THE AUTOMATED SYNTHESIS OF SULFUR-CONTAINING OLIGODEOXYRIBONUCLEOTIDES USING 3H-1,2-BENZODITHIOL-3-ONE 1,1-DIOXIDE AS A SULFUR-TRANSFER REAGENT

被引：256

作者：

IYER, RP ^{[1
]}

PHILLIPS, LR ^{[1
]}

EGAN, W ^{[1
]}

REGAN, JB ^{[1
]}

BEAUCAGE, SL ^{[1
]}

机构：

[1] US FDA,CTR BIOL EVALUAT & RES,DIV BIOCHEM & BIOPHYS,8800 ROCKVILLE PIKE,BETHESDA,MD 20892

来源：

JOURNAL OF ORGANIC CHEMISTRY | 1990年 / 55卷 / 15期

关键词：

D O I：

10.1021/jo00302a039

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Several polysulfides were tested as potential sulfur-transfer reagents during the automated synthesis of oligodeoxyribonucleoside phosphorothioates via the “deoxyribonucleoside phosphoramidite” approach. The thiosulfonate 3H-l,2-benzodithiol-3-one 1,1-dioxide (12) was particularly efficient as a sulfurizing reagent. A 0.2 M solution of 12 in acetonitrile converted the dinucleoside monophosphite triesters 13a-d into the corresponding phosphorothioates 15a-d within 30 s in near quantitative yields. This reagent led to rapid, efficient (stepwise yields of 99%), and reliable automated synthesis of phosphorothioate oligomers (28-mers) complementary to the mRNA of the HIV-1 rev gene, carrying either exclusively or a predetermined number of P(S) linkages. Additionally, oligomers exposed to prolonged treatment (24 h) with the sulfurizing reagent did not show any detectable modification of the nucleosidic bases. © 1990, American Chemical Society. All rights reserved.

引用

页码：4693 / 4699

页数：7

共 40 条

[11] NUCLEOSIDE H-PHOSPHONATES - VALUABLE INTERMEDIATES IN THE SYNTHESIS OF DEOXYOLIGONUCLEOTIDES [J].

FROEHLER, BC ;

MATTEUCCI, MD .

TETRAHEDRON LETTERS, 1986, 27 (04) :469-472

[12] SYNTHESIS OF DNA VIA DEOXYNUCLEOSIDE H-PHOSPHONATE INTERMEDIATES [J].

FROEHLER, BC ;

NG, PG ;

MATTEUCCI, MD .

NUCLEIC ACIDS RESEARCH, 1986, 14 (13) :5399-5407

[13]

GAREGG PJ, 1985, CHEM SCRIPTA, V25, P280

[14] NUCLEOSIDE H-PHOSPHONATES .3. CHEMICAL SYNTHESIS OF OLIGODEOXYRIBONUCLEOTIDES BY THE HYDROGENPHOSPHONATE APPROACH [J].

GAREGG, PJ ;

LINDH, I ;

REGBERG, T ;

STAWINSKI, J ;

STROMBERG, R ;

HENRICHSON, C .

TETRAHEDRON LETTERS, 1986, 27 (34) :4051-4054

[15] ORGANIC SULPHUR CHEMISTRY .9. CHEMISTRY OF THIOLSULFONATES AND RELATED DERIVATIVES - NUCLEOPHILIC REACTIONS ON SULFENYL SULFUR [J].

HARPP, DN ;

GLEASON, JG ;

ASH, DK .

JOURNAL OF ORGANIC CHEMISTRY, 1971, 36 (02) :322-&

[16]

HORTMANN AG, 1978, J ORG CHEM, V43, P3374

[17] 3H-1,2-BENZODITHIOLE-3-ONE 1,1-DIOXIDE AS AN IMPROVED SULFURIZING REAGENT IN THE SOLID-PHASE SYNTHESIS OF OLIGODEOXYRIBONUCLEOSIDE PHOSPHOROTHIOATES [J].

IYER, RP ;

EGAN, W ;

REGAN, JB ;

BEAUCAGE, SL .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1990, 112 (03) :1253-1254

[18] SYNTHESIS OF THYMIDINE OLIGONUCLEOTIDES BY PHOSPHITE TRIESTER INTERMEDIATES [J].

LETSINGER, RL ;

LUNSFORD, WB .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1976, 98 (12) :3655-3661

[19]

LIEBHABER SA, 1984, J BIOL CHEM, V259, P5597

[20]

LINKOVA MG, 1984, IAN SSSR KH, P617

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