further comprises at least two nucleotides that are different from the compound of formula (IV), and wherein said compound of formula (IV) is a compound of formula (V), and wherein each of the at least one compound of formula (V) is linked with its 5' terminus and with its 7' terminus to said nucleotide that is different from the compound of formula (IV). In a preferred embodiment of the inventive oligomer, said oligomer further comprises at least two nucleotides that are different from the compound of formula (IV), and wherein said compound of formula (IV) is a compound of formula (V), and wherein EACH of said nucleotide that is different from the compound of formula (IV) is linked with its 3' terminus to (i) a 7' terminus of said compound of formula (V) or (ii) a 5' terminus of another nucleotide that is different from the compound of formula (IV), and wherein EACH of said nucleotide that is different from the compound of formula (IV) is linked with its 5' terminus to (i) a 5' terminus of said compound of formula (V) or (ii) a 3' terminus of another nucleotide that is different from the compound of formula (IV). In a preferred embodiment of the inventive oligomer, said oligomer further comprises at least two nucleotides that are different from the compound of formula (IV), and wherein said compound of formula (IV) is a compound of formula (VI), and wherein each of the at least one compound of formula (VI) is linked with its 5' terminus and with its 7' terminus to said nucleotide that is different from the compound of formula (IV). In another preferred embodiment of the inventive oligomer, said oligomer comprises at least two compounds of formula (IV) and further comprises at least two nucleotides that are different from the compound of formula (IV), and wherein said compound of formula (IV) is a compound of formula (V), and wherein each of the at least one compound of formula (V) is linked with its 7' terminus to a 3' terminus of the nucleotide that is different from the compound of formula (IV); and with its 5' terminus to a 5' terminus of a nucleotide that is different from the compound of formula (IV). In another preferred embodiment of the inventive oligomer, said oligomer comprises at least two compounds of formula (IV) and further comprises at least two nucleotides that are different from the compound of formula (IV), and wherein said compound of formula (IV) is a compound of formula (VI), and wherein each of the at least one compound of formula (VI) is linked with its 5' terminus to a 3' terminus of the nucleotide that is different from the compound of formula (IV); and with its 7' terminus to a 5' terminus of a nucleotide that is different from the compound of formula (IV). In a preferred embodiment of the inventive oligomer, said oligomer comprises at least one compound of formula (IV), wherein said compound is a compound of formula (VI), wherein each of the at least one compound of formula (VI) is linked with its 5' terminus and with its 7' terminus to a nucleotide that is different from the compound of formula (IV), and wherein Bx is cytosine or 5-methylcytosine, preferably 5-methylcytosine. In a further preferred embodiment of the inventive oligomer, said oligomer comprises exactly one compound of formula (IV), wherein said compound is a compound of formula (VI), wherein said compound of formula (VI) is linked with its 5' terminus and with its 7' terminus to a nucleotide that is different from the compound of formula (IV), and wherein Bx is cytosine or 5-methylcytosine, preferably 5-methylcytosine. In another preferred embodiment, the oligomer of the invention comprises 1 to 5, preferably 1 to 4, more preferably 1 to 2, again more preferably 1 to 2, again more preferably exactly one compound of formula (IV), (V) or (VI), preferably of formula (VI), wherein Bx is a pyrimidine base, more preferably cytosine or 5-methylcytosine, again more preferably 5- methylcytosine. In a more preferred embodiment, the oligomer of the invention comprises exactly one compound of formula (VI), wherein Bx is cytosine or 5-methylcytosine, preferably 5-methylcytosine. Incorporation of exactly one or only few compounds of formula (IV), (V) or (VI), preferably of formula (VI), wherein Bx is a pyrimidine bases, leads only to a small destabilization or even stabilizes duplex formation with oligomers of the invention. Especially, when the nucleobase is a cytosine or cytosine derivative, preferably 5- methylcytosine, significantly stabilize duplexes of the oligomer of the invention including compounds of formula (IV), (V) or (VI), preferably of formula (VI), with complementary DNA. This stabilizing effect is more pronounced for the 5-methyl cytosine nucleosides. In another embodiment, the oligomer of the invention comprises 1 to 5, preferably 1 to 4, more preferably 1 to 2, again more preferably 1 to 2, again more preferably exactly one compound of formula (IV), (V) or (VI), preferably of formula (VI), wherein Bx is a purine base. The nucleobase purine stabilizes duplexes of the oligomers of the invention including compounds of formula (IV), (V) or (VI), preferably of formula (VI), with complementary RNA. In another preferred embodiment, the oligomer of the invention comprises or preferably consists of at least two contiguous compounds of formula (IV), wherein each of the contiguous compounds of formula (IV) is independently linked to the adjacent contiguous compound of formula (IV) by the nucleosidic linkage group, wherein the nucleosidic linkage group links a 5' terminus and a 7' terminus of two contiguous compounds of formula (IV). In another preferred embodiment, in the oligomer of the invention comprises or preferably consists of at least two contiguous compounds of formula (V), wherein each of the contiguous compounds of formula (V) is independently linked to the adjacent contiguous compound of formula (V) by the nucleosidic linkage group, wherein the nucleosidic linkage group links a 5' terminus and a 7' terminus of two contiguous compounds of formula (V). In another preferred embodiment, in the oligomer of the invention comprises or preferably consists of at least two contiguous compounds of formula (VI), wherein each of the contiguous compounds of formula (VI) is independently linked to the adjacent contiguous compound of formula (VI) by the nucleosidic linkage group, wherein the nucleosidic linkage group links a 5' terminus and a 7' terminus of two contiguous compounds of formula (VI). In a further preferred embodiment, the oligomer of the invention comprises or preferably consists of 10 to 40 contiguous compounds of formula (IV), preferably 10 to 30 contiguous compounds of formula (IV), more preferably 10 to 25 contiguous compounds of formula (IV), again more preferably 10 to 20 contiguous compounds of formula (IV) or 10 to 15 contiguous compounds of formula (IV). In a further preferred embodiment of the inventive oligomer, said at least one compound of formula (IV) is a compound of formula (V), and wherein said oligomer comprises or preferably consists of 10 to 40 contiguous compounds of formula (V), preferably 10 to 30 contiguous compounds of formula (V), more preferably 10 to 25 contiguous compounds of formula (V), again more preferably 10 to 20 contiguous compounds of formula (V), and again more preferably 10 to 15 contiguous compounds of formula (V). In a further preferred embodiment of the inventive oligomer, said at least one compound of formula (IV) is a compound of formula (VI), and wherein said oligomer comprises or preferably consists of 10 to 40 contiguous compounds of formula (VI), preferably 10 to 30 contiguous compounds of formula (VI), more preferably 10 to 25 contiguous compounds of formula (VI), again more preferably 10 to 20 contiguous compounds of formula (VI), and again more preferably 10 to 15 contiguous compounds of formula (VI). In a further preferred embodiment of the inventive oligomer, said at least one compound of formula (IV) is a compound of formula (V), and wherein said oligomer comprises or preferably consists of 10 to 40 contiguous compounds of formula (V), preferably 10 to 30 contiguous compounds of formula (V), more preferably 10 to 25 contiguous compounds of formula (V), again more preferably 10 to 20 contiguous compounds of formula (V), and again more preferably 10 to 15 contiguous compounds of formula (V) and wherein each of the contiguous compounds of formula (V) is independently linked to the adjacent contiguous compound of formula (V) by the nucleosidic linkage group, wherein the nucleosidic linkage group links a 5' terminus and a 7' terminus of two contiguous compounds of formula (V), and wherein said nucleosidic linkage group is a phosphorus linkage group, and wherein said phosphorus linkage group is selected from a phosphodiester linkage group, a phosphotriester linkage group and a phosphorothioate linkage group, and wherein preferably said phosphorus linkage group is a phosphodiester linkage group or a phosphorothioate linkage group. In a further preferred embodiment, the oligomer of the invention comprises or preferably consists of at least one nucleic acid sequence, wherein said nucleic acid sequence comprises said at least one compound of formula (IV), and wherein said nucleic acid sequence is selected from SEQ ID NO: 1 to 24, preferably SEQ ID NO: 24. In a further preferred embodiment, the oligomer of the invention comprises or preferably consists of at least one nucleic acid sequence, wherein said nucleic acid sequence comprises said at least one compound of formula (V), and wherein said nucleic acid sequence is selected from SEQ ID NO: 16 to 24, preferably SEQ ID NO: 21 to 24, more preferably SEQ ID NO: 24. In a further preferred embodiment, the oligomer of the invention comprises or preferably consists of at least one nucleic acid sequence, wherein said nucleic acid sequence comprises said at least one compound of formula (VI), and wherein said nucleic acid sequence is selected from SEQ ID NO: 1 to 15, preferably SEQ ID NO: 13-15. In a more preferred embodiment, the oligomer of the invention consists of a nucleic acid sequence selected from SEQ ID NO: 13 to 15 or 21 to 24, preferably SEQ ID NO: 24. In another preferred embodiment, said oligomer is the nucleic acid sequence selected from SEQ ID NO: 13 to 15 or 21 to 24, and wherein preferably said oligomer is SEQ ID NO: 24. In a further preferred embodiment of the inventive oligomer, said oligomer comprises a nucleic acid sequence, wherein said nucleic acid sequence consists of at least two contiguous compounds of formula (IV), wherein said nucleic acid sequence is flanked on its 5' terminus or its 7' terminus by at least one nucleotide or nucleoside that is different from the compound of formula (IV). In a further preferred embodiment of the inventive oligomer, said oligomer comprises a nucleic acid sequence, wherein said nucleic acid sequence consists of at least two contiguous compounds of formula (V), wherein said nucleic acid sequence is flanked on its 5' terminus or its 7' terminus by at least one nucleotide or nucleoside that is different from the compound of formula (V), preferably different from the compound of formula (V) or (VI), and further preferably different from the compound of formula (IV). In a further preferred embodiment of the inventive oligomer, said, oligomer comprises a nucleic acid sequence, wherein said nucleic acid sequence consists of at least two contiguous compounds of formula (VI), wherein said nucleic acid sequence is flanked on its 5' terminus or its 7' terminus by at least one nucleotide or nucleoside that is different from the compound of formula (VI), preferably different from the compound of formula (V) or (VI), and further preferably different from the compound of formula (IV). In a further preferred embodiment of the inventive oligomer, said oligomer comprises a nucleic acid sequence, wherein said nucleic acid sequence consists of at least two contiguous compounds of formula (IV), wherein said nucleic acid sequence is flanked on its 5' terminus and its 7' terminus by at least one nucleotide or nucleoside that is different from the compound of formula (IV). In a further preferred embodiment of the inventive oligomer, said oligomer comprises a nucleic acid sequence, wherein said nucleic acid sequence consists of at least two contiguous compounds of formula (V), wherein said nucleic acid sequence is flanked on its 5' terminus and its 7' terminus by at least one nucleotide or nucleoside that is different from the compound of formula (V), preferably different from the compound of formula (V) or (VI), and further preferably different from the compound of formula (IV). In a further preferred embodiment of the inventive oligomer, said oligomer comprises a nucleic acid sequence, wherein said nucleic acid sequence consists of at least two contiguous compounds of formula (VI), wherein said nucleic acid sequence is flanked on its 5' terminus and its 7' terminus by at least one nucleotide or nucleoside that is different from the compound of formula (VI), preferably different from the compound of formula (V) or (VI), and further preferably different from the compound of formula (IV). In a further preferred embodiment of the inventive oligomer, said oligomer comprises a nucleic acid sequence, wherein said nucleic acid sequence consists of at least two contiguous compounds of formula (V), wherein said nucleic acid sequence is flanked on its 5' terminus or its 7' terminus by at least one nucleotide or nucleoside that is different from the compound of formula (V), preferably different from the compound of formula (V) or (VI), and further preferably different from the compound of formula (IV), wherein the 5' terminus of said nucleic acid sequence is linked to a 5' terminus of the nucleotide that is different from the compound of formula (V), preferably different from the compound of formula (V) or (VI), and further preferably different from the compound of formula (IV); or wherein the 7' terminus of said nucleic acid sequence is linked to a 3' terminus of the nucleotide or nucleoside that is different from the compound of formula (V), preferably different from the compound of formula (V) or (VI), and further preferably different from the compound of formula (IV). In a further preferred embodiment of the inventive oligomer, said oligomer comprises a nucleic acid sequence, wherein said nucleic acid sequence consists of at least two contiguous compounds of formula (V), wherein said nucleic acid sequence is flanked on its 5' terminus and on its 7' terminus by at least one nucleotide or nucleoside that is different from the compound of formula (V), preferably different from the compound of formula (V) or (VI), and further preferably different from the compound of formula (IV), wherein the 5' terminus of said nucleic acid sequence is linked to a 5' terminus of the nucleotide or nucleoside that is different from the compound of formula (V), preferably different from the compound of formula (V) or (VI), and further preferably different from the compound of formula (IV); and wherein the 7' terminus of said nucleic acid sequence is linked to a 3' terminus of the nucleotide or nucleoside that is different from the compound of formula (V), preferably different from the compound of formula (V) or (VI), and further preferably different from the compound of formula (IV). In a further preferred embodiment of the inventive oligomer, said oligomer comprises a nucleic acid sequence, wherein said nucleic acid sequence consists of at least two contiguous compounds of formula (VI), wherein said nucleic acid sequence is flanked on its 5' terminus or on its 7' terminus by at least one nucleotide or nucleoside t that is different from the compound of formula (VI), preferably different from the compound of formula (V) or (VI), and further preferably different from the compound of formula (IV), wherein the 5' terminus of said nucleic acid sequence is linked to a 3' terminus of the nucleotide or nucleoside that is different from the compound of formula (VI), preferably different from the compound of formula (V) or (VI), and further preferably different from the compound of formula (IV); or wherein the 7' terminus of said nucleic acid sequence is linked to a 5' terminus of the nucleotide or nucleoside that is different from the compound of formula (VI), preferably different from the compound of formula (V) or (VI), and further preferably different from the compound of formula (IV). In a further preferred embodiment of the inventive oligomer, said oligomer comprises a nucleic acid sequence, wherein said nucleic acid sequence consists of at least two contiguous compounds of formula (VI), wherein said nucleic acid sequence is flanked on its 5' terminus and on its 7' terminus each by at least one nucleotide or nucleoside that is different from the compound of formula (VI), preferably different from the compound of formula (V) or (VI), and further preferably different from the compound of formula (IV), wherein the 5' terminus of said nucleic acid sequence is linked to a 3' terminus of the nucleotide or nucleoside that is different from the compound of formula (VI), preferably different from the compound of formula (V) or (VI), and further preferably different from the compound of formula (IV); and wherein the 7' terminus of said nucleic acid sequence is linked to a 5' terminus of the nucleotide or nucleoside that is different from the compound of formula (VI), preferably different from the compound of formula (V) or (VI), and further preferably different from the compound of formula (IV). In a further preferred embodiment of the inventive oligomer, said compound of formula (IV) is selected from [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] In a further preferred embodiment, the oligomer of the invention is double-stranded. In a certain embodiment, exactly one or both strands of said double stranded oligomer comprise at least one compound of formulae (IV), (V) or (VI). In a third aspect, the present invention provides the inventive compound of formula (I), (II) or (III) or the oligomer of the invention for use as a medicament in the prevention, treatment or