STEREOCONTROLLED SYNTHESIS OF C-2-SYMMETRICAL AND PSEUDO-C-2-SYMMETRICAL DIAMINO ALCOHOLS AND DIOLS FOR USE IN HIV PROTEASE INHIBITORS

被引：89

作者：

KEMPF, DJ ^{[1
]}

SOWIN, TJ ^{[1
]}

DOHERTY, EM ^{[1
]}

HANNICK, SM ^{[1
]}

CODAVOCI, L ^{[1
]}

HENRY, RF ^{[1
]}

GREEN, BE ^{[1
]}

SPANTON, SG ^{[1
]}

NORBECK, DW ^{[1
]}

机构：

[1] ABBOTT LABS,DEPT STRUCT CHEM,ABBOTT PK,IL 60064

来源：

JOURNAL OF ORGANIC CHEMISTRY | 1992年 / 57卷 / 21期

关键词：

D O I：

10.1021/jo00047a023

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The stereocontrolled syntheses of dibenzyldiamino alcohol 1 and dibenzyldiamino diols 2-4, core units of potent C2-symmetric and pseudo-C2-symmetric inhibitors of HIV protease, are described, starting from phenylalanine. Stereoselective epoxidation of trans olefin 7, produced by S(N)2' displacement of an allylic mesylate, followed by regiospecific epoxide opening with lithium azide provided the azido alcohol 8 as the major product. Azide reduction and deprotection led to diamine 1. Protected diamino diols 15-17 were prepared expeditiously by intermolecular titanium- or vanadium-mediated pinacol coupling of protected phenylalaninal. Methods for the stereospecific interconversion of the major (3R,4R,5R,6S) isomer to the desired (3S,4R,5S,6S) isomer via intramolecular hydroxyl inversion are described.

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页码：5692 / 5700

页数：9

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