Synthesis of antisense oligonucleotides: Replacement of 3H-1,2-benzodithiol-3-one 1,1-dioxide (Beaucage reagent) with phenylacetyl disulfide (PADS) as efficient sulfurization reagent: From bench to bulk manufacture of active pharmaceutical ingredient

被引：47

作者：

Cheruvallath, ZS ^{[1
]}

Carty, RL ^{[1
]}

Moore, MN ^{[1
]}

Capaldi, DC ^{[1
]}

Krotz, AH ^{[1
]}

Wheeler, PD ^{[1
]}

Turney, BJ ^{[1
]}

Craig, SR ^{[1
]}

Gaus, HJ ^{[1
]}

Scozzari, AN ^{[1
]}

Cole, DL ^{[1
]}

Ravikumar, VT ^{[1
]}

机构：

[1] ISIS Pharmaceut, Carlsbad, CA 92008 USA

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2000年 / 4卷 / 03期

关键词：

D O I：

10.1021/op990077b

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

It is demonstrated that phosphorothioate oligodeoxyribonucleotides can be synthesized on scales from 1 mu mol to 150 mmol using phenylacetyl disulfide (PADS) as an efficient and economical replacement for Beaucage reagent. A 0.2 M solution of PADS in a mixture of 3-picoline and acetonitrile (1:1 v/v) as solvent with 60-120 s contact time efficiently (>99.6%) sulfurizes phosphite triesters to phosphorothioate triester linkages. Phenylacetyl disulfide reagent is inexpensive and scaleable and is currently being used by us for the manufacture of antisense phosphorothioate oligodeoxyribonucleotide active pharmaceutical ingredients (API).

引用

页码：199 / 204

页数：6

共 45 条

[1] ADVANCES IN THE SYNTHESIS OF OLIGONUCLEOTIDES BY THE PHOSPHORAMIDITE APPROACH [J].