diagnosis of a disease. In a certain embodiment, the compound of formula (I), (II) or (III) is used as a medicament in the prevention or treatment of a disease. The invention provides a method of preventing a disease in a patient or treating a patient suffering from a disease by administering a therapeutically effective amount of formula (I), (II) or (III) to the patient. In another embodiment, the compound of formula (I), (II) or (III) is used for the manufacture of a medicament for the prevention or treatment of a disease. In a further embodiment, the oligomer of the invention is used as a medicament in the prevention or treatment of a disease. The invention provides a method of preventing a disease in a patient or treating a patient suffering from a disease by administering a therapeutically effective amount of the oligomer of the invention to the patient. In another preferred embodiment, the oligomer of the invention is used for the manufacture of a medicament for the prevention or treatment of a disease. The term "patient" as used herein refers to a human or an animal, wherein the animal is preferably a mammal. The term "patient" is not restricted to subjects showing symptoms of a disease or disorder, but includes healthy subjects (i.e. without symptoms) or subjects being at risk for exhibiting a symptom. A "therapeutically effective amount" refers to an amount administered to a subject, either as a single dose or as part of a series of doses, which is effective to produce a desired physiological response or therapeutic effect in the subject. Examples of desired therapeutic effects include, without limitation, improvements in the symptoms or pathology, reducing the progression of symptoms or pathology, and slowing the onset of symptoms or pathology of the disease. The therapeutically effective amount will vary depending on the nature of the formulation used and the type and condition of the recipient. The determination of appropriate amounts for any given composition is within the skill in the art, through standard series of tests designed to assess appropriate therapeutic levels. Typical and preferred therapeutically effective amounts of the antisense oligonucleotide range from about 0.05 to 1000 mg / kg body weight, and in particular from about 5 to 500 mg / kg body weight. In a further embodiment, the oligomer of the invention is an antisense oligonucleotide. In preferred embodiment the antisense oligonucleotide of the invention is used in the prevention, treatment or diagnosis of a disease. As used herein, the term "antisense oligonucleotide" refers to an oligonucleotide that is capable of hybridizing with a target nucleic acid sequence. In a preferred embodiment, the antisense oligonucleotide is complementary to the target nucleic acid sequence. An oligonucleotide is complementary to a target nucleic acid when a sufficient number of complementary positions in the oligonucleotide and the target nucleic acid are occupied by complementary nucleobases which can form hydrogen bonds with each other such that specific binding occurs between the oligonucleotide and the target nucleic acid. For example, adenine and thymine are complementary nucleobases which pair through the formation of hydrogen bonds. Hybridization can occur under varying circumstances. It is understood in the art that the sequence of an antisense oligonucleotide need not to include nucleotides that are 100% complementary to the nucleotides of the target nucleic acid to be hybridizable. An antisense oligonucleotide may hybridize over one or more nucleotides whereas intervening or adjacent nucleotides are not involved in hybridization. It is preferred that the oligonucleotide portion of the antisense oligonucleotide of the present invention comprise at least 70% sequence complementarity to a target region within the target nucleic acid, more preferably that they comprise 85% or 90% sequence complementarity, and even more preferably comprise 95% sequence complementarity to the target region within the target nucleic acid sequence. In a certain embodiment, the oligomer of the invention is used in the prevention or treatment of a disease, wherein the oligomer is capable of interfering with replication, translation, transcription, translocation, catalytic acitivity, complex formation, splicing or integrity of a target nucleic acid. In a certain embodiment, the oligomer of the invention is used in the prevention or treatment of a disease, wherein the oligomer is capable of binding to a target nucleic acid, downregulating expression of a target nucleic acid, sterically blocking a target nucleic acid sequence or inducing nucleic acid interference, gene silencing, degradation or exon skipping in a target nucleic acid. In a preferred embodiment, the oligomer of the invention is used in the prevention or treatment of a disease, wherein the oligomer is capable of binding to a target nucleic acid and downregulating expression of said target nucleic acid. In another preferred embodiment, the oligomer of the invention is used in the prevention or treatment of a disease, wherein the oligomer is capable of binding to a target nucleic acid, sterically blocking said target nucleic acid and inducing exon skipping in said target nucleic acid. In a preferred embodiment, said target nucleic acid is a DNA or RNA. The RNA is preferably a pre-mRNA (pre-processed or precursor messenger RNA) or mature RNA. The RNA can be an mRNA or a functional form of a non-coding RNA, such as a long non-coding RNA, micro RNA, small interfering RNA, small nucleolar RNA, Piwi-interacting RNA, tRNA-derived small RNA, small rDNA-derived RNA, rRNA or tRNA. In a certain embodiment, the oligomer of the invention is used in the prevention or treatment of a disease, wherein the oligomer is capable of altering a splice process in a target nucleic acid, wherein preferably the target nucleic acid is a pre-mRNA. Preferably said oligomer is capable of inducing exon skipping in a target pre-mRNA. An "exon" refers to a defined section of a nucleic acid that encodes for a protein, or a nucleic acid sequence that is represented in the mature form of an RNA molecule after either portions of a pre-mRNA have been removed by splicing. In a further embodiment, the oligomer of the invention is used as a medicament in the prevention or treatment of a disease, wherein said disease is a genetic disease. In a preferred embodiment, the oligomer of the invention is used as a medicament in the prevention or treatment of a disease, wherein said disease is a muscular dystrophy, preferably Duchenne muscular dystrophy. In another preferred embodiment, the oligomer for use as a medicament in the prevention, treatment or diagnosis of a disease is the nucleic acid sequence of SEQ ID NO: 21 or the nucleic acid sequence of SEQ ID NO: 24, preferably the nucleic acid sequence of SEQ ID NO: 24 and wherein the disease is a muscular dystrophy, preferably Duchenne muscular dystrophy. The oligomers of the invention and in particular SEQ ID NO: 24 maintain a good affinity toward RNA, and oligomers consisting of compounds of formula (V) seem to confer a significantly improved biostability compared to its naturally occurring corresponding DNA. Moreover, the nucleic acid of SEQ ID NO: 24 does not activate complement significantly, and complement activation represents an important toxic response often associated with an in vivo use of antisense oligonucleotides. Therefore, the oligomers of the invention, preferably oligomers comprising or preferably consisting of compounds of formula (V) are promising antisense candidates. Finally, oligomers consisting of compounds of formula (V), preferably the nucleic acid of SEQ ID NO: 24 is able to induce strong exon skipping of exon 23 and double exon skipping of exons 22 and 23. These promising results indicate that the oligomer of the invention, especially oligomers consisting of compounds of formula (V) meet the prerequisites to induce a strong therapeutic effect in patients suffering muscular dystrophies, such as Duchenne. In another aspect, the present invention provides for the oligomer of the invention for use as a medicament in the prevention or treatment of a disease. In a further aspect, the oligomer of the invention is used in the diagnosis of a disease. In a further aspect, the oligomer of the invention is used as a medicament in the diagnosis of a disease. In another preferred embodiment, the oligomer of the invention is used for the manufacture of a medicament for the diagnosis of a disease. The invention provides a method of diagnosing a disease in a patient. Said diagnosis or said diagnosing comprises (i) administering an effective amount of the oligomer of the invention to a patient, wherein the oligomer is labelled, and (ii) non-invasive or invasive, preferably non-invasive in vivo imaging of the labelled oligomer or (i') obtaining a sample from a patient, (ii') adding a oligomer of the invention to the sample, wherein the oligomer is labelled, and (iii') analyzing the sample for binding of the labelled oligomer with nucleic acids included in the sample. In a preferred embodiment, the oligomer of the invention used in the diagnosis of a disease is an oligonucleotide, more preferably an antisense oligonucleotide. The sample obtained from a patient is preferably a blood, serum, liquor or tissue sample. The term "labelled oligomer" as used herein refers to an oligomer comprising a label. Preferably the label is selected from a fluorescent label, dye, reporter group or a radiolabel. In a further aspect, the invention provides a pharmaceutical composition comprising at least one compound selected from formula (I), (II) or (III). In a further aspect, the invention provides a pharmaceutical composition comprising at least one oligomer of the invention. In a preferred embodiment, said pharmaceutical composition comprises one or more oligomers of the invention, wherein at least one of said one or more oligomers is an oligonucleotide, more preferably an antisense oligonucleotide. In a preferred embodiment, the pharmaceutical composition comprises a therapeutically-effective amount of the at least one compound of formula (I), (II) or (III) or the at least one oligomer of the invention, preferably formulated together with one or more pharmaceutically acceptable carriers. In one embodiment, a unit dose of the pharmaceutical composition of the invention contains about 1 microgram to 20,000 micrograms of the oligomer or the compound of formula (I), (II) or (III) per unit, and preferably from about 10 to 1000 micrograms. For intravenous delivery, a unit dose of the pharmaceutical formulation contains preferably from 0.5 to 500 micrograms per kg body weight, more preferably from 5 to 300 micrograms per kg body weight of the oligomer of the invention. In the pharmaceutical compositions of the invention, the oligomer or the compound of formula (I), (II) or (III) is ordinarily present in an amount of about 0.5-95% by weight based on the total weight of the composition. In a preferred embodiment, the pharmaceutical composition comprising the at least one compound of formula (I), (II) or (III) or the at least one oligomer of the invention further comprises at least one pharmaceutically acceptable carrier. The term "pharmaceutically acceptable carrier" as used herein means a pharmaceutically acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, manufacturing aid (e.g., lubricant, tale magnesium, calcium or zine stearate, or steric acid), or solvent encapsulating material. The pharmaceutically acceptable carrier can be involved in carrying or transporting the subject compound from one organ or portion of the body to another. Methods for the delivery of nucleic acids are described, for example, in Akhtar et al., 1992, Trends Cell Bio., 2:139; and Delivery Strategies for Antisense Oligonucleotide Therapeutics, ed. Akhtar; Sullivan et al., PCT WO 94 / 02595. These and other protocols can be utilized for the delivery of virtually any nucleotide or nucleic acid molecule, including the compound of formula (I), (II) or (III) and the oligomers of the present invention. The invention also features the pharmaceutical composition of the invention further comprising P-glycoprotein inhibitors (such as Pluronic P85), which can enhance entry of drugs into various tissues; biodegradable polymers, such as poly (DL-lactide-coglycolide) microspheres for sustained release delivery after implantation (Emerich, DF et al., 1999, Cell Transplant, 8, 47-58) Alkermes, Inc. Cambridge, Mass); nanoparticles, such as those made of polybutylcyanoacrylate, which can deliver drugs across the blood brain barrier and can alter cellular uptake mechanisms (Prog Neuropsychopharmacol Biol Psychiatry, 23, 941-949, 1999); or liposomes containing polyethylene glycol-lipids. Administration of the pharmaceutical composition, the compound of formula (I), (II) or (III) or the oligomer of the invention can be carried out using the various mechanisms known in the art. In a preferred embodiment, the pharmaceutical composition, the compound of formula (I), (II) or (III) or the oligomer of the invention is administered locally or systemically. In a preferred embodiment, the pharmaceutical composition, the compound of formula (I), (II) or (III) or the oligomer of the invention is administered orally (for example, as an aqueous or non-aqueous solution or suspension, tablet, bolus, powder, granule, paste), parenterally (for example, by subcutaneous, intramuscular, intravenous, intraperitoneal or epidural injection as, for example, a sterile solution or suspension, or sustained-release formulation), topically (for example, as a cream, ointment, or a controlled-release patch or spray), intravaginally or intrarectally (for example, as a pessary, cream or foam), sublingually, ocularly, transdermally, nasally, intracellularly or by direct local tumor injection. In a preferred embodiment, the pharmaceutical composition comprising the oligomer of the invention is used for downregulating expression of a target nucleic acid, sterically blocking a target nucleic acid sequence or inducing nucleic acid interference, gene silencing, degradation or exon skipping in a target nucleic acid. In a further aspect, the oligomer of the invention is used in vitro for binding to a target nucleic acid sequence. In a preferred embodiment, the oligomer of the invention is used in vitro for downregulating expression of a target nucleic acid, sterically blocking a target nucleic acid sequence or inducing nucleic acid interference, gene silencing, degradation or exon skipping in a target nucleic acid. In a certain embodiment, the oligomer of the invention is used in vitro for interfering with replication, translation, transcription, translocation, catalytic acitivity, complex formation, splicing or integrity of a target nucleic acid. In a preferred embodiment, oligomer of the invention is used in vitro for binding to a target nucleic acid, wherein exon skipping is induced in said target nucleic acid. In a preferred embodiment, the present invention provides an in vitro method of down-regulating the expression of a target gene in the cytosol of a cell by delivering the oligomer of the invention of the invention across a membrane of the cell. In a preferred embodiment, the target nucleic acid is DNA, pre-mRNA or mature mRNA. In a further aspect, the invention provides a method for solid-phase synthesis of an oligomer of the invention comprising the use of any one of the compounds of formulae (I) to (VI). EXAMPLES General procedures All reactions were performed in dried glassware and under an inert atmosphere of Argon. Anhydrous solvents for reactions were obtained by filtration through activated alumina or by storage over molecular sieves (4 Å). Colum chromatography (CC) was performed on silica gel (SiliaFlash P60, 40-63 um, 60 Å). Methanol used for CC was of HPLC grade, all other solvents used for CC were of technical grade and distilled prior to use. Thin-layer chromatography was performed on silica gel plates (macherey-nagel, pre-coated TLC-plates sil G-25 UV254). Compounds were visualized under UV-light or by dipping in a p-Anisaldehyde staining solution [p-Anisaldehyde (3.7 mL), glacial acetic acid (3.7 mL), concentrated sulfuric acid (5 mL), ethanol (135 mL)] followed by heating with a heat gun. NMR spectra were recorded at 300 or 400 MHz (<com:Sup>1< / com:Sup>H), at 75 or 101 MHz (<com:Sup>13< / com:Sup>C) and at 122 MHz (<com:Sup>31< / com:Sup>P) in either CDCl<com:Sub>3< / com:Sub>, CD<com:Sub>3< / com:Sub>OD or CD<com:Sub>3< / com:Sub>CN. Chemical shifts (δ) are reported relative to the residual undertreated solvent peak [CDCl<com:Sub>3< / com:Sub>: 7.26 ppm (<com:Sup>1< / com:Sup>H), 77.16 ppm (<com:Sup>13< / com:Sup>C); CD<com:Sub>3< / com:Sub>OD: 3.31 ppm (<com:Sup>1< / com:Sup>H), 49.00 ppm (<com:Sup>13< / com:Sup>C)]. Signal assignments are based APT and DEPT and on <com:Sup>1< / com:Sup>H, <com:Sup>1< / com:Sup>H and <com:Sup>1< / com:Sup>H, <com:Sup>13< / com:Sup>C correlation experiments (COSY, HSQC, HMBC). High resolution mass detections were performed by electrospray ionization in the positive mode (ion trap, ESI<com:Sup>+< / com:Sup>). Within this Examples section, for sake of simplicity, nucleotides or nucleosides mentioned in this Examples section refer to beta anomers, unless mentioned specifically as alpha anomers. Furthermore, and consistent hereto, oligomers or oligonucleotides mentioned within this Examples section comprise beta anomers, unless mentioned specifically as alpha anomers. Temperature of melting UV-melting experiments were recorded on a Varian Cary Bio 100 UV / vis spectrophotometer. Experiments were performed at 2 µM duplex concentration, 10 mM NaH<com:Sub>2< / com:Sub>PO<com:Sub>4< / com:Sub>, between 0 M and 150 mM NaCl (alpha anomer) or between 0.05 M and 1.00 M NaCl (beta anomer) and pH adjusted to 7.0. Samples were protected from evaporation by a covering layer of dimethylpolysiloxane. Absorbance was monitored at 260 nm. For every experiment, three cooling-heating cycles were performed with a temperature gradient of 0.5°C / min. The maxima of the curves first derivative were extracted