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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
Author(s) -
Houpis Ioannis N.,
Liu Renmao,
Liu Lin,
Wang Yanfei,
Dong Nengfa,
Zhao Xiangan,
Zhang Yan,
Xiao Tingting,
Wang Youchu,
Depre Dominique,
Nettekoven Ulrike,
Vogel Michael,
Wilson Rob,
Collier Steve
Publication year - 2013
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201300074
Subject(s) - chemistry , ketone , epoxide , amide , zinc , combinatorial chemistry , protease , enzyme , stereochemistry , selective reduction , derivative (finance) , organic chemistry , catalysis , financial economics , economics
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.