Patent ID: 7205399
Filing Date: 2007-04-17
Classification: C07H

Abstract:
1. A method for the preparation of oligonucleotides having Formula I: wherein B is H or a nucleoside base with or without protecting groups, each R1 independently is H, OH, or a 2′-OCH3, C-allyl, O-allyl, O-alkyl, O-alkylthioalkyl, O-alkoxylalkyl, alkyl, alkylhalo, O-alkylhalo, F, NH2, ONH2, O-silylalkyl, or N-phthaloyl group, each R2 independently is O, N, S, alkyl, alkyl-halo, or alkyl-halo group, each R3 independently is O, OH, H, alkyl, alkylhalo, O-alkyl, O-alkylhalo, S, N or substituted N, each R4 independently is O, each R5 independently is O or S, each R6 independently is O, OH, S, O-alkyl, O-alkylcyano, S-alkyl, or S-alkylcyano, each R7 is present or absent, but when present independently is H, removable protecting group, inverted abasic derivative, biotin, peptide, phosphate, diphosphate, triphosphate, pyrophosphate, nucleotide, nucleoside, or oligonucleotide and wherein n is an integer from about 1 to about 1000, comprising: (a) reacting a compound having Formula II: wherein each B, R1, R2, R3, and R4 are as defined in Formula I, L is a cleavable linker, and SP is a scaffold, with a compound having formula III: wherein Q is selected from the group consisting of: and wherein Z and Y each independently are selected from the group consisting of: and where any Q, Z, or Y are optionally a nucleic acid or nucleoside, under conditions suitable for the formation of a compound having Formula IV: wherein each B, R1, R2, R3, R4, L, and SP are as defined in Formula II, and R8 is a trivalent phosphorous group having groups QZ or QY as defined in Formula III; (b) reacting the compound having Formula IV with a compound having Formula V: wherein each B, R1, R2, R3, R4, and R7 are as defined in Formula I, under conditions suitable for the formation of a compound having Formula VI: wherein each B, R1, R2, R3, R4, R6, and R7, are as defined in Formula I and L and SP are as defined in Formula II; (c) oxidizing the compound of Formula VI under conditions suitable for the formation of a compound having Formula VII: wherein each B, R1, R2, R3, R4, R5, R6, and R7, are as defined in Formula I and L and SP are as defined in Formula II; (d) blocking any reactive R2 groups of Formula II or IV which have not reacted according to (a) or (b) with protective groups that prevent further reaction at R2; (e) optionally eliminating R7 from the compound of Formula VII; wherein step (a) is performed in situ without an isolating or a purifying step; (f) optionally repeating (a), (b), (c), (d), and (e); (g) cleaving the linker molecule L of Formula VII and optionally cleaving any protective groups that are present under conditions suitable for isolating a compound having Formula I.