with Varian WinUV software and Tm values were reported as the average of the six ramps. Circular dichroism spectroscopy CD-spectra were recorded on a Jasco J-715 spectropolarimeter equipped with a Jasco PFO-350S temperature controller. Sample conditions were the same as for UV-melting experiments. Spectra were recorded between 210 and 320 nm at a 50 nm / min rate and the temperature was measured directly from the sample. For each experiment, a blank containing the same salt concentrations as the sample were recorded. The reported spectra were obtained by taking a smoothed average of three scans and subtracting the corresponding blank spectrum. Characterizations of oligonucleotides [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] <com:Sup>a< / com:Sup> A,G,T,C denote natural 2'-deoxynucleosides; a, g, t, c corresponds to modified adenine, guanine, thymine and methylcytosine respectively, * denotes a phosphorothioate linkage, c stands for the modified 5-methyl cytosine nucleoside. EXAMPLE 1 Syntheses of the Inventive Compounds (General Overview) The bicyclic scaffolds 7 and 10 envisaged for subsequent nucleoside synthesis could be constructed from the previously described intermediate 1 (Tarköy, M.; Bolli, M.; Schweizer, B.; Leumann, C. Helv. Chim. Acta 1993, 76, 481) (Scheme 1). The epoxide ring in 1 was efficiently opened by LiHMDS mediated intramolecular elimination at -78 °C, yielding the unsaturated ester 2 in good yield. Subsequent nickel-catalyzed NaBH<com:Sub>4< / com:Sub> reduction of 2 proceeded stereospecifically from the convex side of the bicyclic core structure, resulting in ester 3 as the only identifiable diastereoisomer. The hydroxyl function in 3 was then TBDPS protected, giving 4 in quantitative yield. Intermediate 4 was consequently reduced with DIBAL at -78°C, leading to aldehyde 5. The acetonide protecting group in 5 was then hydrolyzed under mild conditions with In(OTf)<com:Sub>3< / com:Sub> as catalyst (Golden, K. C.; Gregg, B. T.; Quinn, J. F. Tetrahedron Lett. 2010, 51, 4010), in a mixture of MeCN and H<com:Sub>2< / com:Sub>O, and the resulting bicyclic hemiacetal converted into the methyl glycoside 6 by simply changing the solvent to MeOH. Compound 6 was then acetylated to afford the protected precursor 7 that was used for the synthesis of the corresponding purine nucleosides via Vorbrüggen chemistry. [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] Scheme 1: (a) LiHMDS, THF, -78°C, 2h, 74%; (b) NaBH<com:Sub>4< / com:Sub>, NiCl<com:Sub>2< / com:Sub>, EtOH, <com:Math><semantics>0∘<annotation encoding="application / x-tex">0^{\circ}< / annotation>< / semantics>< / com:Math>C <com:Math><semantics>→<annotation encoding="application / x-tex">\rightarrow< / annotation>< / semantics>< / com:Math> rt, 2h, 90%; (c) TBDPSCl, I<com:Sub>2< / com:Sub>, N-methylimidazole, THF, rt, 3h, quant; (d) DiBAL-H, CH<com:Sub>2< / com:Sub>Cl<com:Sub>2< / com:Sub>, -78°C, 90 min, 89%; (e) i) In(OTf)<com:Sub>3< / com:Sub>, MeCN / H<com:Sub>2< / com:Sub>O, rt, 48 h, ii) MeOH, 6h, 81%; (f) Ac<com:Sub>2< / com:Sub>O, DMAP, DCM, rt, 2h, 96%; (g) i) TMSOTf, 2,6-lutidine, DCM, rt, 60 min, ii) TBAF, THF, 0°C, 20 min, 92 %; (h) DMTr-Cl, AgOTf, DCM / lutidine, rt, 4h, 93%; (i) TBAF, THF, rt, 20h, quant. The synthesis of the preferred pyrimidine nucleosides of the present invention consisted in the well-established application of the β-stereoselective NIH induced addition of the nucleobases to a corresponding bicyclic glycal (Medvecky, M.; Istrate, A.; Leumann, C. J. J. Org. Chem. 2015, 80, 3556; Dugovic, B.; Leumann, C. J. Journal of Organic Chemistry 2014, 79, 1271; Lietard, J.; Leumann, C. J. J. Org. Chem. 2012, 77, 4566). First, to introduce the thymine nucleobase, the N-iodosuccinimide (NIS) induced nucleosidation was performed on the direct precursor of glycal 8, where <com:Math><semantics>R1=TMS<annotation encoding="application / x-tex">R_1 = TMS< / annotation>< / semantics>< / com:Math>, that was easily obtained from 6 by treatment with TMSOTf only. This approach resulted in the stereoselective formation of the corresponding <com:Math><semantics>β<annotation encoding="application / x-tex">\beta< / annotation>< / semantics>< / com:Math>-nucleoside, however, with a significant contamination of 7% of the <com:Math><semantics>α<annotation encoding="application / x-tex">\alpha< / annotation>< / semantics>< / com:Math>- anomer that remained inseparable by standard chromatography techniques. It was reasoned that the <com:Math><semantics>β<annotation encoding="application / x-tex">\beta< / annotation>< / semantics>< / com:Math>-selectivity could be enhanced by increasing steric bulk at <com:Math><semantics>R1<annotation encoding="application / x-tex">R_1< / annotation>< / semantics>< / com:Math> and decreasing it at <com:Math><semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics>< / com:Math>, as in glycal 10. This would favor initial <com:Math><semantics>α<annotation encoding="application / x-tex">\alpha< / annotation>< / semantics>< / com:Math>-attack of the electrophilic iodine at C(4). To this end compound 6 was converted to glycal 8 with TMSOTf followed by a short treatment with TBAF to remove the newly introduced TMS group selectively. Intermediate 8 was then elaborated into the dimethoxytrityl compound 9 which was finally subjected to removal of the TBDPS protecting group with TBAF to give the desired sugar component 10. NIS-nucleosidation on the in situ TMS protected glycal 10, followed by radical reduction of the iodide intermediate with Bu<com:Sub>3< / com:Sub>SnH, yielded the DMTr-protected thymidine derivative 11 in good yield containing only trace amounts (<com:Math><semantics><2%<annotation encoding="application / x-tex"><2\%< / annotation>< / semantics>< / com:Math> by <com:Sup>1< / com:Sup>H-NMR) of the <com:Math><semantics>α<annotation encoding="application / x-tex">\alpha< / annotation>< / semantics>< / com:Math>-anomer (Scheme 2). Final phosphitylation with 2-cyanoethyl N,N,N',N'- tetraisopropylphosphordiamidite lead to the thymidine phosphoramidite building block 12. The synthesis of the 5-methylcytosine nucleoside was achieved by conversion of the base thymine. To this end, nucleoside 11 was TMS protected and converted to the corresponding triazolide by treatment with 1,2,4-triazole and POCl<com:Sub>3< / com:Sub>. Subsequent treatment of this triazolide in a mixture of ammonia and 1,4-dioxane yielded the corresponding 5-methylcytosine nucleoside, which was directly protected with Bz<com:Sub>2< / com:Sub>O to give 13 in 88% yield over three steps. The phosphoramidite 14 was obtained by a phosphitylation as described above. [Image disponible dans le document PDF, Image available in the PDF document] Scheme 2: (a) i) Thymine, BSA, NIS, DCM, rt, 7h; ii) Bu<com:Sub>3< / com:Sub>SnH, AIBN, toluene, 70°C, 30 min, 73%; (b) 2-Cyanoethyl N,N,N',N'-tetraisopropylphosphordiamidite, ETT, DCM, rt, 30 min, 70% for 12, 75% for 14; (c) i) BSA, Triazole, POCl<com:Sub>3< / com:Sub>, Et<com:Sub>3< / com:Sub>N, CH<com:Sub>3< / com:Sub>CN, rt, 5h, ii) 1,4- Dioxane / NH<com:Sub>4< / com:Sub>OH, rt, 2h, iii) Bz<com:Sub>2< / com:Sub>O, Et<com:Sub>3< / com:Sub>N, DMF, rt, 20h, 88%. Classical Vorbrüggen nucleosidation was applied for introducing the purine nucleobases resulted generally in the prevalence of the <com:Math><semantics>α<annotation encoding="application / x-tex">\alpha< / annotation>< / semantics>< / com:Math>-nucleosides. The conversion of precursor 7 with either N<com:Sup>6< / com:Sup>-benzoyladenine or 2-amino-6-chloropurine leads to the inseparable anomeric mixtures 15 and 20, resp. in <com:Math><semantics>α / β<annotation encoding="application / x-tex">\alpha / \beta< / annotation>< / semantics>< / com:Math> ratios of 4:1 and 7:3 (Scheme 3). Separation of anomers was possible after deacetylation, leading to the pure <com:Math><semantics>β<annotation encoding="application / x-tex">\beta< / annotation>< / semantics>< / com:Math>-anomers 16 and 21. From here, the adenine building block 19 could be obtained by standard dimethoxytritylation (<com:Math><semantics>→<annotation encoding="application / x-tex">\rightarrow< / annotation>< / semantics>< / com:Math> 17) followed TBAF mediated cleavage of the silyl protecting group (<com:Math><semantics>→<annotation encoding="application / x-tex">\rightarrow< / annotation>< / semantics>< / com:Math> 19) and phosphitylation. The synthesis of the guanine building block required the conversion of the 2-amino-6-chloropurine nucleobase. This was achieved by treatment of 21 with 3-hydroxypropionitrile and TBD and subsequent protection of the 2-amino group with DMF, yielding the protected guanosine derivatives 22. Following the same chemical pathway as above, the synthesis of the guanine building block 25 was achieved by dimethoxytritylation (<com:Math><semantics>→<annotation encoding="application / x-tex">\rightarrow< / annotation>< / semantics>< / com:Math> 23) followed by removal of silyl protecting group (<com:Math><semantics>→<annotation encoding="application / x-tex">\rightarrow< / annotation>< / semantics>< / com:Math> 24) and phosphitylation. [Image disponible dans le document PDF, Image available in the PDF document] Scheme 3: (a) N<com:Sup>6< / com:Sup>-Benzoyladenine, BSA, TMSOTf, MeCN, 70°C, 20 min, 64%; (b) NaOH, THF / MeOH / H<com:Sub>2< / com:Sub>O, 0°C, 20 min, 69%; (c) DMTr-Cl, pyridine, rt, 24h, 87%; (d) TBAF, THF, rt, 48h, 87%; (e) CEP-Cl, DIPEA, THF, rt, 2h, 71%; (f) 2-amino-6-chloropurine, BSA, TMSOTf, MeCN, 55°C, 50 min, 77%; (g) NaOH, THF / MeOH / H<com:Sub>2< / com:Sub>O, 0°C, 20 min, 85%; (i) i) TBD, 3-hydroxypropionitrile, DCM, 48h, ii) N,N-dimethylformamide dimethylacetal, DMF, 55°C, 2h, 73%; (j) DMTr-Cl, pyridine, rt, 18h, 70%; (k) TBAF, THF, rt, 7h, 87%; (l) 2- Cyanoethyl N,N,N',N'-tetraisopropylphosphordiamidite, ETT, DCM, rt, 50 min, 69%. Starting from protected sugar 7 the synthesis of four preferred phosphoramidite building blocks of the present invention was developed. Treatment of a mixture of sugar 7 and in situ silylated thymine with TMSOTf resulted in the smooth formation of the nucleoside 35, with a favorable anomeric ratio <com:Math><semantics>α / β<annotation encoding="application / x-tex">\alpha / \beta< / annotation>< / semantics>< / com:Math> of approximately 85:15 (determined by <com:Sup>1< / com:Sup>H-NMR) (Scheme 4). The chemical pathway leading to the thymidine phosphoramidite bearing the DMTr group on the 5' position does not allow the separation of anomers by standard chromatography. Therefore, and in order to introduce the modification with polarity reversal into DNA strands, the DMTr group was introduced on the 7' position. To this end, the silyl group of 35 was removed by short treatment with TBAF (<com:Math><semantics>→<annotation encoding="application / x-tex">\rightarrow< / annotation>< / semantics>< / com:Math> 36) followed by standard dimethoxytritylation (<com:Math><semantics>→<annotation encoding="application / x-tex">\rightarrow< / annotation>< / semantics>< / com:Math> 37). Separation of the two anomers was possible after standard deacetylation, leading to the pure <com:Math><semantics>α<annotation encoding="application / x-tex">\alpha< / annotation>< / semantics>< / com:Math>-anomer 38. The thymidine building block 39 was finally obtained by phosphitylation with 2-cyanoethyl N,N,N',N'-tetraisopropylphosphordiamidite in the presence of 5- (Ethylthio)-1H-tetrazole. The intermediate 38 also offered us short access to the 5- methylcytosine nucleoside, by conversion of the in situ TMS protected nucleoside 38 to the corresponding triazolide with POCl<com:Sub>3< / com:Sub> and 1,2,4-triazole, followed by treatment in a mixture of ammonia and 1,4-dioxane. Direct protection with Bz<com:Sub>2< / com:Sub>O in DMF resulted in the efficient formation of nucleoside 40, the labile silyl protecting group being cleaved during the process. Final phosphitylation in conditions as described above afforded the 5-methylcytidine phosphoramidite 41. [Image disponible dans le document PDF, Image available in the PDF document] Scheme 4: (a) Thymine, BSA, TMSOTf, MeCN, rt, 18h, 82%; (b) TBAF, THF, 2h, 75%; (c) DMTr-Cl, pyridine, rt, 24h, 96%; (d) K<com:Sub>2< / com:Sub>CO<com:Sub>3< / com:Sub>, MeOH, 3h, 86%; (e) 2-Cyanoethyl N,N,N',N'-tetraisopropylphosphordiamidite, ETT, DCM, rt, 1h, 81% for 39, 30 min, 80% for 41; f) i) BSA, 1,2,4-triazole, POCl<com:Sub>3< / com:Sub>, Et<com:Sub>3< / com:Sub>N, MeCN, rt, 7h, ii) 1,4-Dioxane / NH<com:Sub>4< / com:Sub>OH, rt, 3h, iii) Bz<com:Sub>2< / com:Sub>O, Et<com:Sub>3< / com:Sub>N, DMF, rt, 18h, 83%. For the purine nucleobases, the introduction of the purines were performed by a short nucleosidation in slightly elevated temperature with either N<com:Sup>6< / com:Sup>-benzoyladenine or 2-amino-6- chloropurine, leading to the nucleoside 15 and 20, resp. in <com:Math><semantics>α / β<annotation encoding="application / x-tex">\alpha / \beta< / annotation>< / semantics>< / com:Math> ratios of 4:1 and 7:3 (Scheme 5). To separate the anomers, acetyl groups were removed under mild conditions, yielding the pure <com:Math><semantics>α<annotation encoding="application / x-tex">\alpha< / annotation>< / semantics>< / com:Math>-anomers 42 and 48. The formation of the adenosine building block continues with the reintroduction of the acetyl protecting group (<com:Math><semantics>→<annotation encoding="application / x-tex">\rightarrow< / annotation>< / semantics>< / com:Math> 43), removal of the TPDPS protecting group with TBAF (<com:Math><semantics>→<annotation encoding="application / x-tex">\rightarrow< / annotation>< / semantics>< / com:Math> 44) followed by standard dimethoxytritylation (<com:Math><semantics>→<annotation encoding="application / x-tex">\rightarrow< / annotation>< / semantics>< / com:Math> 45). Selective deprotection of the acetyl group <com:Math><semantics>(→46)<annotation encoding="application / x-tex">(\rightarrow 46)< / annotation>< / semantics>< / com:Math> followed by phosphitylation in conditions as described above yielded the adenine building block 47. For the guanine building block, after separation of the two anomers, the 6-chloropurine was converted to the guanine nucleobase by treatment with TBD and 3-hydroxypropionitrile yielding the guanosine nucleoside 49. Acetylation over 48h allowed the concomitant protection of the 5'-hydroxy and 2-amino groups, yielding the protected nucleoside 50. Similarly as above, the DMTr group was introduced by removal of the silyl protecting group with TBAF (<com:Math><semantics>→<annotation encoding="application / x-tex">\rightarrow< / annotation>< / semantics>< / com:Math> 51) followed by dimethoxytritylation (<com:Math><semantics>→<annotation encoding="application / x-tex">\rightarrow< / annotation>< / semantics>< / com:Math> 52). The two acetyl groups were removed by treatment with K<com:Sub>2< / com:Sub>CO<com:Sub>3< / com:Sub> and the resulting polar product was directly protected with DMF to afford the guanosine nucleoside 53. Final phosphitylation yielded building block 54. [Image disponible dans le document PDF, Image available in the PDF document] Scheme 5: a) N<com:Sup>6< / com:Sup>-Benzoyladenine, BSA, TMSOTf, MeCN, 70°C, 20 min, 64%; (b) NaOH, THF / MeOH / H<com:Sub>2< / com:Sub>O, 0°C, 20 min, 51% α-anomer, 18% β-anomer; (c) Ac<com:Sub>2< / com:Sub>O, DMAP, DCM, rt, 18h, 90%; (d) TBAF, THF, rt, 3.5h, 90%; (e) DMTr-Cl, pyridine, rt, 24h, 89%; (f) NaOH, THF / MeOH / H<com:Sub>2< / com:Sub>O, 0°C, 30 min, 94% (g) 2-Cyanoethyl N,N,N',N'-tetraisopropyl- phosphordiamidite, ETT, DCM, rt, 1h, 77% for 47, 50 min, 67% for 54; (h) 2-amino-6- chloropurine, BSA, TMSOTf, MeCN, 55°C, 50 min, 77%; (i) NaOH, THF / MeOH / H<com:Sub>2< / com:Sub>O, 0°C, 20 min, 85%; (j) TBD, 3-hydroxypropionitrile, DCM, 48h, 87% (k) Ac<com:Sub>2< / com:Sub>O, DMAP, DCM, rt, 48h, 76%; (1) TBAF, THF, rt, 4h, 87%; (m) DMTr-Cl, pyridine, rt, 48h, 99%; (n) i) K<com:Sub>2< / com:Sub>CO<com:Sub>3< / com:Sub>, MeOH, rt, 7h, ii) N,N-dimethylformamide dimethylacetal, DMF, 55°C, 2h, 77%. EXAMPLE 2 Ethyl (E and Z, 1'R,5'S,7'R)-(7'-hydroxy-3',3'-dimethyl-2',4'-dioxabicyclo[3.3.0]oct-6'- ylidene)acetate (2a / b) [Image disponible dans le document PDF, Image available in the PDF document] A solution of the epoxide 1 (4.46 g, 18.4 mmol) in dry THF (100 mL) was cooled down to -78°C. Then LiHMDS (1M in THF, 22.1 mL, 22.1 mmol) was slowly added. The solution was stirred for 2 hours at -78°C before being allowed to warm to rt and neutralized with addition of 1M aqueous HCl (22.1 mL). The mixture was then diluted with EtOAc (100 mL) and THF was removed under reduced pressure. The mixture is then washed with 0.5 M NaH<com:Sub>2< / com:Sub>PO<com:Sub>4< / com:Sub> (50 mL) and aqueous phase extracted with EtOAc (2 X 50 mL). The combined organic phases were dried over MgSO<com:Sub>4< / com:Sub>, filtered and evaporated. The crude product was purified by CC (EtOAc / hexane 3:1) to yield the two isomers 2a / b (3.30 g, 74%) as a slightly yellow solid. Data for 2a: <com:Math><semantics>Rf=0.37<annotation encoding="application / x-tex">R_f = 0.37< / annotation>< / semantics>< / com:Math> (EtoAc / hexane 1:1); <com:Sup>1< / com:Sup>H NMR (300 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 6.07 – 5.98 (m, 1H, H-C(2)), 5.59 (d, <com:Math><semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>< / com:Math> = 6.0 Hz, 1H, H- <com:Math><semantics>C(5′)<annotation encoding="application / x-tex">C(5')< / annotation>< / semantics>< / com:Math>, 4.94 – 4.81 (m, 1H, H-<com:Math><semantics>C(1′)<annotation encoding="application / x-tex">C(1')< / annotation>< / semantics>< / com:Math>), 4.65 (t, <com:Math><semantics>J=5.6<annotation encoding="application / x-tex">J = 5.6< / annotation>< / semantics>< / com:Math> Hz, 1H, H-<com:Math><semantics>C(7′)<annotation encoding="application / x-tex">C(7')< / annotation>< / semantics>< / com:Math>), 4.18 (q, <com:Math><semantics>J=7.1<annotation encoding="application / x-tex">J = 7.1< / annotation>< / semantics>< / com:Math> Hz, 2H, CH<com:Sub>3< / com:Sub>CH<com:Sub>2< / com:Sub>), 2.67 (br, 1H, OH), 2.37 (dd, <com:Math><semantics>J=13.5<annotation encoding="application / x-tex">J = 