Asymmetric Synthesis of cis-2,5-Disubstituted Pyrrolidine, the Core Scaffold of 尾3-AR Agonists

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• 作者：Feng Xu ; John Y. L. Chung ; Jeffery C. Moore ; Zhuqing Liu ; Naoki Yoshikawa ; R. Scott Hoerrner ; Jaemoon Lee ; Maksim Royzen ; Ed Cleator ; Andrew G. Gibson ; Robert Dunn ; Kevin M. Maloney ; Mahbub Alam ; Adrian Goodyear ; Joseph Lynch ; Nobuyashi Yasuda ; Paul N. Devine
• 刊名：Organic Letters
• 出版年：2013
• 出版时间：March 15, 2013
• 年：2013
• 卷：15
• 期：6
• 页码：1342-1345
• 全文大小：276K
• 年卷期：v.15,no.6(March 15, 2013)
• ISSN：1523-7052

文摘

A practical, enantioselective synthesis of cis-2,5-disubstituted pyrrolidine is described. Application of an enzymatic DKR reduction of a keto ester, which is easily accessed through a novel intramolecular N鈫扖 benzoyl migration, yields syn-1,2-amino alcohol in >99% ee and >99:1 dr. Subsequent hydrogenation of cyclic imine affords the cis-pyrrolidine in high diastereoselectivity. By integrating biotechnology into organic synthesis and isolating only three intermediates over 11 steps, the core scaffold of 尾₃-AR agonists is synthesized in 38% overall yield.