A METHOD OF SYNTHESIZING AN OLIGONUCLEOTIDE USING PHOSPHORAMIDITE CHEMISTRY

摘要

A method of synthesizing an oligonucleotide using phosphoramidite chemistry characterized in that coupling a nucleoside or a nascent oligonucleotide having a free hydroxy or thiol group and a nucleoside phosphoramidite in the presence of a coupling agent and an organic base, wherein an organic base is present with the coupling agent during the coupling reaction; and wherein the coupling agent is a 1,1-dioxo-1,2-dihydro-1A6-benzo[d]isothiazol-3-one represented by the following structural formula: wherein: p is 0 or an integer from 1 to 4; X7 is O or S; R for each occurrence is a substituent, wherein each R independently is halo, a substituted or unsubstituted aliphatic group, -NR11R12, -OR13, -OC(0)R13, -C(0)OR13, cyano, a substituted or unsubstituted aryl, a substituted or unsubstituted heterocyclyl, -CHO, -COR13, -NHCOR13, a substituted or unsubstituted aralkyl, or -SR13; or two adjacent R groups taken together with the carbon atoms to which they are attached form a six membered saturated or unsaturated ring; wherein: R11 and R12 are each, independently, -H, a substituted or unsubstituted aliphatic group, a substituted or unsubstituted ary! group, a substituted or unsubstituted aralkyi group; or together with the nitrogen to which they are attached form a heterocyclyl group; and R13 is a substituted or unsubstituted aliphatic group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted aralkyi group.