13.5< / annotation>< / semantics>< / com:Math>, 7.5 Hz, 1H, H-C(8')), 1.55 – 1.42 (m, 1H, H-C(8')), 1.40, 1.33 (2s, 6H, <com:Math><semantics>(CH3)2C<annotation encoding="application / x-tex">(CH_3)_2C< / annotation>< / semantics>< / com:Math>), 1.26 (t, <com:Math><semantics>J=7.1<annotation encoding="application / x-tex">J = 7.1< / annotation>< / semantics>< / com:Math> Hz, 3H, <com:Math><semantics>CH2CH3<annotation encoding="application / x-tex">CH_2CH_3< / annotation>< / semantics>< / com:Math>). <com:Sup>13< / com:Sup>C NMR (75 MHz, CDCl<com:Sub>3< / com:Sub>) δ 165.75 (C(1)), 161.61 (C(6')), 116.53 (C(2)), 110.69 <com:Math><semantics>(C(3′))<annotation encoding="application / x-tex">(C(3'))< / annotation>< / semantics>< / com:Math>, 76.55 <com:Math><semantics>(C(5′))<annotation encoding="application / x-tex">(C(5'))< / annotation>< / semantics>< / com:Math>, 75.52 <com:Math><semantics>(C(1′))<annotation encoding="application / x-tex">(C(1'))< / annotation>< / semantics>< / com:Math>, 71.63 <com:Math><semantics>(C(7′))<annotation encoding="application / x-tex">(C(7'))< / annotation>< / semantics>< / com:Math>, 60.51 <com:Math><semantics>(CH2CH3)<annotation encoding="application / x-tex">(CH_2CH_3)< / annotation>< / semantics>< / com:Math>, 37.46 <com:Math><semantics>(C(8′))<annotation encoding="application / x-tex">(C(8'))< / annotation>< / semantics>< / com:Math>, 26.44, 24.11 ((CH<com:Sub>3< / com:Sub>)<com:Sub>2< / com:Sub>C), 14.27 (CH<com:Sub>2< / com:Sub>CH<com:Sub>3< / com:Sub>). <com:Math><semantics>ESI+<annotation encoding="application / x-tex">ESI^{+}< / annotation>< / semantics>< / com:Math>-HRMS <com:Math><semantics>m / z<annotation encoding="application / x-tex">m / z< / annotation>< / semantics>< / com:Math> calcd for <com:Math><semantics>C12H19O5<annotation encoding="application / x-tex">C_{12}H_{19}O_{5}< / annotation>< / semantics>< / com:Math> ([M + H]<com:Sup>+< / com:Sup>) 243.1227, found 243.1231. Data for 2b: <com:Math><semantics>Rf=0.52<annotation encoding="application / x-tex">R_f = 0.52< / annotation>< / semantics>< / com:Math> (EtoAc / hexane 1:1); <com:Sup>1< / com:Sup>H NMR (300 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 6.15 – 6.05 (m, 1H, H-C(2)), 5.37 – 5.02 (m, 2H, H- <com:Math><semantics>C(5′)<annotation encoding="application / x-tex">C(5')< / annotation>< / semantics>< / com:Math>, OH), 4.87 (d, <com:Math><semantics>J=3.4<annotation encoding="application / x-tex">J = 3.4< / annotation>< / semantics>< / com:Math> Hz, 1H, H-C(1')), 4.67 (t, <com:Math><semantics>J=4.9<annotation encoding="application / x-tex">J = 4.9< / annotation>< / semantics>< / com:Math> Hz, 1H, H-C(7')), 4.20 (qd, <com:Math><semantics>J=<annotation encoding="application / x-tex">J =< / annotation>< / semantics>< / com:Math> 7.1, 0.9 Hz, 2H, <com:Math><semantics>CH3CH2<annotation encoding="application / x-tex">CH_3CH_2< / annotation>< / semantics>< / com:Math>), 2.55 (dd, <com:Math><semantics>J=14.6<annotation encoding="application / x-tex">J = 14.6< / annotation>< / semantics>< / com:Math>, 8.1 Hz, 1H, <com:Math><semantics>H−C(8′)<annotation encoding="application / x-tex">H-C(8')< / annotation>< / semantics>< / com:Math>), 1.94 – 1.77 (m, 1H, <com:Math><semantics>H−C(8′)<annotation encoding="application / x-tex">H-C(8')< / annotation>< / semantics>< / com:Math>) <com:Math><semantics>C(8′)<annotation encoding="application / x-tex">C(8')< / annotation>< / semantics>< / com:Math>, 1.39 – 1.25 (m, 9H, <com:Math><semantics>(CH3)2<annotation encoding="application / x-tex">(CH_3)_2< / annotation>< / semantics>< / com:Math>C, <com:Math><semantics>CH2<annotation encoding="application / x-tex">CH_2< / annotation>< / semantics>< / com:Math>C<com:Math><semantics>H3<annotation encoding="application / x-tex">H_3< / annotation>< / semantics>< / com:Math>). <com:Sup>13< / com:Sup>C NMR (75 MHz, CDCl<com:Sub>3< / com:Sub>) δ 167.91 (C(1)), 167.43 (C(6')), 120.13 (C(2)), 111.75 <com:Math><semantics>(C(3′))<annotation encoding="application / x-tex">(C(3'))< / annotation>< / semantics>< / com:Math>, 81.62 <com:Math><semantics>(C(5′))<annotation encoding="application / x-tex">(C(5'))< / annotation>< / semantics>< / com:Math>, 78.08 <com:Math><semantics>(C(1′))<annotation encoding="application / x-tex">(C(1'))< / annotation>< / semantics>< / com:Math>, 70.85 <com:Math><semantics>(C(7′))<annotation encoding="application / x-tex">(C(7'))< / annotation>< / semantics>< / com:Math>, 61.25 <com:Math><semantics>(CH2CH3)<annotation encoding="application / x-tex">(CH_2CH_3)< / annotation>< / semantics>< / com:Math>, 36.53 <com:Math><semantics>(C(8′))<annotation encoding="application / x-tex">(C(8'))< / annotation>< / semantics>< / com:Math>, 27.38, <com:Math><semantics>25.45((CH3)2C),14.19(CH2CH3).<annotation encoding="application / x-tex">25.45 ((CH_3)_2C), 14.19 (CH_2CH_3).< / annotation>< / semantics>< / com:Math> <com:Math><semantics>ESI+<annotation encoding="application / x-tex">ESI^{+}< / annotation>< / semantics>< / com:Math>-HRMS <com:Math><semantics>m / z<annotation encoding="application / x-tex">m / z< / annotation>< / semantics>< / com:Math> calcd for <com:Math><semantics>C12H19O5<annotation encoding="application / x-tex">C_{12}H_{19}O_{5}< / annotation>< / semantics>< / com:Math> ([M + H]<com:Sup>+< / com:Sup>) 243.1227, found 243.1227. EXAMPLE 3 Ethyl (1'R,5'S,6'S,7'R)-(7'-hydroxy-3',3'-dimethyl-2',4'-dioxabicyclo[3.3.0]oct-6'- yl)acetate (3) [Image disponible dans le document PDF, Image available in the PDF document] To a solution of the alcohols 2a / b (12.65 g, 52.2 mmol) and nickel chloride hexahydrate (2.48 g, 10.4 mmol) in EtOH (300 mL) was added portion wise sodium borohydride (9.88 g, 261 mmol) at 0°C. The resulting dark solution was stirred for 30 min at 0°C and 90 min at rt. Then EtOH was carefully concentrated under reduced pressure, the resulting solid diluted with EtOAc (200 mL) and the excess of NaBH<com:Sub>4< / com:Sub> quenched by addition of water (100 mL) at 0°C followed by stirring at rt for 30 min. The two phases are then separated. Organic phase was washed with water (100 mL). Aqueous phases are then combined, filtered and extracted with EtOAc (2 X 100 mL). The combined organic phases were dried over MgSO<com:Sub>4< / com:Sub>, filtered and concentrated. The crude product was purified by CC (EtOAc / hexane 2:1) to yield 3 (11.4) g, 90%) as a white solid. Data for 3: <com:Math><semantics>Rf=0.40<annotation encoding="application / x-tex">R_f = 0.40< / annotation>< / semantics>< / com:Math> (EtOAc / hexane 1:1); <com:Sup>1< / com:Sup>H NMR (300 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 4.65 – 4.52 (m, 2H, H-C(1'), H-C(5')), 4.15 (qd, <com:Math><semantics>J<annotation encoding="application / x-tex">J< / annotation>< / semantics>< / com:Math> = 7.1, 1.4 Hz, 2H, <com:Math><semantics>CH3CH2<annotation encoding="application / x-tex">CH_3CH_2< / annotation>< / semantics>< / com:Math>), 4.05 (ddd, <com:Math><semantics>J=10.0<annotation encoding="application / x-tex">J = 10.0< / annotation>< / semantics>< / com:Math>, 9.99, 6.2 Hz, 1H, <com:Math><semantics>H−C(7′)<annotation encoding="application / x-tex">H-C(7')< / annotation>< / semantics>< / com:Math>), 2.86 (<com:Math><semantics>br<annotation encoding="application / x-tex">br< / annotation>< / semantics>< / com:Math>, s, 1H, <com:Math><semantics>OH<annotation encoding="application / x-tex">OH< / annotation>< / semantics>< / com:Math>), <com:Math><semantics>2.65 (qd, J=16.9,7.1 Hz, 2H,H−C(2)),2.24 (dd, J=13.7,6.2 Hz, 1H,H−C(8′)),1.93 (dt, J=16.9,7.1 Hz, 2H,H−C(2)),2.24 (dd, J=13.7,6.2 Hz, 1H,H−C(8′)),1.93 (dt, <annotation encoding="application / x-tex">2.65 \text{ (qd, } J = 16.9, 7.1 \text{ Hz, } 2H, H-C(2)), 2.24 \text{ (dd, } J = 13.7, 6.2 \text{ Hz, } 1H, H-C(8')), 1.93 \text{ (dt, } J = 16.9, 7.1 \text{ Hz, } 2H, H-C(2)), 2.24 \text{ (dd, } J = 13.7, 6.2 \text{ Hz, } 1H, H-C(8')), 1.93 \text{ (dt, }< / annotation>< / semantics>< / com:Math> = 12.7, 7.1 Hz, 1H. H-C(6')), 1.56 (ddd, <com:Math><semantics>J=13.9<annotation encoding="application / x-tex">J = 13.9< / annotation>< / semantics>< / com:Math>, 10.2, 5.5 Hz, 1H, H-C(8')), 1.38 (s, 3H, <com:Math><semantics>(CH3)2C<annotation encoding="application / x-tex">(CH_3)_2C< / annotation>< / semantics>< / com:Math>, 1.30 - 1.21 (m, 6H, <com:Math><semantics>(CH3)2C<annotation encoding="application / x-tex">(CH_3)_2C< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>CH2CH3<annotation encoding="application / x-tex">CH_2CH_3< / annotation>< / semantics>< / com:Math>). <com:Sup>13< / com:Sup>C NMR (75 MHz, CDCl<com:Sub>3< / com:Sub>) δ 174.38 (C(1)), 109.06 (C(3')), 79.65 (C(5')), 77.19 <com:Math><semantics>(C(1′),74.32(C(7′),60.80(CH2CH3),46.66(C(6′)),40.38(C(8′)),32.43(C(2)),26.00,23.69)<annotation encoding="application / x-tex">(C(1'), 74.32 (C(7'), 60.80 (CH2CH3), 46.66 (C(6')), 40.38 (C(8')), 32.43 (C(2)), 26.00, 23.69)< / annotation>< / semantics>< / com:Math> <com:Math><semantics>((CH3)2C)<annotation encoding="application / x-tex">((CH_3)_2C)< / annotation>< / semantics>< / com:Math>, 14.17 <com:Math><semantics>(CH2CH3)<annotation encoding="application / x-tex">(CH_2CH_3)< / annotation>< / semantics>< / com:Math>. <com:Math><semantics>ESI+<annotation encoding="application / x-tex">ESI^{+}< / annotation>< / semantics>< / com:Math>-HRMS <com:Math><semantics>m / z<annotation encoding="application / x-tex">m / z< / annotation>< / semantics>< / com:Math> calcd for <com:Math><semantics>C12H21O5<annotation encoding="application / x-tex">C_{12}H_{21}O_{5}< / annotation>< / semantics>< / com:Math> ([M + H]<com:Sup>+< / com:Sup>) 245.1384, found 245.1388. EXAMPLE 4 Ethyl (1'R,5'S,6'S,7'R)-(7'-(tert-butyldiphenylsilyl)oxy)-3',3'-dimethyl-2',4'- dioxabicyclo[3.3.0]oct-6'-yl)acetate (4) [Image disponible dans le document PDF, Image available in the PDF document] To a solution of the alcohol 3 (2.50 g, 10.2 mmol), N-methylimidazole (12.6 g, 153 mmol) and iodine (7.80 g, 30.6 mmol) in dry THF (60 mL) was added dropwise tert- butyl(chloro)diphenylsilane (3.0 mL, 11.2 mmol) at rt. The solution was stirred for 3 hours at rt and hen THF was evaporated, the mixture diluted with EtOAc (50 mL) and washed with 10% aqueous Na<com:Sub>2< / com:Sub>O<com:Sub>3< / com:Sub>S<com:Sub>2< / com:Sub> (2 X 40 mL). Aqueous phases are then combined and extracted with EtOAc (50 mL). The combined organic phases were dried over MgSO<com:Sub>4< / com:Sub>, filtered and evaporated. The crude product was purified by CC (EtOAc / hexane 1:10) to yield 4 (5.01 g, quantitative yield) as a white solid Data for 4: <com:Math><semantics>Rf=0.87<annotation encoding="application / x-tex">R_f = 0.87< / annotation>< / semantics>< / com:Math> (DCM / MeOH 10:1); <com:Sup>1< / com:Sup>H NMR (300 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.77 – 7.59 (m, 4H, H-arom), 7.51 – 7.32 (m, 6H, H- arom), 4.61 (t, <com:Math><semantics>J=5.7<annotation encoding="application / x-tex">J = 5.7< / annotation>< / semantics>< / com:Math> Hz, 1H, H-C(5')), 4.49 (t, <com:Math><semantics>J=5.7<annotation encoding="application / x-tex">J = 5.7< / annotation>< / semantics>< / com:Math> Hz, 1H, H-C(1')), 4.15 (q, <com:Math><semantics>J=6.9<annotation encoding="application / x-tex">J = 6.9< / annotation>< / semantics>< / com:Math> Hz, 2H, <com:Math><semantics>CH3CH2<annotation encoding="application / x-tex">CH_3CH_2< / annotation>< / semantics>< / com:Math>), 3.96 (dd, <com:Math><semantics>J=15.5<annotation encoding="application / x-tex">J = 15.5< / annotation>< / semantics>< / com:Math>, 9.5 Hz, 1H, <com:Math><semantics>H−C(7)<annotation encoding="application / x-tex">H-C(7)< / annotation>< / semantics>< / com:Math>), 2.64 – 2.32 (m, 2H, <com:Math><semantics>H−C(2)<annotation encoding="application / x-tex">H-C(2)< / annotation>< / semantics>< / com:Math>), 2.15 (tt, <Formule mathématique disponible dans le document PDF, Math available in the PDF document>J = 9.0, 4.3 \text{ Hz}, 1H, H-C(6'), 1.83 \text{ (dd}, J = 12.7, 5.2 Hz, 1H, H-C(8'))}, 1.61 - 1.45 \text{ (m, 1H, 1H, 1H, 1H, 1H, 1H, 1H, 1H, 1H, 1H H-C(8')), 1.27 (td, <com:Math><semantics>J=7.1<annotation encoding="application / x-tex">J = 7.1< / annotation>< / semantics>< / com:Math>, 1.9 Hz, 3H, CH<com:Sub>2< / com:Sub>CH<com:Sub>3< / com:Sub>), 1.18 (s, 6H, (CH<com:Sub>3< / com:Sub>)<com:Sub>2< / com:Sub>C), 1.09, 1.08 (2s, 9H, <com:Math><semantics>(CH3)3<annotation encoding="application / x-tex">(CH_3)_3< / annotation>< / semantics>< / com:Math>-C-Si) <com:Sup>13< / com:Sup>C NMR (75 MHz, CDCl<com:Sub>3< / com:Sub>) δ 173.07 (C(1)), 135.87, 135.85(CH-arom), 134.08, 133.73 (C-arom), 129.80, 129.75, 127.67, 127.58 (CH-arom), 108.82 (C(3')), 77.92 (C(5')), 76.96 <com:Math><semantics>(C(1′))<annotation encoding="application / x-tex">(C(1'))< / annotation>< / semantics>< / com:Math>, 74.93 <com:Math><semantics>(C(7′))<annotation encoding="application / x-tex">(C(7'))< / annotation>< / semantics>< / com:Math>, 60.24 <com:Math><semantics>(CH2CH3)<annotation encoding="application / x-tex">(CH_2CH_3)< / annotation>< / semantics>< / com:Math>, 47.27 <com:Math><semantics>(C(6′))<annotation encoding="application / x-tex">(C(6'))< / annotation>< / semantics>< / com:Math>, 40.27 <com:Math><semantics>(C(8′))<annotation encoding="application / x-tex">(C(8'))< / annotation>< / semantics>< / com:Math>, 31.10 <com:Math><semantics>(C(2))<annotation encoding="application / x-tex">(C(2))< / annotation>< / semantics>< / com:Math>, 27.04 <com:Math><semantics>(CH3)3<annotation encoding="application / x-tex">(CH_3)_3< / annotation>< / semantics>< / com:Math>-C-Si), 25.86 <com:Math><semantics>((CH3)2C)<annotation encoding="application / x-tex">((CH_3)_2C)< / annotation>< / semantics>< / com:Math>, 23.83 <com:Math><semantics>((CH3)2C)<annotation encoding="application / x-tex">((CH_3)_2C)< / annotation>< / semantics>< / com:Math>, 19.23 <com:Math><semantics>(CH3)3<annotation encoding="application / x-tex">(CH_3)_3< / annotation>< / semantics>< / com:Math>-C-Si), 14.24 <com:Math><semantics>(CH2<annotation encoding="application / x-tex">(CH_2< / annotation>< / semantics>< / com:Math>-CH<com:Sub>3< / com:Sub>). <com:Math><semantics>ESI+<annotation encoding="application / x-tex">ESI^{+}< / annotation>< / semantics>< / com:Math>-HRMS <com:Math><semantics>m / z<annotation encoding="application / x-tex">m / z< / annotation>< / semantics>< / com:Math> calcd for <com:Math><semantics>C28H39O5Si([M+H]+)<annotation encoding="application / x-tex">C_{28}H_{39}O_{5}Si([M + H]^{+})< / annotation>< / semantics>< / com:Math> 483.2561, found 483.2562. [Image disponible dans le document PDF, Image available in the PDF document] A solution of the ester 4 (8.56 g, 16.3 mmol) in dry DCM (120 mL) was cool down to - 78°C and then DiBAL-H (1M in cyclohexane, 18 mL, 18 mmol) was slowly added. The solution was further stirred at -78°C for 90 min before being allowed to warm to rt. Reaction was quenched by addition of 0.5 M aqueous NaH<com:Sub>2< / com:Sub>PO<com:Sub>4< / com:Sub> (100 mL). The organic phase was separated and aqueous phase was further extracted with DCM (2 X 100 mL). The combined organic phases were dried over MgSO<com:Sub>4< / com:Sub>, filtered and evaporated. The crude product was purified by CC (EtOAc / hexane 2:10 to 2:1) to yield aldehyde 5 (6.36 g, 89%) and alcohol 34 (0.637 g, 9%). Data for 5: <com:Math><semantics>Rf=0.65<annotation encoding="application / x-tex">R_f = 0.65< / annotation>< / semantics>< / com:Math> (EtOAc / hexane 2:1); <com:Sup>1< / com:Sup>H NMR (300 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 9.72 (s, 1H, H-C(1)), 7.65 (td, <com:Math><semantics>J=8.0<annotation encoding="application / x-tex">J = 8.0< / annotation>< / semantics>< / com:Math>, 1.6 Hz, 4H, H- arom), <com:Math><semantics>7.47−7.33<annotation encoding="application / x-tex">7.47 - 7.33< / annotation>< / semantics>< / com:Math> (m, 6H, H-arom), <com:Math><semantics>4.57<annotation encoding="application / x-tex">4.57< / annotation>< / semantics>< / com:Math> (t, <com:Math><semantics>J=5.7<annotation encoding="application / x-tex">J = 5.7< / annotation>< / semantics>< / com:Math> Hz, 1H, H-C(5')), <com:Math><semantics>4.51<annotation encoding="application / x-tex">4.51< / annotation>< / semantics>< / com:Math> (t, <com:Math><semantics>J=5.7<annotation encoding="application / x-tex">J = 5.7< / annotation>< / semantics>< / com:Math> Hz, 1H, H-C(1')), 3.99 (td, <com:Math><semantics>J=10.0<annotation encoding="application / x-tex">J = 10.0< / annotation>< / semantics>< / com:Math>, 5.9 Hz, 1H, H-C(7')), 2.58 – 2.43 (m, 2H, H-C(2)), 2.20 – 2.08 (m, 1H, H-C(6')), 1.87 (dd, <com:Math><semantics>J=13.5<annotation encoding="application / x-tex">J = 13.5< / annotation>< / semantics>< / com:Math>, 5.9 Hz, 1H, H-C(8')), 1.53 (ddd, <com:Math><semantics>J=13.5<annotation encoding="application / x-tex">J = 13.5< / annotation>< / semantics>< / com:Math>, 10.1, 5.5 Hz, 1H, H-C(8')), 1.16 (d, <com:Math><semantics>J=3.5<annotation encoding="application / x-tex">J = 3.5< / annotation>< / semantics>< / com:Math> Hz, 6H, ((C<com:Math><semantics>H3<annotation encoding="application / x-tex">H_3< / annotation>< / semantics>< / com:Math>)<com:Sub>2< / com:Sub>C), 1.05 (s, 9H, (C<com:Math><semantics>H3<annotation encoding="application / x-tex">H_3< / annotation>< / semantics>< / com:Math>)<com:Sub>3< / com:Sub>-C-Si). <com:Sup>13< / com:Sup>C NMR (75 MHz, CDCl<com:Sub>3< / com:Sub>) δ 201.87 (C(1)), 135.93, 135.90 (CH-arom), 133.96, 133.73 (C-arom), 129.96, 129.89, 127.79, 127.68 (CH-arom), 108.89 (C(3')), 77.76 (C(5')), 77.17 <com:Math><semantics>(C(1′))<annotation encoding="application / x-tex">(C(1'))< / annotation>< / semantics>< / com:Math>, 74.96 <com:Math><semantics>(C(7′))<annotation encoding="application / x-tex">(C(7'))< / annotation>< / semantics>< / com:Math>, 45.44 <com:Math><semantics>(C(6′))<annotation encoding="application / x-tex">(C(6'))< / annotation>< / semantics>< / com:Math>, 41.31 <com:Math><semantics>(C(2))<annotation encoding="application / x-tex">(C(2))< / annotation>< / semantics>< / com:Math>, 40.16 <com:Math><semantics>(C(8′))<annotation encoding="application / x-tex">(C(8'))< / annotation>< / semantics>< / com:Math>, 27.08 <com:Math><semantics>(CH3)3<annotation encoding="application / x-tex">(CH_3)_3< / annotation>< / semantics>< / com:Math>-C-Si), 25.87 <com:Math><semantics>((CH3)2C)<annotation encoding="application / x-tex">((CH_3)_2C)< / annotation>< / semantics>< / com:Math>, 23.79<com:Math><semantics>((CH3)2C)<annotation encoding="application / x-tex">((CH_3)_2C)< / annotation>< / semantics>< / com:Math>, 19.25 <com:Math><semantics>(CH3)3<annotation encoding="application / x-tex">(CH_3)_3< / annotation>< / semantics>< / com:Math>-C-Si). <com:Math><semantics>ESI+<annotation encoding="application / x-tex">ESI^{+}< / annotation>< / semantics>< / com:Math>-HRMS <com:Math><semantics>m / z<annotation encoding="application / x-tex">m / z< / annotation>< / semantics>< / com:Math> calcd for <com:Math><semantics>C26H35O4Si<annotation encoding="application / x-tex">C_{26}H_{35}O_{4}Si< / annotation>< / semantics>< / com:Math> ([M + H]<com:Sup>+< / com:Sup>) 439.2299, found 439.2297. EXAMPLE 6 (3aR,4R,6R,6aS)-4-((tert-butyldiphenylsilyl)oxy)-2-methoxyhexahydro-2H- cyclopenta[b]furan-6-ol (6) [Image disponible dans le document PDF, Image available in the PDF document] To a solution of the aldehyde 5 (13.73 g, 31.31 mmol) in MeCN (170 mL) and H<com:Sub>2< / com:Sub>O (19 mL) was added Indium(III) trifluoromethanesulfonate (703 mg, 1.25 mmol). The solution was further stirred for 48 hours, and then solvents were removed under reduced pressure and coevaporated with toluene. The residue was dissolved in dry MeOH and stirred for 6 hours. After evaporation of solvent, the crude product was purified by CC (EtOAc / hexane 3:10) to yield a mixture of 6 (10.50 g, 81%) in an anomeric ratio <com:Math><semantics>α / β≈4:1<annotation encoding="application / x-tex">\alpha / \beta \approx 4:1< / annotation>< / semantics>< / com:Math> as a colorless oil. Data for 6: <com:Math><semantics>Rf=0.53<annotation encoding="application / x-tex">R_f = 0.53< / annotation>< / semantics>< / com:Math> (EtOAc / hexane 1:1); <com:Sup>1< / com:Sup>H NMR (300 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.63 (dd, <com:Math><semantics>J=7.1<annotation encoding="application / x-tex">J = 7.1< / annotation>< / semantics>< / com:Math>, 0.6 Hz, 4H, H-arom), 7.46 – 7.34 (m, 6H, H-arom), 4.98 (d, <com:Math><semantics>J=4.8<annotation encoding="application / x-tex">J = 4.8< / annotation>< / semantics>< / com:Math> Hz, 0.8H, H-C(2)), 4.91 (dd, <com:Math><semantics>J=5.9<annotation encoding="application / x-tex">J = 5.9< / annotation>< / semantics>< / com:Math>, 1.3 Hz, 0.2 H, H-C(2)), <com:Math><semantics>4.63−4.54<annotation encoding="application / x-tex">4.63 - 4.54< / annotation>< / semantics>< / com:Math> (m, 1H, H-C(6a)), <com:Math><semantics>4.53−4.37<annotation encoding="application / x-tex">4.53 - 4.37< / annotation>< / semantics>< / com:Math> (m, 1H, H-C(6)), <com:Math><semantics>4.09<annotation encoding="application / x-tex">4.09< / annotation>< / semantics>< / com:Math> (m, <com:Math><semantics>0.2<annotation encoding="application / x-tex">0.2< / annotation>< / semantics>< / com:Math> H, H-C(4)), <com:Math><semantics>3.92<annotation encoding="application / x-tex">3.92< / annotation>< / semantics>< / com:Math> (br, <com:Math><semantics>0.8 H<annotation encoding="application / x-tex">0.8 \text{ H}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>H−C(4)<annotation encoding="application / x-tex">H-C(4)< / annotation>< / semantics>< / com:Math>), <com:Math><semantics>3.29<annotation encoding="application / x-tex">3.29< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>3.27<annotation encoding="application / x-tex">3.27< / annotation>< / semantics>< / com:Math> (2s, <com:Math><semantics>3 H<annotation encoding="application / x-tex">3 \text{ H}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>MeO<annotation encoding="application / x-tex">MeO< / annotation>< / semantics>< / com:Math>), <com:Math><semantics>2.79<annotation encoding="application / x-tex">2.79< / annotation>< / semantics>< / com:Math> (dd, <com:Math><semantics>J=17.0<annotation encoding="application / x-tex">J = 17.0< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>8.2 Hz<annotation encoding="application / x-tex">8.2 \text{ Hz}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>0.8H<annotation encoding="application / x-tex">0.8 \text{H}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>H−C(3a)<annotation encoding="application / x-tex">H-C(3a)< / annotation>< / semantics>< / com:Math>), <com:Math><semantics>2.64−17.0<annotation encoding="application / x-tex">2.64 - 17.0< / annotation>< / semantics>< / com:Math> 2.51 (m, 0.2 H, H-C(3a)), 2.29 (d, <com:Math><semantics>J=8.1<annotation encoding="application / x-tex">J = 8.1< / annotation>< / semantics>< / com:Math> Hz, 1H, OH), <com:Math><semantics>2.10−1.80<annotation encoding="application / x-tex">2.10 - 1.80< / annotation>< / semantics>< / com:Math> (m, 2.4 H, H-C(3), H- <com:Math><semantics>C(5)<annotation encoding="application / x-tex">C(5)< / annotation>< / semantics>< / com:Math>), 1.65 (ddd, <com:Math><semantics>J=13.2<annotation encoding="application / x-tex">J = 13.2< / annotation>< / semantics>< / com:Math>, 9.1, 4.4 Hz, 0.8 H, H-C(5)), 1.44 – 1.34 (m, 0.2 H, H-C(3)), 1.22 <com:Math><semantics>(ddd,J=13.2,8.1,4.9Hz,0.8H,H−C(3)),1.05(s,9H,(CH3)3−C−Si).<annotation encoding="application / x-tex">(ddd, J = 13.2, 8.1, 4.9 Hz, 0.8 H, H-C(3)), 1.05 (s, 9H, (CH3)3-C-Si).< / annotation>< / semantics>< / com:Math> <com:Sup>13< / com:Sup>C NMR (75 MHz, CDCl<com:Sub>3< / com:Sub>) δ 135.78, 135.74 (CH-arom), 133.96, 133.84 (C-arom), 129.78, 127.72 (CH-arom), 107.21, 106.50 (C(2)), 85.37, 81.76 (C(6a)), 78.11, 77.19 (C(4)), 73.03, 72.44 (C(6)), 55.30, 54.46 (MeO), 50.91, 49.67 (C(3a)), 41.13, 40.29 (C(3)), 38.16, <com:Math><semantics>37.98(C(5)),26.96,26.92(CH3)3−C−Si),19.07(CH3)3−C−Si).<annotation encoding="application / x-tex">37.98 (C(5)), 26.96, 26.92 (CH3)3-C-Si), 19.07 (CH3)3-C-Si).< / annotation>< / semantics>< / com:Math> <com:Math><semantics>ESI+<annotation encoding="application / x-tex">ESI^{+}< / annotation>< / semantics>< / com:Math>-HRMS <com:Math><semantics>m / z<annotation encoding="application / x-tex">m / z< / annotation>< / semantics>< / com:Math> calcd for <com:Math><semantics>C26H35O4Si([M+H]+)<annotation encoding="application / x-tex">C_{26}H_{35}O_{4}Si([M + H]^{+})< / annotation>< / semantics>< / com:Math> 435.1962, found 435.1950. EXAMPLE 7 (3aR,4R,6R,6aS)-4-((tert-butyldiphenylsilyl)oxy)-2-methoxyhexahydro-2H- cyclopenta[b]furan-6-yl acetate (7) [Image disponible dans le document PDF, Image available in the PDF document] To a solution of sugar 6 (3.35 g, 8.12 mmol) and 4-Dimethylaminopyridine (1.29 g, 10.6 mmol) in dry DCM (100 mL) was added acetic anhydride (3.8 mL, 41 mmol) at rt. After stirring for 2 h, reaction is quenched by slow addition of satd NaHCO<com:Sub>3< / com:Sub> (10 mL). The mixture is then diluted with satd NaHCO<com:Sub>3< / com:Sub> (50 mL) and extracted with DCM (3 X 50 mL). The combined organic phases were dried over MgSO<com:Sub>4< / com:Sub>, filtered and evaporated. The crude product was purified by CC (EtOAc / Hexanne 1:2) to yield a mixture of 7 (3.53 g, 96%) in an anomeric ratio <com:Math><semantics>α / β≈4:1<annotation encoding="application / x-tex">\alpha / \beta \approx 4:1< / annotation>< / semantics>< / com:Math> as a colorless oil. Data for 7: <com:Math><semantics>Rf=0.42<annotation encoding="application / x-tex">R_f = 0.42< / annotation>< / semantics>< / com:Math> (EtOAc / hexane 1:2); <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.70 – 7.59 (m, 4H, H-arom), 7.48 – 7.34 (m, 6H, H- arom), 5.41 (dt, <com:Math><semantics>J=11.0<annotation encoding="application / x-tex">J = 11.0< / annotation>< / semantics>< / com:Math>, 5.6 Hz, 0.8H, H-C(6)), 5.28 (ddd, <com:Math><semantics>J=11.7<annotation encoding="application / x-tex">J = 11.7< / annotation>< / semantics>< / com:Math>, 6.6, 5.2 Hz, 0.2H, H- <com:Math><semantics>C(6)<annotation encoding="application / x-tex">C(6)< / annotation>< / semantics>< / com:Math>), 4.99 (d, <com:Math><semantics>J=4.8<annotation encoding="application / x-tex">J = 4.8< / annotation>< / semantics>< / com:Math> Hz, 0.8H, H-<com:Math><semantics>C(2)<annotation encoding="application / x-tex">C(2)< / annotation>< / semantics>< / com:Math>), 4.89 – 4.81(m, 0.4H, H-<com:Math><semantics>C(2)<annotation encoding="application / x-tex">C(2)< / annotation>< / semantics>< / com:Math>), H-<com:Math><semantics>C(6a)<annotation encoding="application / x-tex">C(6a)< / annotation>< / semantics>< / com:Math>), 4.76 – 4.69 (m, 0.8H, H-C(6a)), 4.11 (d, <com:Math><semantics>J=5.1<annotation encoding="application / x-tex">J = 5.1< / annotation>< / semantics>< / com:Math> Hz, 0.2H, H-C(4)), 3.90 (d, <com:Math><semantics>J=4.0<annotation encoding="application / x-tex">J = 4.0< / annotation>< / semantics>< / com:Math> Hz, 0.8H, H-C(4)), 3.27, 3.24 (2s, 3H, MeO), 2.81 (dd, <com:Math><semantics>J=16.6<annotation encoding="application / x-tex">J = 16.6< / annotation>< / semantics>< / com:Math>, 7.6 Hz, 0.8H, H-C(3a)), 2.60 (dd, <com:Math><semantics>J=10.1<annotation encoding="application / x-tex">J = 10.1< / annotation>< / semantics>< / com:Math>, 7.0 Hz, 0.2H, H-C(3a)), <com:Math><semantics>2.30−2.18<annotation encoding="application / x-tex">2.30 - 2.18< / annotation>< / semantics>< / com:Math> (m, <com:Math><semantics>0.2<annotation encoding="application / x-tex">0.2< / annotation>< / semantics>< / com:Math> H, H-C(5)), <com:Math><semantics>2.12<annotation encoding="application / x-tex">2.12< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>2.10<annotation encoding="application / x-tex">2.10< / annotation>< / semantics>< / com:Math> (2s, <com:Math><semantics>J=4.7<annotation encoding="application / x-tex">J = 4.7< / annotation>< / semantics>< / com:Math> Hz, <com:Math><semantics>3<annotation encoding="application / x-tex">3< / annotation>< / semantics>< / com:Math>H, <com:Math><semantics>MeCO2<annotation encoding="application / x-tex">MeCO_2< / annotation>< / semantics>< / com:Math>), <com:Math><semantics>2.07−1.82<annotation encoding="application / x-tex">2.07 - 1.82< / annotation>< / semantics>< / com:Math> (m, <com:Math><semantics>2.8H<annotation encoding="application / x-tex">2.8H< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>H−C(5)<annotation encoding="application / x-tex">H-C(5)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>H−C(3)<annotation encoding="application / x-tex">H-C(3)< / annotation>< / semantics>< / com:Math>), <com:Math><semantics>1.24<annotation encoding="application / x-tex">1.24< / annotation>< / semantics>< / com:Math> (ddd, <com:Math><semantics>J=12.9<annotation encoding="application / x-tex">J = 12.9< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>7.6<annotation encoding="application / x-tex">7.6< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>3.7<annotation encoding="application / x-tex">3.7< / annotation>< / semantics>< / com:Math> Hz, <com:Math><semantics>1H<annotation encoding="application / x-tex">1H< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>H−C(3)<annotation encoding="application / x-tex">H-C(3)< / annotation>< / semantics>< / com:Math>), <com:Math><semantics>1.07<annotation encoding="application / x-tex">1.07< / annotation>< / semantics>< / com:Math> (s, 9H, <com:Math><semantics>(CH3)3<annotation encoding="application / x-tex">(CH_3)_3< / annotation>< / semantics>< / com:Math>-C-Si). <com:Sup>13< / com:Sup>C NMR (75 MHz, CDCl<com:Sub>3< / com:Sub>) δ 170.75, 170.66 (MeCO<com:Sub>2< / com:Sub>), 135.77, 135.73, 135.72 (CH- arom), 133.75, 133.65 (C-arom), 129.82, 129.74, 127.76, 127.75, 127.71 (CH-arom), 106.19, 106.15 (C(2)), 83.17, 79.80 (C(6a)), 77.49, 76.46 (C(4)), 75.64, 74.41 (C(6)), 54.34, 54.25 (MeO), 51.48, 50.17 (C(3a)), 38.05, 37.98 (C(3)), 36.96, 36.21 (C(5)), 26.95, 26.90 (CH<com:Sub>3< / com:Sub>)<com:Sub>3< / com:Sub>-C- Si), 21.09, 21.04 (MeCO<com:Sub>2< / com:Sub>), 19.04 (CH<com:Sub>3< / com:Sub>)<com:Sub>3< / com:Sub>-C-Si). <com:Math><semantics>ESI+<annotation encoding="application / x-tex">ESI^{+}< / annotation>< / semantics>< / com:Math>-HRMS <com:Math><semantics>m / z<annotation encoding="application / x-tex">m / z< / annotation>< / semantics>< / com:Math> calcd for <com:Math><semantics>C26H34O5NaSi<annotation encoding="application / x-tex">C_{26}H_{34}O_{5}NaSi< / annotation>< / semantics>< / com:Math> ([M + Na]<com:Sup>+< / com:Sup>) 477.2068, found 477.2063. EXAMPLE 8 (3aR,4R,6R,6aS)-4-((tert-butyldiphenylsilyl)oxy)-3a,5,6,6a-tetrahydro-4H- cyclopenta[b]furan-6-ol (8) [Image disponible dans le document PDF, Image available in the PDF document] b 8 To a solution of the sugar 6 (2.08 g, 5.04 mmol) in dry DCM (35 mL) was added 2,6- lutidine (2.95 mL, 25.2 mmol) at 0°C. After stirring for 20 min at 0°C, TMSOTf (2.73 mL, 15.1 mmol) was added dropwise and then the solution was allowed to warm to rt and stirred for another 60 min. The reaction was then quenched by addition of satd NaHCO<com:Sub>3< / com:Sub> (40 mL). The organic phase was separated and aqueous phase was further extracted with DCM (3 X 30) mL). The combined organic phases were dried over MgSO<com:Sub>4< / com:Sub>, filtered and evaporated. The resulting product was dissolved in dry THF (35 mL), cool down to 0°C, and TBAF (1M in THF, 5.6 mL, 5.6 mmol) was added. The solution was stirred for 10 min and then diluted with satd NaHCO<com:Sub>3< / com:Sub> (30 mL) and extracted with DCM (4 X 40 mL). The combined organic phases were dried over MgSO<com:Sub>4< / com:Sub>, filtered and evaporated. The crude product was purified by CC (EtOAc / hexane 1:4) to yield the glycal 8 (1.76 g, 92%). Data for 8: <com:Math><semantics>Rf=0.49<annotation encoding="application / x-tex">R_f = 0.49< / annotation>< / semantics>< / com:Math> (EtOAc / hexane 1:2); <com:Sup>1< / com:Sup>H NMR (300 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.66 (m, 4H, H-arom), 7.42 (m, 6H, H-arom), 6.22 (t, <com:Math><semantics>J=<annotation encoding="application / x-tex">J =< / annotation>< / semantics>< / com:Math> 2.1 Hz, 1H, H-C(2)), 4.91 (dd, <com:Math><semantics>J=8.2<annotation encoding="application / x-tex">J = 8.2< / annotation>< / semantics>< / com:Math>, 5.3 Hz, 1H, H-C(3)), 4.70 (dt, <com:Math><semantics>J=11.1<annotation encoding="application / x-tex">J = 11.1< / annotation>< / semantics>< / com:Math>, 5.6 Hz, 1H, H- <com:Math><semantics>C(6)<annotation encoding="application / x-tex">C(6)< / annotation>< / semantics>< / com:Math>), 4.56 (t, <com:Math><semantics>J=2.8<annotation encoding="application / x-tex">J = 2.8< / annotation>< / semantics>< / com:Math> Hz, 1H, H-<com:Math><semantics>C(6a)<annotation encoding="application / x-tex">C(6a)< / annotation>< / semantics>< / com:Math>), 3.97 (d, <com:Math><semantics>J=4.0<annotation encoding="application / x-tex">J = 4.0< / annotation>< / semantics>< / com:Math> Hz, 1H, H-<com:Math><semantics>C(4)<annotation encoding="application / x-tex">C(4)< / annotation>< / semantics>< / com:Math>), 3.24 (d, <com:Math><semantics>J=8.2<annotation encoding="application / x-tex">J = 8.2< / annotation>< / semantics>< / com:Math> Hz, 1H, H-C(3a)), 2.30 (br, 1H, OH), 2.03 (dd, <com:Math><semantics>J=12.6<annotation encoding="application / x-tex">J = 12.6< / annotation>< / semantics>< / com:Math>, 5.4 Hz, 1H, H-C(5)), 1.51 (ddd, <com:Math><semantics>J=12.7<annotation encoding="application / x-tex">J = 12.7< / annotation>< / semantics>< / com:Math>, 11.2, 4.2 Hz, 1H, H-C(5)), 1.08 (s, 9H, <com:Math><semantics>(CH3)3<annotation encoding="application / x-tex">(CH_3)_3< / annotation>< / semantics>< / com:Math>-C-Si). <com:Sup>13< / com:Sup>C NMR (75 MHz, CDCl<com:Sub>3< / com:Sub>) δ 146.24 (C(2)), 135.72, 135.69 (CH-arom), 134.03, 133.74 (C-arom), 129.80, 129.78, 127.73 (CH-arom), 101.84 (C(3)), 84.59 (C(6a)), 76.79(C(4)), 74.10 (C(6)), 55.56 (C(3a)), 39.38 (C(5)), 26.93 (<com:Math><semantics>CH3<annotation encoding="application / x-tex">CH_3< / annotation>< / semantics>< / com:Math>)<com:Sub>3< / com:Sub>-C-Si), 19.08 (<com:Math><semantics>CH3<annotation encoding="application / x-tex">CH_3< / annotation>< / semantics>< / com:Math>)<com:Sub>3< / com:Sub>-<com:Math><semantics>C<annotation encoding="application / x-tex">C< / annotation>< / semantics>< / com:Math>-Si). <com:Math><semantics>ESI+<annotation encoding="application / x-tex">ESI^{+}< / annotation>< / semantics>< / com:Math>-HRMS <com:Math><semantics>m / z<annotation encoding="application / x-tex">m / z< / annotation>< / semantics>< / com:Math> calcd for <com:Math><semantics>C23H29O3Si([M+H]+)<annotation encoding="application / x-tex">C_{23}H_{29}O_{3}Si([M + H]^{+})< / annotation>< / semantics>< / com:Math> 381.1880, found 381.1893. EXAMPLE 9 (((3aR,4R,6R,6aS)-6-(bis(4-methoxyphenyl)(phenyl)methoxy)-3a,5,6,6a-tetrahydro-4H- cyclopenta[b]furan-4-yl)oxy)(tert-butyl)diphenylsilane (9) [Image disponible dans le document PDF, Image available in the PDF document] To a solution of glycal 8 (1.34 g, 3.52 mmol) and DMTr-Cl (1.43 g, 4.23 mmol) in a mixture of dry DCM (15 mL) and dry 2,6-lutidine (15 mL) was added portionwise silver triflate (1.13 g, 4.40 mmol), resulting in a deep red suspension. After stirring for 2 hours at rt, an additional portion of DMTr-Cl (239 mg, 0.705 mmol) was added. The suspension was further stirred for 2 hours and then was filtered. The organic phase was washed with satd NaHCO<com:Sub>3< / com:Sub> (100 mL) and aqueous phase were extracted with DCM (3 X 30 mL). The combined organic phases were dried over MgSO<com:Sub>4< / com:Sub>, filtered and evaporated. The crude product was purified by CC (EtOAc / hexane 1:7, +0.5 % Et<com:Sub>3< / com:Sub>N) to yield the protected glycal 9 (2.24, 93%) as a white foam. Data for 9: <com:Math><semantics>Rf=0.59<annotation encoding="application / x-tex">R_f = 0.59< / annotation>< / semantics>< / com:Math> (EtOAc / hexane 1:2); <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 7.76 (d, <com:Math><semantics>J=7.4<annotation encoding="application / x-tex">J = 7.4< / annotation>< / semantics>< / com:Math> Hz, 2H, H-arom), 7.69 – 7.60 (m, <com:Math><semantics>J=<annotation encoding="application / x-tex">J =< / annotation>< / semantics>< / com:Math> 9.3, 5.9, 4.6 Hz, 8H, H-arom), <com:Math><semantics>7.56−7.39<annotation