Nucleotide precursors, nucleotide analogs and oligomeric compounds containing the same

An oligonucleotide comprising one or more compounds of formula (II):

• wherein:
• B is a heterocyclic nucleobase;
• one of L1 and L2 is an internucleoside linking group linking the compound of formula (II) to the oligomeric compound and the other of L1 and L2 is H, a protecting group, a phosphorus moiety or an internucleoside linking group linking the compound of formula (II) to the oligomeric compound,
• Y is O, NH, NR1 or N—C(═O)—R1, wherein R1 is:
• a (C1-C20)alkyl group, optionally substituted by one or more groups selected from an halogen atom, a (C1-C6)alkyl group, a (C3-C8) cycloalkyl group, a (C3-C14) heterocycle, a (C6-C14) aryl group, a (C5-C14) heteroaryl group, —O—Z1, —N(Z1)(Z2), —S—Z1, —CN, —C(=J)-O—Z1, —O—C(=J)-Z1, —C(=J)-N(Z1)(Z2), and —N(Z1)—C(=J)-Z2, wherein
• J is O or S,
• each of Z1 and Z2 is, independently, H, a (C1-C6)alkyl group, optionally substituted by one or more groups selected from a halogen atom and a (C1-C6)alkyl group,
• a (C3-C8) cycloalkyl group, optionally substituted by one or more groups selected from a halogen atom and a (C1-C6)alkyl group,
• a group —[C(═O)]m-R2-(O—CH2—CH2)p-R3, wherein
• m is an integer meaning 0 or 1,
• p is an integer ranging from 0 to 10,
• R2 is a (C1-C20)alkylene group optionally substituted by a (C1-C6)alkyl group, —O—Z3, —N(Z3)(Z4), —S—Z3, —CN, —C(═K)—O—Z3, —O—C(═K)—Z3, —C(═K)—N(Z3)(Z4), or —N(Z3)—C(═K)—Z4, wherein
• K is O or S,
• each of Z3 and Z4 is, independently, H, a (C1-C6)alkyl group, optionally substituted by one or more groups selected from a halogen atom and a (C1-C6)alkyl group, and
• R3 is selected from the group consisting of a hydrogen atom, a (C1-C6)alkyl group, a (C1-C6)alkoxy group, a (C3-C8) cycloalkyl group, a (C3-C14) heterocycle, a (C6-C14) aryl group or a (C5-C14) heteroaryl group,
• or R3 is a cell targeting moiety,
• X1 and X2 are each, independently, a hydrogen atom, a (C1-C6)alkyl group, and
• each of Ra, Rb, Rc and Rd is, independently, H or a (C1-C6)alkyl group, or a pharmaceutically acceptable salt thereof.

A method for preparing a compound of formula (I-E) comprising the steps of:

• a) reducing the compound of formula (XI)
• wherein P1, P2 and B are as defined in the general formula (I), so as to obtain a compound of formula (XVII)
• b) transferring the compound of formula (XVII) in the presence of a sulfonylating agent (e.g., p-toluene-sulfonylchloride Ts-Cl, methanesulfonylchloride Ms-Cl), so as to obtain the compound of formula (XVIII)
• wherein Ts represents a tosyl group, and
• c) subjecting the compound of formula (XVIII) to a basic condition, so as to obtain the compound of formula (I-E)