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A Concise One‐Pot Organo‐ and Biocatalyzed Preparation of Enantiopure Hexahydrofuro[2,3‐ b ]furan‐3‐ol: An Approach to the Synthesis of HIV Protease Inhibitors
Author(s) -
Kanemitsu Takuya,
Inoue Mizuho,
Yoshimura o,
Yoneyama Kazutoshi,
Watarai Rie,
Miyazaki Michiko,
Odanaka Yuki,
Nagata Kazuhiro,
Itoh Takashi
Publication year - 2016
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201600062
Subject(s) - enantiopure drug , chemistry , biocatalysis , darunavir , kinetic resolution , protease , thiourea , combinatorial chemistry , furan , organic chemistry , lipase , catalysis , hiv 1 protease , enantioselective synthesis , stereochemistry , human immunodeficiency virus (hiv) , enzyme , reaction mechanism , medicine , family medicine , antiretroviral therapy , viral load
A simple and efficient one‐pot synthesis of enantiopure hexahydrofuro[2,3‐ b ]furan‐3‐ol, a crucial component of HIV‐1 protease inhibitors, was developed. The one‐pot process involves an organocatalytic condensation followed by an enzymatic optical resolution. The condensation of 1,2‐dihydrofuran and glycolaldehyde was achieved using Schreiner's thiourea catalyst (1 mol‐%). A subsequent lipase‐catalyzed kinetic resolution gave the target alcohol with >99 % ee . To demonstrate the practicality of this method, Darunavir, an HIV‐1 protease inhibitor used to treat multi‐drug‐resistant HIV, was synthesized.