Synthesis of a Long Acting HIV Protease Inhibitor via Metal or Enzymatic Reduction of the Appropriate Chloro Ketone and Selective Zinc Enolate Condensation with an Amino Epoxide

被引：5

作者：

Houpis, Ioannis N. ^{[1
]}

Liu, Renmao ^{[2
]}

Liu, Lin ^{[2
]}

Wang, Yanfei ^{[2
]}

Dong, Nengfa ^{[2
]}

Zhao, Xiangan ^{[2
]}

Zhang, Yan ^{[2
]}

Xiao, Tingting ^{[2
]}

Wang, Youchu ^{[2
]}

Depre, Dominique ^{[2
]}

Nettekoven, Ulrike ^{[3
]}

Vogel, Michael ^{[4
]}

Wilson, Rob ^{[4
]}

Collier, Steve ^{[4
]}

机构：

[1] Janssen Pharmaceut, API Development, B-2340 Beerse, Belgium

[2] STA Pharmaceut, Shanghai 200131, Peoples R China

[3] Solvias AG, CH-4303 Kaiseraugst, Switzerland

[4] Codexis, Redwood City, CA 94063 USA

来源：

ADVANCED SYNTHESIS & CATALYSIS | 2013年 / 355卷 / 09期

关键词：

asymmetric ketone reduction; enzymatic ketone reduction; long acting HIV protease inhibitors; zinc enolate addition to epoxides; ALPHA-CHLOROKETONES; POTENT; ISOSTERES; DESIGN;

D O I：

10.1002/adsc.201300074

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

This paper describes a new convergent approach to the synthesis of an HIV protease inhibitor which was designed to be suitable in long acting formulations. Unique features in the synthesis include an asymmetric hydrogenation as well as enzymatic reduction of a key chloro ketone intermediate, to set the threo stereochemistry in the corresponding epoxide and the diastereoselective coupling of the latter with the zinc enolate of a suitable functionalized amide derivative.

引用

页码：1829 / 1839

页数：11

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