Synthesis of the HCV Protease Inhibitor Vaniprevir (MK-7009) Using Ring-Closing Metathesis Strategy

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• 作者：Jongrock Kong ; Cheng-yi Chen ; Jaume Balsells-Padros ; Yang Cao ; Robert F. Dunn ; Sarah J. Dolman ; Jacob Janey ; Hongmei Li ; Michael J. Zacuto
• 刊名：The Journal of Organic Chemistry
• 出版年：2012
• 出版时间：April 20, 2012
• 年：2012
• 卷：77
• 期：8
• 页码：3820-3828
• 全文大小：539K
• 年卷期：v.77,no.8(April 20, 2012)
• ISSN：1520-6904

文摘

A highly efficient synthesis of Vaniprevir (MK-7009) has been accomplished in nine linear steps and 55% overall yield. The key features of this synthesis include a cost-effective synthesis of the isoindoline subunit and efficient construction of the 20-membered macrocyclic core of Vaniprevir (MK-7009) utilizing ring-closing metathesis technology. A high-performing ring-closing metathesis protocol has been achieved by simultaneous slow addition of the ruthenium catalyst (0.2 mol %) and the diene substrate at a concentration of 0.13 M.