encoding="application / x-tex">7.56 - 7.39< / annotation>< / semantics>< / com:Math> (m, 8H, H-arom), <com:Math><semantics>7.33<annotation encoding="application / x-tex">7.33< / annotation>< / semantics>< / com:Math> (t, <com:Math><semantics>J=7.3<annotation encoding="application / x-tex">J = 7.3< / annotation>< / semantics>< / com:Math> Hz, 1H, H-arom), <com:Math><semantics>7.00−6.93<annotation encoding="application / x-tex">7.00 - 6.93< / annotation>< / semantics>< / com:Math> (m, 4H, H-arom), <com:Math><semantics>6.47−6.37<annotation encoding="application / x-tex">6.47 - 6.37< / annotation>< / semantics>< / com:Math> (m, 1H, H-C(2)), <com:Math><semantics>4.67−4.58<annotation encoding="application / x-tex">4.67 - 4.58< / annotation>< / semantics>< / com:Math> (m, 1H, H-C(6)), <com:Math><semantics>4.58<annotation encoding="application / x-tex">4.58< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−4.50<annotation encoding="application / x-tex">-4.50< / annotation>< / semantics>< / com:Math> (m, 2H, H-C(3), H-C(6a)), 3.86, 3.85 (2s, 6H, MeO), 3.82 (d, <com:Math><semantics>J=4.0<annotation encoding="application / x-tex">J = 4.0< / annotation>< / semantics>< / com:Math> Hz, 1H, H-C(4)), <com:Math><semantics>3.08(d,J=8.1Hz,1H,H−C(3a)),1.67(td,J=12.4,4.2Hz,1H,H−C(5)),1.28(dd,J=12.7,1.28(dd,J=12.7))<annotation encoding="application / x-tex">3.08 (d, J = 8.1 Hz, 1H, H-C(3a)), 1.67 (td, J = 12.4, 4.2 Hz, 1H, H-C(5)), 1.28 (dd, J = 12.7, 1.28 (dd, J = 12.7))< / annotation>< / semantics>< / com:Math> 5.4 Hz, 1H, H-C(5)), 1.11 (s, 9H, <com:Math><semantics>(CH3)3<annotation encoding="application / x-tex">(CH_3)_3< / annotation>< / semantics>< / com:Math>-C-Si). <com:Sup>13< / com:Sup>C NMR (75 MHz, CDCl<com:Sub>3< / com:Sub>) δ 158.67 (MeO-C-arom), 147.61 (C(2)), 146.26, 137.36, 137.21 (C-arom), 135.81, 135.78 (CH-arom), 134.17, 134.04 (C-arom), 130.48, 129.83, 129.81, 128.37, 127.98, 127.76, 127.73, 126.79, 113.32, 113.28 (CH-arom), 100.29 (C(3)), 86.96 (C(Ph)<com:Sub>3< / com:Sub>), 84.95 (C(6a)), 76.17 (C(6)), 76.07(C(4)), 55.26 (MeO-DMTr), 55.11 (C(3a)), 37.32 (C(5)), 27.04 (CH<com:Sub>3< / com:Sub>)<com:Sub>3< / com:Sub>-C-Si), 19.21 (CH<com:Sub>3< / com:Sub>)<com:Sub>3< / com:Sub>-C-Si). <com:Math><semantics>ESI+<annotation encoding="application / x-tex">ESI^{+}< / annotation>< / semantics>< / com:Math>-HRMS <com:Math><semantics>m / z<annotation encoding="application / x-tex">m / z< / annotation>< / semantics>< / com:Math> calcd for <com:Math><semantics>C44H46O5NaSi([M+Na]+)<annotation encoding="application / x-tex">C_{44}H_{46}O_{5}NaSi([M + Na]^{+})< / annotation>< / semantics>< / com:Math> 705.3007, found 705.3021. EXAMPLE 10 (3aS,4R,6R,6aS)-6-(bis(4-methoxyphenyl)(phenyl)methoxy)-3a,5,6,6a-tetrahydro-4H- cyclopenta[b]furan-4-ol (10) [Image disponible dans le document PDF, Image available in the PDF document] To a solution of glycal 9 (2.23 g, 3.27 mmol) in dry THF (20 mL) was added TBAF (1M in THF, 20 mL, 20 mmol) at rt. The solution was stirred for 20 h and then was diluted with satd NaHCO<com:Sub>3< / com:Sub> (100 mL) and extracted with DCM (3 X 80 mL). The combined organic phases were dried over MgSO<com:Sub>4< / com:Sub>, filtered and evaporated. The crude product was purified by CC (0.5% MeOH in DCM, <com:Math><semantics>+0.5<annotation encoding="application / x-tex">+0.5< / annotation>< / semantics>< / com:Math> % Et<com:Sub>3< / com:Sub>N) to yield 10 (1.45 g, quant.) as a white foam. Data for 10: <com:Math><semantics>Rf=0.44<annotation encoding="application / x-tex">R_f = 0.44< / annotation>< / semantics>< / com:Math> (EtOAc / hexane 1:1); <com:Sup>1< / com:Sup>H NMR (300 MHz, CDCl<com:Sub>3< / com:Sub>) δ 7.53 – 7.46 (m, 2H, H-arom), 7.43 – 7.35 (m, 4H, H- arom), 7.21 (dd, <com:Math><semantics>J=10.7<annotation encoding="application / x-tex">J = 10.7< / annotation>< / semantics>< / com:Math>, 5.3 Hz, 2 H, H-arom), 7.16 – 7.08 (m, 1H, H-arom), 6.80 – 6.71 (m, 4H, H-arom), 6.30 (t, <com:Math><semantics>J=2.1<annotation encoding="application / x-tex">J = 2.1< / annotation>< / semantics>< / com:Math> Hz, 1H, H-C(2)), 4.68 (t, <com:Math><semantics>J=2.8<annotation encoding="application / x-tex">J = 2.8< / annotation>< / semantics>< / com:Math> Hz, 1H, H-C(3)), 4.29 – 4.14 (m, 2H, H-C(6), H-C(6a)), 3.71 (s, 6H, MeO), 3.65 (d, <com:Math><semantics>J=3.5<annotation encoding="application / x-tex">J = 3.5< / annotation>< / semantics>< / com:Math> Hz, 1H, H-C(4)), 2.87 (d, <com:Math><semantics>J=<annotation encoding="application / x-tex">J =< / annotation>< / semantics>< / com:Math> 7.9 Hz, 1H, H-C(3a)), 1.59 (ddd, <com:Math><semantics>J=13.2<annotation encoding="application / x-tex">J = 13.2< / annotation>< / semantics>< / com:Math>, 11.6, 4.3 Hz, 1H, H-C(5)), 1.05 – 0.95 (m, 2H, H- <com:Math><semantics>C(5)<annotation encoding="application / x-tex">C(5)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>OH<annotation encoding="application / x-tex">OH< / annotation>< / semantics>< / com:Math>). <com:Sup>13< / com:Sup>C NMR (75 MHz, CDCl<com:Sub>3< / com:Sub>) δ 158.54 (MeO-C-arom), 147.64 (C(2)), 145.82, 137.12, 137.08 (C-arom), 130.26, 128.29, 127.81, 126.71, 113.13 (CH-arom), 100.17 (C(3)), 86.75 (C(Ph)<com:Sub>3< / com:Sub>), 84.42 C(6a)), 75.54 (C(6)), 74.59 (C(4)), 55.22 (MeO-DMTr), 54.25 (C(3a)), 37.56 (C(5)). <com:Math><semantics>ESI+<annotation encoding="application / x-tex">ESI^{+}< / annotation>< / semantics>< / com:Math>-HRMS <com:Math><semantics>m / z<annotation encoding="application / x-tex">m / z< / annotation>< / semantics>< / com:Math> calcd for <com:Math><semantics>C30H27O5<annotation encoding="application / x-tex">C_{30}H_{27}O_{5}< / annotation>< / semantics>< / com:Math> ([M + H]<com:Sup>+< / com:Sup>) 467.1853, found 467.1844. EXAMPLE 11 (3'S,5'R,7'R)-1-{2',3'-Dideoxy-3',5'-ethano-7'-hydroxy-5'-O-[(4,4'- <com:Math><semantics>dimethoxytriphenyl)methyl]−β−D−ribofuranosyl}thymine(11)<annotation encoding="application / x-tex">dimethoxytriphenyl)methyl]-\beta-D-ribofuranosyl\} thymine (11)< / annotation>< / semantics>< / com:Math> [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] 1) BSA, Thymine, NIS, DCM 2) Bu<com:Sub>3< / com:Sub>SnH, AlBN, TBAF, Tol To a solution of glycal 10 (1.45 g, 3.27 mmol) in dry DCM (45 mL), at 0°, was added dropwise BSA (2.0 mL, 8.18 mmol) and then the solution was allowed to warm to rt. After stirring for 45 min, Thymine (595 mg, 4.91 mmol) was added and the reaction was further stirred for 60 min at rt. The mixture was then cooled down to 0° C and N-iodosuccinimide (875 mg, 3.92 mmol) was added. After stirring for 3 h at 0° C and for 4 h at rt, the reaction mixture was diluted with EtOAc (100 mL) and subsequently washed with a 10% aq solution of Na<com:Sub>2< / com:Sub>S<com:Sub>2< / com:Sub>O<com:Sub>3< / com:Sub> (100 mL) and satd NaHCO<com:Sub>3< / com:Sub> (100 mL). Aqueous phases were combined and extracted with DCM (3 X 50 mL). The combined organic phases were dried over MgSO<com:Sub>4< / com:Sub>, filtered and evaporated. The crude product was dissolved in dry toluene (45 mL) and then Bu<com:Sub>3< / com:Sub>SnH (1.32 mL, 4.91 mmol) and azoisobutyronitrile (AIBN, 53 mg, 0.33 mmol) were added at rt. After heating at 70°C for 30 min, the mixture was cool down to rt and TBAF was added (1M in THF, 6.5 mL, 6.5 mmol). The solution was further stirred for 25 min and was diluted with satd NaHCO<com:Sub>3< / com:Sub> (100 mL) and extracted with DCM (4 X 70 mL). The combined organic phases were dried over MgSO<com:Sub>4< / com:Sub>, filtered and evaporated. The crude product was purified by CC (3% MeOH in DCM, +0.5 % Et<com:Sub>3< / com:Sub>N) to yield 11 (1.45 g, 73% over two steps) as a white foam. Data for 11: <com:Math><semantics>Rf=0.29<annotation encoding="application / x-tex">R_f = 0.29< / annotation>< / semantics>< / com:Math> (6% MeOH in DCM); <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 9.37 (br, 1H, H-N(3)), 7.83 (d, <com:Math><semantics>J=1.1<annotation encoding="application / x-tex">J = 1.1< / annotation>< / semantics>< / com:Math> Hz, 1H, H-C(6)), <com:Math><semantics>7.58−7.52<annotation encoding="application / x-tex">7.58 - 7.52< / annotation>< / semantics>< / com:Math> (m, 2H, H-arom), <com:Math><semantics>7.48−7.41<annotation encoding="application / x-tex">7.48 - 7.41< / annotation>< / semantics>< / com:Math> (m, 4H, H-arom), <com:Math><semantics>7.28<annotation encoding="application / x-tex">7.28< / annotation>< / semantics>< / com:Math> (t, <com:Math><semantics>J=7.7<annotation encoding="application / x-tex">J = 7.7< / annotation>< / semantics>< / com:Math> Hz, 2H, H-arom), 7.21 (t, <com:Math><semantics>J=7.2<annotation encoding="application / x-tex">J = 7.2< / annotation>< / semantics>< / com:Math> Hz, 1H, H-arom), 6.84 (dd, <com:Math><semantics>J=8.9<annotation encoding="application / x-tex">J = 8.9< / annotation>< / semantics>< / com:Math>, 1.2 Hz, 4H, H-arom), 5.91 (dd, <com:Math><semantics>J=8.0<annotation encoding="application / x-tex">J = 8.0< / annotation>< / semantics>< / com:Math>, 5.5 Hz, 1H, H-C(1')), 4.25 (dt, <com:Math><semantics>J=10.8<annotation encoding="application / x-tex">J = 10.8< / annotation>< / semantics>< / com:Math>, 6.0 Hz, 1H, H-C(5')), 4.13 – 4.08 (m, 1H, H-C(4')), 3.86 <com:Math><semantics>(d,J=3.4 Hz,1H,H−C(7),3.79 (s, 6H, MeO),2.70 (ddd, J=12.8,10.2,5.5 Hz, 1H,H−C(7),3.79 (s, 6H, MeO),2.70 (ddd, J=12.8,10.2,5.5 Hz, 1H,H−C(7),3.79 (s, 6H, MeO),2.<annotation encoding="application / x-tex">(d, J = 3.4 \text{ Hz}, 1H, H-C(7), 3.79 \text{ (s, 6H, } MeO), 2.70 \text{ (ddd, } J = 12.8, 10.2, 5.5 \text{ Hz, } 1H, H-C(7), 3.79 \text{ (s, 6H, } MeO), 2.70 \text{ (ddd, } J = 12.8, 10.2, 5.5 \text{ Hz, } 1H, H-C(7), 3.79 \text{ (s, 6H, } MeO), 2.< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C(2′)<annotation encoding="application / x-tex">C(2')< / annotation>< / semantics>< / com:Math>), 2.61 (dd, <com:Math><semantics>J=16.9<annotation encoding="application / x-tex">J = 16.9< / annotation>< / semantics>< / com:Math>, 8.2 Hz, 1H, H-<com:Math><semantics>C(3′)<annotation encoding="application / x-tex">C(3')< / annotation>< / semantics>< / com:Math>), 1.84 (d, <com:Math><semantics>J=0.8<annotation encoding="application / x-tex">J = 0.8< / annotation>< / semantics>< / com:Math> Hz, 3H, <com:Math><semantics>Me<annotation encoding="application / x-tex">Me< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C(5)<annotation encoding="application / x-tex">C(5)< / annotation>< / semantics>< / com:Math>), 1.80 (br, 1H, OH), 1.60 (ddd, <com:Math><semantics>J=14.2<annotation encoding="application / x-tex">J = 14.2< / annotation>< / semantics>< / com:Math>, 10.5, 4.2 Hz, 1H, H-C(6')), 1.33 (dt, <com:Math><semantics>J=12.9<annotation encoding="application / x-tex">J = 12.9< / annotation>< / semantics>< / com:Math>, 8.0 Hz, 1H, H- <com:Math><semantics>C(2′)<annotation encoding="application / x-tex">C(2')< / annotation>< / semantics>< / com:Math>, 1.14 (dd, <com:Math><semantics>J=13.7<annotation encoding="application / x-tex">J = 13.7< / annotation>< / semantics>< / com:Math>, 6.1 Hz, 1H, H-C(6')). <com:Sup>13< / com:Sup>C NMR (101 MHz, CDCl<com:Sub>3< / com:Sub>) δ 164.17 (C(4)), 158.64 (MeO-C-arom), 150.47 (C(2)), 145.65, 136.85, 136.71 (C-arom), 135.52 (C(6)), 130.20, 128.12, 127.91, 126.90, 113.22, 113.21 (CH-arom), 110.69 (C(5)), 87.21 (<com:Math><semantics>C(Ph)3<annotation encoding="application / x-tex">C(Ph)_3< / annotation>< / semantics>< / com:Math>), 86.57 (C(1')), 82.02 (C(4')), 74.19 (C(5')), 74.13 (C(7')), 55.25 (MeO-DMTr), 49.40 (C(3')), 38.51 (C(6')), 37.64 (C(2')), 12.58 (Me- <com:Math><semantics>C(5)<annotation encoding="application / x-tex">C(5)< / annotation>< / semantics>< / com:Math>). <com:Math><semantics>ESI+<annotation encoding="application / x-tex">ESI^{+}< / annotation>< / semantics>< / com:Math>-HRMS <com:Math><semantics>m / z<annotation encoding="application / x-tex">m / z< / annotation>< / semantics>< / com:Math> calcd for <com:Math><semantics>C33H34O7N2Na<annotation encoding="application / x-tex">C_{33}H_{34}O_{7}N_{2}Na< / annotation>< / semantics>< / com:Math> ([M + Na]<com:Sup>+< / com:Sup>) 593.2258, found 593.2250. EXAMPLE 12 (3'R,5'R,7'R)-1-{7'-O-[(2-cyanoethoxy)-diisopropylaminophosphanyl]-2',3'-Dideoxy-3',5'- ethano-5'-O-[(4,4'-dimethoxytriphenyl)methyl]-β-D-ribofuranosyl} thymine (12) [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] 11 To a solution of the nucleoside 11 (232 mg, 0.406 mmol) and 5-(Ethylthio)-1H-tetrazole (90 mg, 0.69 mmol) in dry DCM (10 mL) was added dropwise 2-Cyanoethyl N,N,N',N'- tetraisopropylphosphordiamidite (0.26 mL, 0.81 mmol) at rt. After stirring for 30 min, the reaction mixture was diluted with DCM (50 mL) and washed with satd NaHCO<com:Sub>3< / com:Sub> (2 X 30 mL) and satd NaCl (30 mL). Aqueous phases were combined and extracted with DCM (50 mL). The combined organic phases were dried over MgSO<com:Sub>4< / com:Sub>, filtered and evaporated. The crude product was purified by CC (1.8% MeOH in DCM, +0.5 % Et<com:Sub>3< / com:Sub>N) to yield 12 (219 mg, mixture of two isomers, 70%) as a white foam. Data for 11: <com:Math><semantics>Rf=0.68<annotation encoding="application / x-tex">R_f = 0.68< / annotation>< / semantics>< / com:Math> (6% MeOH in DCM); <com:Sup>1< / com:Sup>H NMR (300 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 8.93 (br, 1H, H-N(3)), 7.85 (d, <com:Math><semantics>J=1.2<annotation encoding="application / x-tex">J = 1.2< / annotation>< / semantics>< / com:Math> Hz, 1H, H-C(6)), <com:Math><semantics>7.65−7.52<annotation encoding="application / x-tex">7.65 - 7.52< / annotation>< / semantics>< / com:Math> (m, 2H, H-arom), <com:Math><semantics>7.52−7.40<annotation encoding="application / x-tex">7.52 - 7.40< / annotation>< / semantics>< / com:Math> (m, 4H, H-arom), <com:Math><semantics>7.40−7.21<annotation encoding="application / x-tex">7.40 - 7.21< / annotation>< / semantics>< / com:Math> (m, 3H, H-arom), <com:Math><semantics>6.96−6.81<annotation encoding="application / x-tex">6.96 - 6.81< / annotation>< / semantics>< / com:Math> (m, 4H, H-arom), <com:Math><semantics>6.00<annotation encoding="application / x-tex">6.00< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>5.94<annotation encoding="application / x-tex">5.94< / annotation>< / semantics>< / com:Math> (2dd, <com:Math><semantics>J=8.3<annotation encoding="application / x-tex">J = 8.3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>5.2<annotation encoding="application / x-tex">5.2< / annotation>< / semantics>< / com:Math> Hz, 1H, H-C(1')), <com:Math><semantics>4.29−4.17<annotation encoding="application / x-tex">4.29 - 4.17< / annotation>< / semantics>< / com:Math> (m, 1H, H-C(5')), <com:Math><semantics>4.12−3.89<annotation encoding="application / x-tex">4.12 - 3.89< / annotation>< / semantics>< / com:Math> (m, 2H, H-C(4'), H-C(7')), <com:Math><semantics>3.85<annotation encoding="application / x-tex">3.85< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>3.84<annotation encoding="application / x-tex">3.84< / annotation>< / semantics>< / com:Math> (2s, 6H, MeO), <com:Math><semantics>3.81−3.63<annotation encoding="application / x-tex">3.81 - 3.63< / annotation>< / semantics>< / com:Math> (m, 2H, OC<com:Math><semantics>H2<annotation encoding="application / x-tex">H_2< / annotation>< / semantics>< / com:Math>CH<com:Sub>2< / com:Sub>CN), 3.56 – 3.41 (m, 2H, (Me<com:Sub>2< / com:Sub>C<com:Math><semantics>H<annotation encoding="application / x-tex">H< / annotation>< / semantics>< / com:Math>)<com:Sub>2< / com:Sub>N), 2.88 – 2.69 (m, 2H, H-C(3'), H- <com:Math><semantics>C(2′)<annotation encoding="application / x-tex">C(2')< / annotation>< / semantics>< / com:Math>), 2.61, 2.56 (dt, <com:Math><semantics>J=12.9<annotation encoding="application / x-tex">J = 12.9< / annotation>< / semantics>< / com:Math> 6.3 Hz, 2H, <com:Math><semantics>OCH2CH2CN<annotation encoding="application / x-tex">OCH_2CH_2CN< / annotation>< / semantics>< / com:Math>), 1.92, 1.82 (2d, <com:Math><semantics>J=0.8<annotation encoding="application / x-tex">J = 0.8< / annotation>< / semantics>< / com:Math> Hz, 3H, <com:Math><semantics>Me<annotation encoding="application / x-tex">Me< / annotation>< / semantics>< / com:Math>- <com:Math><semantics>C(5)<annotation encoding="application / x-tex">C(5)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>1.75−1.56<annotation encoding="application / x-tex">1.75 - 1.56< / annotation>< / semantics>< / com:Math> (m, 1H, H-<com:Math><semantics>C(6)<annotation encoding="application / x-tex">C(6)< / annotation>< / semantics>< / com:Math>), <com:Math><semantics>1.52−1.36<annotation encoding="application / x-tex">1.52 - 1.36< / annotation>< / semantics>< / com:Math> (m, 2H, H-<com:Math><semantics>C(6)<annotation encoding="application / x-tex">C(6)< / annotation>< / semantics>< / com:Math>), <com:Math><semantics>H−C(2)<annotation encoding="application / x-tex">H-C(2)< / annotation>< / semantics>< / com:Math>), <com:Math><semantics>1.22−1.01<annotation encoding="application / x-tex">1.22 - 1.01< / annotation>< / semantics>< / com:Math> (m, 12H, <com:Math><semantics>(Me2CH)2N<annotation encoding="application / x-tex">(Me_2CH)_2N< / annotation>< / semantics>< / com:Math>). <com:Sup>13< / com:Sup>C NMR (101 MHz, CDCl<com:Sub>3< / com:Sub>) δ 163.86 (C(4)), 158.66, 158.64 (MeO-C-arom), 150.29, 150.27 (C(2)), 145.58, 145.52, 136.76, 136.71, 136.69, 136.60 (C-arom), 135.49, 135.35 (C(6)), 130.21, 130.16, 128.17, 128.13, 127.88, 126.91, 126.89 (CH-arom), 117.49 <com:Math><semantics>(OCH2CH2CN)<annotation encoding="application / x-tex">(OCH_2CH_2CN)< / annotation>< / semantics>< / com:Math>, 113.18 (CH-arom), 110.74 (C(5)), 87.27, 87.25 (C(Ph)<com:Sub>3< / com:Sub>), 86.58, 86.45 <com:Math><semantics>(C(1′))<annotation encoding="application / x-tex">(C(1'))< / annotation>< / semantics>< / com:Math>, 81.79, 81.68 <com:Math><semantics>(C(4′))<annotation encoding="application / x-tex">(C(4'))< / annotation>< / semantics>< / com:Math>, 76.02, 75.50 <com:Math><semantics>(JC,P=16.5,15.7 Hz,C(7′))<annotation encoding="application / x-tex">(J_{C,P} = 16.5, 15.7 \text{ Hz}, C(7'))< / annotation>< / semantics>< / com:Math>, 74.22 <com:Math><semantics>(C(5′))<annotation encoding="application / x-tex">(C(5'))< / annotation>< / semantics>< / com:Math>, 