A Synthesis of a Spirocyclic Macrocyclic Protease Inhibitor for the Treatment of Hepatitis C

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• 作者：Cheol K. Chung ; Ed Cleator ; Aaron M. Dumas ; Jacqueline D. Hicks ; Guy R. Humphrey ; Peter E. Maligres ; Andrew F. Nolting ; Nelo Rivera ; Rebecca T. Ruck ; Michael Shevlin
• 刊名：Organic Letters
• 出版年：2016
• 出版时间：March 18, 2016
• 年：2016
• 卷：18
• 期：6
• 页码：1394-1397
• 全文大小：323K
• ISSN：1523-7052

文摘

The development of a convergent and highly stereoselective synthesis of an HCV NS3/4a protease inhibitor possessing a unique spirocyclic and macrocyclic architecture is described. A late-stage spirocyclization strategy both enabled rapid structure–activity relationship studies in the drug discovery phase and simultaneously served as the basis for the large scale drug candidate preparation for clinical use. Also reported is the discovery of a novel InCl₃-catalyzed carbonyl reduction with household aluminum foil or zinc powder as the terminal reductant.