Laboratoire des Fonctions Azotées et Oxygénées Complexes de l'IRCOF, CNRS UMR 6014 & FR 3038, Université de Rouen, Mont Saint-Aignan, France.
J Org Chem. 2011 Nov 18;76(22):9429-37. doi: 10.1021/jo201683u. Epub 2011 Oct 27.
The one-pot construction of functionalized α'-methoxy-γ-pyrones is detailed. Starting from α,α'-dimethoxy-γ-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 (IC(50) 44 nM) was identified.
详细介绍了官能化α'-甲氧基-γ-吡喃酮的一锅合成法。以α,α'-二甲氧基-γ-吡喃酮为起始原料，通过烯丙基锂的区域和立体选择性去对称化反应，接着进行烯醇式缩合反应，实现了分子多样性。为了深入了解这一复杂的多步反应过程，我们进行了包括密度泛函理论计算在内的大量机理研究和有见地的实验。为了说明该方法的多功能性，对一些所制备的分子进行了抑制 NADH-氧化酶和 NADH-泛醌氧化还原酶的能力评估。在此过程中，发现了一种对 NADH-氧化酶活性具有很强抑制作用的新型抑制剂（IC50 为 44 nM）。