58.26, 58.06, 57.87 (OCH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>CN), 55.26, 55.22 (MeO-DMTr), 48.85, 48.62 (<com:Math><semantics>JC,P=2.6<annotation encoding="application / x-tex">J_{C,P} = 2.6< / annotation>< / semantics>< / com:Math>, 5.0 Hz, <com:Math><semantics>C(3′)<annotation encoding="application / x-tex">C(3')< / annotation>< / semantics>< / com:Math>), 43.10, 43.04 (<com:Math><semantics>JC,P=12.3<annotation encoding="application / x-tex">J_{C,P} = 12.3< / annotation>< / semantics>< / com:Math>, 12.4 Hz (<com:Math><semantics>Me2CH<annotation encoding="application / x-tex">Me_2CH< / annotation>< / semantics>< / com:Math>)<com:Sub>2< / com:Sub>N), 37.78 (<com:Math><semantics>JC,P=5.3<annotation encoding="application / x-tex">J_{C,P} = 5.3< / annotation>< / semantics>< / com:Math> Hz <com:Math><semantics>C(6′)<annotation encoding="application / x-tex">C(6')< / annotation>< / semantics>< / com:Math>), 37.62, 37.48 (C(2')), 37.41 (<com:Math><semantics>JC,P=3.6 Hz C(6′)<annotation encoding="application / x-tex">J_{C,P} = 3.6 \text{ Hz C}(6')< / annotation>< / semantics>< / com:Math>), 24.57, 24.53, 24.50, 24.46, 24.44, 24.39, 24.37 <com:Math><semantics>(Me2CH)2N<annotation encoding="application / x-tex">(Me_2CH)_2N< / annotation>< / semantics>< / com:Math>), 20.35, 20.25 (<com:Math><semantics>JC,P=7.1<annotation encoding="application / x-tex">J_{C,P} = 7.1< / annotation>< / semantics>< / com:Math>, 7.0 Hz, OCH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>CN), 12.58, 12.41 (7s, Me-C(5)). <com:Sup>31< / com:Sup>P NMR (122 MHz, CDCl<com:Sub>3< / com:Sub>) δ 147.32, 146.98. <com:Math><semantics>ESI+<annotation encoding="application / x-tex">ESI^{+}< / annotation>< / semantics>< / com:Math>-HRMS <com:Math><semantics>m / z<annotation encoding="application / x-tex">m / z< / annotation>< / semantics>< / com:Math> calcd for <com:Math><semantics>C42H52O8N4P<annotation encoding="application / x-tex">C_{42}H_{52}O_{8}N_{4}P< / annotation>< / semantics>< / com:Math> ([M + H]<com:Sup>+< / com:Sup>) 771.3517, found 771.3512. EXAMPLE 13 (3'S,5'R,7'R)-N4-Benzoyl-1-{2',3'-Dideoxy-3',5'-ethano-7'-hydroxy-5'-O-[(4,4'- <com:Math><semantics>dimethoxytriphenyl)methyl]−β−D−ribofuranosyl}−5−methylcytosine(13)<annotation encoding="application / x-tex">dimethoxytriphenyl)methyl]-\beta-D-ribofuranosyl\}-5-methylcytosine (13)< / annotation>< / semantics>< / com:Math> [Image disponible dans le document PDF, Image available in the PDF document] 1) BSA, 1,2,4-triazole, POCl<com:Sub>3< / com:Sub>, [Image disponible dans le document PDF, Image available in the PDF document] Et<com:Sub>3< / com:Sub>N DCM 2) Dioxane, conc NH₄OH 3) Bz<com:Sub>2< / com:Sub>O, Et<com:Sub>3< / com:Sub>N, DMF To a solution of the nucleoside 11 (302 mg, 0.530 mmol) in dry MeCN (5 mL) was added dropwise BSA (0.31 mL, 1.27 mmol) at 0°, and then the solution was stirred overnight at rt. In another flask, a suspension of 1,2,4-triazole (1.28 g, 18.55 mmol) in dry MeCN (50 mL) was cool down to 0° C and POCl<com:Sub>3< / com:Sub> (0.40 mL, 4.2 mmol) and Et<com:Sub>3< / com:Sub>N (2.96 mL, 21.2 mmol) were added. The suspension was stirred for 30 min at 0° C, and then the previous prepared solution of the silylated compound 11 was added to the suspension and the mixture was further stirred for 5 h at rt. Reaction was quenched with addition satd NaHCO<com:Sub>3< / com:Sub> (10 mL), MeCN removed under reduced pressure and the resulting mixture diluted with satd NaHCO<com:Sub>3< / com:Sub> (35 mL) and extracted with DCM (3 X 40 mL). The combined organic phases were dried over MgSO<com:Sub>4< / com:Sub>, filtered and evaporated. The crude product was then dissolved in a mixture of 1,4-dioxane (10 mL) and concd NH<com:Sub>4< / com:Sub>OH (10 mL). After stirring for 2 h at rt, the mixture was reduced to half of the volume in vacuo, diluted with satd NaHCO<com:Sub>3< / com:Sub> (30 mL) and extracted with DCM (4 X 30 mL). The combined organic phases were dried over MgSO<com:Sub>4< / com:Sub>, filtered and evaporated. The crude product was then dissolved in dry DMF (13 mL), Et<com:Sub>3< / com:Sub>N (90 µL, 0.64 mmol) followed by Bz<com:Sub>2< / com:Sub>O (300 mg, 1.33 mmol) were added at rt and the solution was stirred overnight. The resulting brown solution was quenched by careful addition of satd NaHCO<com:Sub>3< / com:Sub> (50 mL) and extracted with DCM (4 X 50 mL). The combined organic phases were dried over MgSO<com:Sub>4< / com:Sub>, filtered and evaporated. The crude product was purified by CC (hexane / EtOAc 1:2, <com:Math><semantics>+0.5%<annotation encoding="application / x-tex">+0.5\%< / annotation>< / semantics>< / com:Math> Et<com:Sub>3< / com:Sub>N) to yield 13 (315 mg, 88%) as a white foam. Data for 13: <com:Math><semantics>Rf=0.57<annotation encoding="application / x-tex">R_f = 0.57< / annotation>< / semantics>< / com:Math> (4% MeOH in DCM); <com:Sup>1< / com:Sup>H NMR (300 MHz, CDCl<com:Sub>3< / com:Sub>) δ 13.39 (br, 1H, NH), 8.46 – 8.26 (m, 2H, H-arom), 8.13 <com:Math><semantics>(d,J=0.5 Hz,1H,C(6)),7.61(d,J=7.3 Hz,2H,H−arom),7.58−7.43(m,7H,H−arom),<annotation encoding="application / x-tex">(d, J = 0.5 \text{ Hz}, 1H, C(6)), 7.61 (d, J = 7.3 \text{ Hz}, 2H, H-arom), 7.58 - 7.43 (m, 7H, H-arom),< / annotation>< / semantics>< / com:Math> 7.34 (t, <com:Math><semantics>J=7.4<annotation encoding="application / x-tex">J = 7.4< / annotation>< / semantics>< / com:Math> Hz, 2H, H-arom), 7.30 – 7.23 (m, 1H, H-arom), 6.89 (d, <com:Math><semantics>J=8.8<annotation encoding="application / x-tex">J = 8.8< / annotation>< / semantics>< / com:Math> Hz, 4H, H- arom), 5.96 (dd, <com:Math><semantics>J=7.5<annotation encoding="application / x-tex">J = 7.5< / annotation>< / semantics>< / com:Math>, 5.8 Hz, 1H, H-C(1')), <com:Math><semantics>4.38−4.25<annotation encoding="application / x-tex">4.38 - 4.25< / annotation>< / semantics>< / com:Math> (m, 1H, H-C(5')), <com:Math><semantics>4.22−4.12<annotation encoding="application / x-tex">4.22 - 4.12< / annotation>< / semantics>< / com:Math> (m, 1H, H-C(4')), 3.90 (d, <com:Math><semantics>J=3.6<annotation encoding="application / x-tex">J = 3.6< / annotation>< / semantics>< / com:Math> Hz, 1H, H-C(7')), 3.83 (s, 6H, MeO), 2.82 (ddd, <com:Math><semantics>J=13.3<annotation encoding="application / x-tex">J = 13.3< / annotation>< / semantics>< / com:Math>, 10.2, 5.7 Hz, 1H, H-C(2')), 2.66 (dd, <com:Math><semantics>J=17.0<annotation encoding="application / x-tex">J = 17.0< / annotation>< / semantics>< / com:Math>, 8.1 Hz, 1H, H-C(3')), 2.08 (s, 3H, <com:Math><semantics>Me<annotation encoding="application / x-tex">Me< / annotation>< / semantics>< / com:Math>-C(5)), 1.77 <com:Math><semantics>(br,1H,OH),1.71−1.57 (m, 1H,H−C(6′)),1.49−1.36 (m, 1H,H−C(2′)),1.21 (dd, J=13.7,)<annotation encoding="application / x-tex">(br, 1H, OH), 1.71 - 1.57 \text{ (m, } 1H, H-C(6')), 1.49 - 1.36 \text{ (m, } 1H, H-C(2')), 1.21 \text{ (dd, } J = 13.7, )< / annotation>< / semantics>< / com:Math> 6.2 Hz, 1H, H-C(6')). <com:Sup>13< / com:Sup>C NMR (75 MHz, CDCl<com:Sub>3< / com:Sub>) δ 179.56 (CONH), 160.01 (C(4)), 158.70 (MeO-C-arom), 147.96 (C(2)), 145.65 (C-arom), 137.26 (C(6)), 136.99, 136.83, 136.71 (C-arom), 132.41, 130.22, 129.89, 128.16, 128.14, 127.95, 126.94, 113.25 (CH-arom), 111.57 (C(5)), 87.34 <com:Math><semantics>(C(Ph)3)<annotation encoding="application / x-tex">(C(Ph)_3)< / annotation>< / semantics>< / com:Math>, 87.32 <com:Math><semantics>(C(1′))<annotation encoding="application / x-tex">(C(1'))< / annotation>< / semantics>< / com:Math>, 82.57 <com:Math><semantics>(C(4′))<annotation encoding="application / x-tex">(C(4'))< / annotation>< / semantics>< / com:Math>, 74.30 <com:Math><semantics>(C(5′))<annotation encoding="application / x-tex">(C(5'))< / annotation>< / semantics>< / com:Math>, 74.16 <com:Math><semantics>(C(7′))<annotation encoding="application / x-tex">(C(7'))< / annotation>< / semantics>< / com:Math>, 55.27 <com:Math><semantics>(MeO−DMTr)<annotation encoding="application / x-tex">(MeO-DMTr)< / annotation>< / semantics>< / com:Math>, 49.56 (C(3')), 38.52 (C(6')), 38.00 (C(2')), 13.63 (Me-C(5)). <com:Math><semantics>ESI+<annotation encoding="application / x-tex">ESI^{+}< / annotation>< / semantics>< / com:Math>-HRMS <com:Math><semantics>m / z<annotation encoding="application / x-tex">m / z< / annotation>< / semantics>< / com:Math> calcd for <com:Math><semantics>C40H40O7N3<annotation encoding="application / x-tex">C_{40}H_{40}O_{7}N_{3}< / annotation>< / semantics>< / com:Math> ([M + H]<com:Sup>+< / com:Sup>) 674.2861, found 674.2862. EXAMPLE 14 (3'R,5'R,7'R)-N4-Benzoyl-1-{7'-O-[(2-cyanoethoxy)-diisopropylaminophosphanyl]-2',3'- Dideoxy-3',5'-ethano-5'-O-[(4,4'-dimethoxytriphenyl)methyl]-β-D-ribofuranosyl}-5- methylcytosine (14) [Image disponible dans le document PDF, Image available in the PDF document] To a solution of the nucleoside 13 (276 mg, 0.409 mmol) and 5-(Ethylthio)-1H-tetrazole (69 mg, 0.53 mmol) in dry DCM (10 mL) was added dropwise 2-Cyanoethyl N,N,N',N'- tetraisopropylphosphordiamidite (0.20 mL, 0.61 mmol) at rt. After stirring for 60 min, the reaction mixture was diluted with DCM (50 mL) and washed with satd NaHCO<com:Sub>3< / com:Sub> (2 X 30 mL) and satd NaCl (30 mL). Aqueous phases were combined and extracted with DCM (50 mL). The combined organic phases were dried over MgSO<com:Sub>4< / com:Sub>, filtered and evaporated. The crude product was purified by CC (EtOAc / Hexanne 2:3, +0.5 % Et<com:Sub>3< / com:Sub>N) to yield 14 (268 mg, mixture of two isomers, 75%) as a white foam. Data for 14: <com:Math><semantics>Rf=0.77<annotation encoding="application / x-tex">R_f = 0.77< / annotation>< / semantics>< / com:Math> (5% MeOH in DCM); <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) δ 13.32 (s, 1H, NH), 8.41 – 8.28 (m, 2H, H-arom), 8.13 – <com:Math><semantics>8.04<annotation encoding="application / x-tex">8.04< / annotation>< / semantics>< / com:Math> (m, 1H, C(6)), <com:Math><semantics>7.61−7.51<annotation encoding="application / x-tex">7.61 - 7.51< / annotation>< / semantics>< / com:Math> (m, 3H, H-arom), <com:Math><semantics>7.51−7.40<annotation encoding="application / x-tex">7.51 - 7.40< / annotation>< / semantics>< / com:Math> (m, 6H, H-arom), <com:Math><semantics>7.37−7.29<annotation encoding="application / x-tex">7.37 - 7.29< / annotation>< / semantics>< / com:Math> <com:Math><semantics>(m,2H,H−arom),7.29−7.20(m,1H,H−arom),6.92−6.82(m,4H,H−arom),6.07−5.87(m,2H,2H,2H,2H,2H,2H,2H,2H,2H,2H<annotation encoding="application / x-tex">(m, 2H, H-arom), 7.29 - 7.20 (m, 1H, H-arom), 6.92 - 6.82 (m, 4H, H-arom), 6.07 - 5.87 (m, 2H, 2H, 2H, 2H, 2H, 2H, 2H, 2H, 2H, 2H< / annotation>< / semantics>< / com:Math> 1H, H-C(1')), 4.24 (dq, <com:Math><semantics>J=11.7<annotation encoding="application / x-tex">J = 11.7< / annotation>< / semantics>< / com:Math>, 5.8 Hz, 1H, H-C(5')), 4.13 – 4.00 (m, 1H, H-C(4')), 3.94 <com:Math><semantics>(ddd,J=14.5,10.5,2.8Hz,1H,H−C(7)),3.83,3.82(2s,6H,MeO),3.69(m,2H,2H,2H)<annotation encoding="application / x-tex">(ddd, J = 14.5, 10.5, 2.8 Hz, 1H, H-C(7)), 3.83, 3.82 (2s, 6H, MeO), 3.69 (m, 2H, 2H, 2H)< / annotation>< / semantics>< / com:Math> <com:Math><semantics>OCH2CH2CN)<annotation encoding="application / x-tex">OCH_2CH_2CN)< / annotation>< / semantics>< / com:Math>, 3.53 – 3.40 (m, 2H, <com:Math><semantics>(Me2CH)2N<annotation encoding="application / x-tex">(Me_2CH)_2N< / annotation>< / semantics>< / com:Math>), 2.91 – 2.70 (m, 2H, H-C(2'), H-C(3')), 2.57, 2.53 (2t, <com:Math><semantics>J=6.3<annotation encoding="application / x-tex">J = 6.3< / annotation>< / semantics>< / com:Math> Hz, 2H, OCH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>CN), 2.08, 1.99 (2d, <com:Math><semantics>J=0.6<annotation encoding="application / x-tex">J = 0.6< / annotation>< / semantics>< / com:Math> Hz, 3H, <com:Math><semantics>Me<annotation encoding="application / x-tex">Me< / annotation>< / semantics>< / com:Math>-C(5)), 1.72 <com:Math><semantics>−1.56<annotation encoding="application / x-tex">-1.56< / annotation>< / semantics>< / com:Math> (m, 1H, H-C(6')), <com:Math><semantics>1.54−1.36<annotation encoding="application / x-tex">1.54 - 1.36< / annotation>< / semantics>< / com:Math> (m, 2H, H-C(2'), H-C(6')), <com:Math><semantics>1.10<annotation encoding="application / x-tex">1.10< / annotation>< / semantics>< / com:Math> (m, 12H, <com:Math><semantics>(Me2CH)2N<annotation encoding="application / x-tex">(Me_2CH)_2N< / annotation>< / semantics>< / com:Math>). <com:Sup>13< / com:Sup>C NMR (101 MHz, CDCl<com:Sub>3< / com:Sub>) δ 179.54 (CONH), 159.98 (C(4)), 158.69 (MeO-C-arom), 147.90 (C(2)), 145.58, 145.54 (C-arom), 137.30, 136.93 (C(6)), 136.81, 136.80, 136.73, 136.70, 136.67, 136.60 (C-arom), 132.37, 132.35, 130.22, 130.17, 129.89, 128.17, 128.15, 128.11, 127.93, 126.94 (CH-arom), 117.49 (OCH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>CN), 113.23 (CH-arom), 111.60 <com:Math><semantics>(C(5))<annotation encoding="application / x-tex">(C(5))< / annotation>< / semantics>< / com:Math>, 87.36, 87.35 <com:Math><semantics>(C(Ph)3)<annotation encoding="application / x-tex">(C(Ph)_3)< / annotation>< / semantics>< / com:Math>, 87.33, 87.25 <com:Math><semantics>(C(1))<annotation encoding="application / x-tex">(C(1))< / annotation>< / semantics>< / com:Math>, 82.33, 82.25 <com:Math><semantics>(C(4))<annotation encoding="application / x-tex">(C(4))< / annotation>< / semantics>< / com:Math>, 76.05, 75.52 <com:Math><semantics>(JC,P=<annotation encoding="application / x-tex">(J_{C,P} =< / annotation>< / semantics>< / com:Math> 16.4, 15.6 Hz, <com:Math><semantics>C(7′)<annotation encoding="application / x-tex">C(7')< / annotation>< / semantics>< / com:Math>), 74.32 (<com:Math><semantics>C(5′)<annotation encoding="application / x-tex">C(5')< / annotation>< / semantics>< / com:Math>), 58.18, 57.98 (<com:Math><semantics>JC,P=19.5 Hz OCH2CH2CN<annotation encoding="application / x-tex">J_{C,P} = 19.5 \text{ Hz O}CH_2CH_2CN< / annotation>< / semantics>< / com:Math>), 55.28, 55.24 (MeO-DMTr), 48.93, 48.72 ( <com:Math><semantics>JC,P=2.7<annotation encoding="application / x-tex">J_{C,P} = 2.7< / annotation>< / semantics>< / com:Math>, 4.9 Hz, C(3')), 43.11, 43.05 ( <com:Math><semantics>JC,P=12.4<annotation encoding="application / x-tex">J_{C,P} = 12.4< / annotation>< / semantics>< / com:Math> Hz <com:Math><semantics>(Me2CH)2N)<annotation encoding="application / x-tex">(Me_2CH)_2N)< / annotation>< / semantics>< / com:Math>, 38.02, 37.88 <com:Math><semantics>(C(2′))<annotation encoding="application / x-tex">(C(2'))< / annotation>< / semantics>< / com:Math>, 37.74, 37.40 <com:Math><semantics>(JC,P=5.3,3.4 Hz,C(6′))<annotation encoding="application / x-tex">(J_{C,P} = 5.3, 3.4 \text{ Hz}, C(6'))< / annotation>< / semantics>< / com:Math>, 24.58, 24.54, 24.50, 24.47, 24.40, 24.38 (6s, <com:Math><semantics>Me2CH)2N<annotation encoding="application / x-tex">Me_2CH)_2N< / annotation>< / semantics>< / com:Math>), 20.36, 20.26 (<com:Math><semantics>JC,P=7.1 Hz,OCH2CH2CN)<annotation encoding="application / x-tex">J_{C,P} = 7.1 \text{ Hz}, OCH_2CH_2CN)< / annotation>< / semantics>< / com:Math>,), 13.66, 13.49 (Me-C(5)). <com:Sup>31< / com:Sup>P NMR (122 MHz, CDCl<com:Sub>3< / com:Sub>) δ 147.37, 147.07. <com:Math><semantics>ESI+<annotation encoding="application / x-tex">ESI^{+}< / annotation>< / semantics>< / com:Math>-HRMS <com:Math><semantics>m / z<annotation encoding="application / x-tex">m / z< / annotation>< / semantics>< / com:Math> calcd for <com:Math><semantics>C49H57O8N5P<annotation encoding="application / x-tex">C_{49}H_{57}O_{8}N_{5}P< / annotation>< / semantics>< / com:Math> ([M + H]<com:Sup>+< / com:Sup>) 874.3939, found 874.3937. EXAMPLE 15 (3'R,5'R,7'R)-N6-Benzoyl-9-{5'-O-acetyl-7'-[(tert-butyldiphenylsilyl)oxy]-2',3'-Dideoxy- 3',5'-ethano-α,β-D-ribofuranosyl} adenine (15) [Image disponible dans le document PDF, Image available in the PDF document] To a suspension of sugar 7 (1.86 g, 4.10 mmol) and N<com:Sup>6< / com:Sup>-Benzoyladenine (1.96 g, 8.20 mmol) in dry MeCN (40 mL) was added BSA (4.00 mL, 16.4 mmol) at rt. After stirring for 25 min, the suspension became a clear solution and then was heated to 70°C. TMSOTf (1.48 mL, 8.20 mmol) was added dropwise and the solution was further stirred for 20 min at 70°C. The solution was then cool down to rt, quenched with addition of satd NaHCO<com:Sub>3< / com:Sub> (100 mL) and extracted with EtOAc (4 X 50 mL). The combined organic phases were dried over MgSO<com:Sub>4< / com:Sub>, filtered and evaporated. The crude product was purified by CC (2% MeOH in DCM) to yield a mixture of 15 (1.74 g, 64%) in an anomeric ratio <com:Math><semantics>α / β≈4:1<annotation encoding="application / x-tex">\alpha / \beta \approx 4:1< / annotation>< / semantics>< / com:Math> as a white foam. Data for 15: <com:Math><semantics>Rf=0.33<annotation encoding="application / x-tex">R_f = 0.33< / annotation>< / semantics>< / com:Math> (EtOAc / hexane 4:1); <com:Sup>1< / com:Sup>H NMR (400 MHz, CDCl<com:Sub>3< / com:Sub>) <com:Math><semantics>δ<annotation encoding="application / x-tex">\delta< / annotation>< / semantics>< / com:Math> 9.33 (br, 1H, NH), 8.68 (d, <com:Math><semantics>J=5.4<annotation encoding="application / x-tex">J = 5.4< / annotation>< / semantics>< / com:Math> Hz, 0.8H, H-C(2)), 8.64 (d, <com:Math><semantics>J=5.6<annotation encoding="application / x-tex">J = 5.6< / annotation>< / semantics>< / com:Math> Hz, 0.2H, H-C(2)), 8.10 (d, <com:Math><semantics>J=1.5<annotation encoding="application / x-tex">J = 1.5< / annotation>< / semantics>< / com:Math> Hz, 0.2H. H-C(8)), 7.99 (d, <com:Math><semantics>J=7.3<annotation encoding="application / x-tex">J = 7.3< / annotation>< / semantics>< / com:Math> Hz, 2H, H-arom), 7.95 (s, 0.8H, H-C(8)), 7.63 (t, <com:Math><semantics>J=8.7<annotation encoding="application / x-tex">J = 8.7< / annotation>< / semantics>< / com:Math> Hz, 4H, H-arom), 7.55 (dd, <com:Math><semantics>J=13.0<annotation encoding="application / x-tex">J = 13.0< / annotation>< / semantics>< / com:Math>, 6.4 Hz, 1H, H-arom), <com:Math><semantics>7.50−7.34<annotation encoding="application / x-tex">7.50 - 7.34< / annotation>< / semantics>< / com:Math> (m, 8H, H-arom), <com:Math><semantics>...

