One-Pot Regio- and Stereoselective Synthesis of 伪鈥?Methoxy-纬-pyrones: Biological Evaluation as Mitochondrial Respiratory Complex Inhibitors

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• 作者：Helena Rosso ; Micha毛l De Paolis ; Val茅rie C. Collin ; Sriloy Dey ; Sidney M. Hecht ; Cristina Prandi ; Vincent Richard ; Jacques Maddaluno
• 刊名：Journal of Organic Chemistry
• 出版年：2011
• 出版时间：November 18, 2011
• 年：2011
• 卷：76
• 期：22
• 页码：9429-9437
• 全文大小：474K
• 年卷期：v.76,no.22(November 18, 2011)
• ISSN：1520-6904

文摘

The one-pot construction of functionalized 伪鈥?methoxy-纬-pyrones is detailed. Starting from 伪,伪鈥?dimethoxy-纬-pyrone, molecular diversity is attained by a regio- and stereoselective desymmetrization using allyllithium followed by vinylogous aldol reaction. Mechanistic considerations including density functional theory calculations and insightful experiments have been gathered to shed light on this complex multistep process. To illustrate the versatility of this methodology, some of the molecules prepared were evaluated for their ability to inhibit NADH-oxidase and NADH-ubiquinone oxidoreductase. In the process, a potent new inihibitor of NADH-oxidase activity (IC₅₀ 44 nM) was identified.