Synthesis of [4,5-bis(hydroxymethyl)-1,3-oxathiolan-2-yl]nucleosides as potential inhibitors of HIV via stereospecific base-induced rearrangement of a 2,3-epoxy thioacetate

被引：25

作者：

Branalt, J

Kvarnstrom, I

Classon, B

Samuelsson, B

机构：

[1] LINKOPING UNIV, DEPT CHEM, S-58183 LINKOPING, SWEDEN

[2] UNIV STOCKHOLM, ARRHENIUS LAB, DEPT ORGAN CHEM, S-10691 STOCKHOLM, SWEDEN

[3] AB HASSLE, S-43183 MOLNDAL, SWEDEN

来源：

JOURNAL OF ORGANIC CHEMISTRY | 1996年 / 61卷 / 11期

关键词：

D O I：

10.1021/jo960009c

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The synthesis of [4,5-bis(hydroxymethyl)-1,3-oxathiolan-2-yl]nucleosides is described. 2,3-Epoxy alcohol 10 was converted in one pot into thioacetate 11. Treatment of 11 under mild alkaline conditions gave thiirane 12 with inversion of configuration at C-2. We also found that thioacetate 11 rearranges into thiirane 14 under mild acidic conditions. This rearrangement reaction was shown by independent synthesis to proceed with net retention of configuration at C-2. We have proposed a tentative mechanism which may explain the results obtained. Opening of thiiranes 12; and 14 followed by deprotection gave (2R,3R)-2-thiothreitol (23) and (2S,3R)-2-thioerythritol (25), respectively. Regioselective silylation of the primary hydroxyl groups of 23 followed by treatment with trimethyl orthoformate gave 2-methoxy-1,3-oxathiolanes 26 and 27. Condensation with silylated baser followed by deprotection and separation of the anomers gave the oxathiolanyl-nucleosides. Compounds 29-31, 34, and 35 were found to be inactive when tested for inhibition of HIV-1 activity in vitro.

引用

页码：3604 / 3610

页数：7

共 17 条

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