Claims

1. A compound of formula (I): [Image disponible dans le document PDF, Image available in the PDF document] (I) wherein one of T 1 T_1 and T 2 T_2 is O R 1 OR_1 or O R 2 OR_2 ; and the other of T 1 T_1 and T 2 T_2 is O R 1 OR_1 or O R 2 OR_2 ; wherein R 1 is H or a hydroxyl protecting group, and R 2 is a phosphorus moiety of the formula (VII): [Image disponible dans le document PDF, Image available in the PDF document] wherein: W represents O, S or Se or W represents an electron pair; R 3 and R 4 are independently of each other H, halogen, OH, OR 5 , NR 6 R 7 , SH, SR 8 , C 1 - C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 aminoalkyl; wherein R 5 is C 1 -C 9 alkyl, optionally substituted with cyano, nitro, halogen, - NHC(O)C 1 -C 3 alkyl, -NHC(O)C 1 -C 3 haloalkyl, C 1 -C 3 alkylsulfonyl; aryl, C 1 - C 6 alkylenearyl, C 1 -C 6 alkylenediaryl, each independently of each other optionally substituted with cyano, nitro, halogen, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, N H C ( O ) C 1 − C 3 NHC(O)C_1-C_3 alkyl, N H C ( O ) C 1 − C 3 NHC(O)C_1-C_3 haloalkyl, C 1 C_1 - C 3 alkylsulfonyl; acetyl; a hydroxyl protecting group; R 6 and R 7 are independently of each other hydrogen, C 1 -C 9 alkyl optionally substituted with cyano, nitro, halogen, C 2 -C 6 alkenyl, C 3 -C 6 cycloalkyl, C 1 -C 3 alkoxy; aryl optionally substituted with cyano, nitro, halogen, C 1 -C 3 alkyl, C 1 -C 3 alkoxy; an amino protecting group; or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein said heterocyclic ring is optionally substituted with C 1 C_1 - C 3 C_3 alkyl; R 8 is a thiol protecting group; and wherein the wavy line indicates the attachment to the oxygen of said OR 2 group; and wherein Bx is a purine base or pyrimidine base.

2. The compound of claim 1, wherein Bx is selected from uracil, thymine, cytosine, 5- methylcytosine, adenine or guanine.

3. The compound of claim 1 or claim 2, wherein said compound of formula (I) is a compound of formula (II) [Image disponible dans le document PDF, Image available in the PDF document] (II) wherein (i) T 1 T_1 is O R 1 OR_1 , and T 2 T_2 is O R 1 OR_1 or O R 2 OR_2 ; or (ii) T 1 T_1 is O R 1 OR_1 or O R 2 OR_2 , T 2 T_2 is O R 1 OR_1 .

4. The compound of claim 3, wherein T 1 T_1 is O R 1 OR_1 or O R 2 OR_2 , T 2 T_2 is O R 1 OR_1 .

5. The compound of claim 1 or claim 2, wherein said compound of formula (I) is a compound of formula (III) [Image disponible dans le document PDF, Image available in the PDF document] (III) wherein (i) T 1 T_1 is O R 1 OR_1 , and T 2 T_2 is O R 1 OR_1 or O R 2 OR_2 ; or (ii) T 1 T_1 is O R 1 OR_1 or O R 2 OR_2 , T 2 T_2 is O R 1 OR_1 .

6. The compound of claim 5, wherein T 1 T_1 is O R 1 OR_1 , and T 2 T_2 is O R 1 OR_1 or O R 2 OR_2 .

7. The compound of any one of the claims 1 to 6, wherein said phosphorus moiety R 2 is selected from a phosphate moiety of the formula (VIII), a phosphoramidate moiety of the formula (IX), and a phosphoramidite moiety of the formula (X): [Image disponible dans le document PDF, Image available in the PDF document] , wherein Y is O, S or Se; R 5 and R 5 , are independently at each occurrence and of each other hydrogen, C 1 -C 9 alkyl, optionally substituted with cyano, nitro, halogen, -NHC(O)C 1 -C 3 alkyl, - NHC(O)C 1 -C 3 haloalkyl, C 1 -C 3 alkylsulfonyl; aryl, C 1 -C 6 alkylenearyl, C 1 - C 6 alkylenediaryl each independently of each other optionally substituted with cyano, nitro, halogen, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, - NHC(O)C 1 -C 3 alkyl, NHC(O)C 1 -C 3 haloalkyl, C 1 -C 3 alkylsulfonyl; a hydroxyl protecting group; wherein R 6 and R 7 are independently of each other hydrogen, C 1 -C 9 alkyl optionally substituted with cyano, nitro, halogen, C2-C6alkenyl, C3-C6cycloalkyl, C1- C 3 alkoxy; aryl, optionally substituted with cyano, nitro, halogen, C 1 -C 3 alkyl, C 1 -C 3 alkoxy; an amino protecting group; or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein said heterocyclic ring is optionally substituted with C 1 C_1 - C 3 C_3 alkyl; and wherein the wavy line indicates the attachment to the oxygen of said OR 2 group.

8. The compound of claim 1, wherein said compound is selected from [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] , [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] , •9. An oligomer comprising at least one compound of formula (IV) [Image disponible dans le document PDF, Image available in the PDF document] (IV) wherein independently for each of said at least one compound of formula (IV) one of T 3 or T 4 is a nucleosidic linkage group; the other of T 3 and T 4 is OR 1 , OR 2 , a 5' terminal group, a 7' terminal group or a nucleosidic linkage group, wherein R 1 is H or a hydroxyl protecting group, and R 2 is a phosphorus moiety of the formula (VII): [Image disponible dans le document PDF, Image available in the PDF document] wherein: W represents O, S or Se or W represents an electron pair; R 3 and R 4 are independently of each other H, halogen, OH, OR 5 , NR 6 R 7 , SH, SR 8 , C 1 - C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 aminoalkyl; wherein R 5 is C 1 -C 9 alkyl, optionally substituted with cyano, nitro, halogen, - NHC(O)C 1 -C 3 alkyl, -NHC(O)C 1 -C 3 haloalkyl, C 1 -C 3 alkylsulfonyl; aryl, C 1 - C 6 alkylenearyl, C 1 -C 6 alkylenediaryl, each independently of each other optionally substituted with cyano, nitro, halogen, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 C_1 - C 4 C_4 haloalkoxy, N H C ( O ) C 1 − C 3 NHC(O)C_1-C_3 alkyl, N H C ( O ) C 1 − C 3 NHC(O)C_1-C_3 haloalkyl, C 1 C_{1} C 3 alkylsulfonyl; acetyl; a hydroxyl protecting group; R 6 and R 7 are independently of each other hydrogen, C 1 -C 9 alkyl optionally substituted with cyano, nitro, halogen, C 2 -C 6 alkenyl, C 3 -C 6 cycloalkyl, C 1 -C 3 alkoxy; aryl optionally substituted with cyano, nitro, halogen, C 1 -C 3 alkyl, C 1 -C 3 alkoxy; an amino protecting group; or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein said heterocyclic ring is optionally substituted with C 1 C_1 - C 3 C_3 alkyl; R 8 is a thiol protecting group; and wherein the wavy line indicates the attachment to the oxygen of said OR 2 group; Bx is selected from a purine base or pyrimidine base; wherein each nucleosidic linkage group is independently of each other selected from a phosphodiester linkage group, a phosphotriester linkage group, a phosphorothioate linkage group, a phosphorodithioate linkage group, a phosphonate linkage group, a phosphonothioate linkage group, a phosphinate linkage group, a phosphorthioamidate linkage or a phosphoramidate linkage group; and wherein each terminal group is independently of each other selected from a capping group, a diphosphate, a triphosphate, a label, a dye, a reporter group, a solid support, a non-nucleosidic group, an antibody, or a conjugate group.

10. The oligomer of claim 9, wherein said label is a fluorescent label.

11. The oligomer of claim 10, wherein said fluorescent label is fluorescein or rhodamine.

12. The oligomer of any one of claims 9 to 11, wherein Bx is selected from uracil, thymine, cytosine, 5-methylcytosine, adenine or guanine.

13. The oligomer of any one of claims claim 9 to 12, wherein said compound of formula (IV) is a compound of formula (V): [Image disponible dans le document PDF, Image available in the PDF document] V) wherein (i) T 3 is a nucleosidic linkage group, and T 4 is a 7' terminal group, OR 1 , or OR 2 ; or (ii) T 3 T_3 is a 5' terminal group, O R 1 OR_1 , or O R 2 OR_2 ; and T 4 is a nucleosidic linkage group; or (iii) T 3 and T 4 are independently of each other a nucleosidic linkage group.

14. The oligomer of claim 13, wherein: (i) T 3 is a nucleosidic linkage group, and T 4 is a 7' terminal group or OR 1 ; or (ii) T 3 T_3 is a 5' terminal group or O R 2 OR_2 ; and T 4 is a nucleosidic linkage group; or (iii) T 3 and T 4 are independently of each other a nucleosidic linkage group.

15. The oligomer of any one of the claims 9 to 12, wherein said compound of formula (IV) is a compound of formula (VI): [Image disponible dans le document PDF, Image available in the PDF document] VI) wherein (i) T 3 is a nucleosidic linkage group, and T 4 is a 7' terminal group, OR 1 , or OR 2 ; or (ii) T 3 T_3 is a 5' terminal group, O R 1 OR_1 , or O R 2 OR_2 ; and T 4 is a nucleosidic linkage group; or (iii) T 3 and T 4 are independently of each other a nucleosidic linkage group.

16. The oligomer of claim 15, wherein: (i) T 3 is a nucleosidic linkage group, and T 4 is a 7' terminal group or OR 2 ; or (ii) T 3 T_3 is a 5' terminal group or O R 1 OR_1 ; and T 4 is a nucleosidic linkage group; or (iii) T 3 and T 4 are independently of each other a nucleosidic linkage group.

17. The oligomer of any one of claims 9 to 16, wherein each nucleosidic linkage group is independently of each other selected from a phosphodiester linkage group or a phosphorothioate linkage group.

18. The oligomer of claim 17, wherein each nucleosidic linkage group is a phosphorothicate linkage group.

19. The oligomer of claim 17, wherein each nucleosidic linkage group is a phosphodiester linkage group.

20. The oligomer of any one of claims 9 to 19 comprising at least two contiguous compounds of formula (IV), wherein each of the contiguous compounds of formula (IV) is independently linked to the adjacent contiguous compound of formula (IV) by the nucleosidic linkage group, wherein the nucleosidic linkage group links a 5' terminus and a 7' terminus of two contiguous compounds of formula (IV).

21. The oligomer of claim 20, wherein said oligomer consists of at least two contiguous compounds of formula (IV), wherein each of the contiguous compounds of formula (IV) is independently linked to the adjacent contiguous compound of formula (IV) by the nucleosidic linkage group, wherein the nucleosidic linkage group links a 5' terminus and a 7' terminus of two contiguous compounds of formula (IV).

22. The oligomer of any one of claims 9 to 18, wherein said oligomer comprises at least one nucleic acid sequence, wherein said nucleic acid sequence comprises said at least one compound of formula (IV), and wherein said nucleic acid sequence is selected from any one of the SEQ ID NO: 1 to 24.

23. The oligomer of claim 22, wherein said oligomer consists of at least one nucleic acid sequence, wherein said nucleic acid sequence comprises said at least one compound of formula (IV), and wherein said nucleic acid sequence is selected from any one of the SEQ ID NO: 1 to 24.

24. The oligomer of claim 22 or 23, wherein said nucleic acid sequence is SEQ ID NO: 24.

25. The oligomer of any one of claims 13-14, wherein the oligomer comprises a nucleic acid sequence, wherein said nucleic acid sequence consists of at least two contiguous compounds of formula (V), wherein said nucleic acid sequence is flanked on its 5' terminus and on its 7' terminus by at least one nucleotide or nucleoside that is different from the compound of formula (V), wherein the 5' terminus of said nucleic acid sequence is linked to a 5' terminus of the nucleotide or nucleoside that is different from the compound of formula (V), and wherein the 7' terminus of said nucleic acid sequence is linked to a 3' terminus of the nucleotide or nucleoside that is different from the compound of formulae (V).

26. The oligomer of claim 25, wherein each nucleosidic linkage group is independently of each other selected from a phosphodiester linkage group or a phosphorothioate linkage group.

27. The oligomer of claim 25, wherein each nucleosidic linkage group is a phosphorothioate linkage group.

28. The oligomer of claim 25, wherein each nucleosidic linkage group is a phosphodiester linkage group.

29. The oligomer of any one of claims 25 to 28, wherein said oligomer comprises at least one nucleic acid sequence, wherein said nucleic acid sequence comprises said at least one compound of formula (V), and wherein said nucleic acid sequence is selected from any one of SEQ ID NO: 1 to 24.

30. The oligomer of claim 29, wherein said oligomer consists of at least one nucleic acid sequence, wherein said nucleic acid sequence comprises said at least one compound of formula (V), and wherein said nucleic acid sequence is selected from any one of SEQ ID NO: 1 to 24.

31. The oligomer of claim 29 or 30, wherein said nucleic acid sequence is SEQ ID NO: 24.

32. The oligomer of any one of claims 15-16, wherein the oligomer comprises a nucleic acid sequence, wherein said nucleic acid sequence consists of at least two contiguous compounds of formula (VI), wherein said nucleic acid sequence is flanked on its 5' terminus and on its 7' terminus each by at least one nucleotide or nucleoside that is different from the compound of formula (VI), wherein the 5' terminus of said nucleic acid sequence is linked to a 3' terminus of the nucleotide or nucleoside that is different from the compound of formula (VI), and wherein the 7' terminus of said nucleic acid sequence is linked to a 5' terminus of the nucleotide or nucleoside that is different from the compound of formula (VI).

33. The oligomer of claim 32, wherein each nucleosidic linkage group is independently of each other selected from a phosphodiester linkage group or a phosphorothioate linkage group.

34. The oligomer of claim 32, wherein each nucleosidic linkage group is a phosphorothioate linkage group.

35. The oligomer of claim 32, wherein each nucleosidic linkage group is a phosphodiester linkage group.

36. The oligomer of any one of claims 32 to 35, wherein said oligomer comprises at least one nucleic acid sequence, wherein said nucleic acid sequence comprises said at least one compound of formula (V), and wherein said nucleic acid sequence is selected from any one of SEQ ID NO: 1 to 24.

37. The oligomer of claim 36, wherein said oligomer consists of at least one nucleic acid sequence, wherein said nucleic acid sequence comprises said at least one compound of formula (V), and wherein said nucleic acid sequence is selected from any one of SEQ ID NO: 1 to 24.

38. The oligomer of claim 36 or 37, wherein said nucleic acid sequence is SEQ ID NO: 24.

39. The oligomer of any one of claims 9 to 12, wherein said compound of formula (IV) is selected from [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] , [Image disponible dans le document PDF, Image available in the PDF document]40. The oligomer of claim 39, wherein each nucleosidic linkage group is independently of each other selected from a phosphodiester linkage group or a phosphorothioate linkage group.

41. The oligomer of claim 39, wherein each nucleosidic linkage group is a phosphorothioate linkage group.

42. The oligomer of claim 39, wherein each nucleosidic linkage group is a phosphodiester linkage group.

43. The oligomer of any one of claims 39 to 42, wherein said oligomer comprises at least one nucleic acid sequence, wherein said nucleic acid sequence comprises said at least one compound of formula (V), and wherein said nucleic acid sequence is selected from any one of SEQ ID NO: 1 to 24.

44. The oligomer of claim 43, wherein said oligomer consists of at least one nucleic acid sequence, wherein said nucleic acid sequence comprises said at least one compound of formula (V), and wherein said nucleic acid sequence is selected from any one of SEQ ID NO: 1 to 24.

45. The oligomer of claim 43 or 44, wherein said nucleic acid sequence is SEQ ID NO: 24.

46. The oligomer of any one of claims 9 to 45 for use as a medicament in the prevention, treatment or diagnosis of a disease.

47. The oligomer of claim 46, wherein said disease is a muscular dystrophy.

48. The oligomer of claim 47, wherein said muscular dystrophy is Duchenne muscular dystrophy.

49. Use of an oligomer of any one of claims 9 to 45 in the manufacture of a medicament for the prevention, treatment or diagnosis of a disease.

50. The use of claim 49, wherein said disease is a muscular dystrophy.

51. The use of claim 50, wherein said muscular dystrophy is Duchenne muscular dystrophy.

52. Use of an oligomer of any one of claims 9 to 45 for the prevention, treatment or diagnosis of a disease.

53. The use of claim 52, wherein said disease is a muscular dystrophy.

54. The use of claim 53, wherein said muscular dystrophy is Duchenne muscular dystrophy.