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

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• 作者：Takuya Kanemitsu ; Mizuho Inoue ; Nono Yoshimura ; Kazutoshi Yoneyama ; Rie Watarai ; Michiko Miyazaki ; Yuki Odanaka ; Kazuhiro Nagata and Takashi Itoh
• 关键词：Organocatalysis ; Enzyme catalysis ; Thioureas ; Kinetic resolution ; Inhibitors
• 刊名：European Journal of Organic Chemistry
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：2016
• 期：10
• 页码：1874-1880
• 全文大小：1018K
• ISSN：1099-0690

文摘

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.