MNBA-Mediated 尾-Lactone Formation: Mechanistic Studies and Application for the Asymmetric Total Synthesis of Tetrahydrolipstatin

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• 作者：Isamu Shiina ; Yuma Umezaki ; Nobutaka Kuroda ; Takashi Iizumi ; Shunsuke Nagai ; Takashi Katoh
• 刊名：The Journal of Organic Chemistry
• 出版年：2012
• 出版时间：June 1, 2012
• 年：2012
• 卷：77
• 期：11
• 页码：4885-4901
• 全文大小：961K
• 年卷期：v.77,no.11(June 1, 2012)
• ISSN：1520-6904

文摘

Various 尾-lactones were prepared from 尾-hydroxycarboxylic acids by intramolecular dehydration condensation using MNBA, an effective coupling reagent, along with a nucleophilic catalyst. The transition state that provides the desired 4-membered ring model system is disclosed by density functional theory (DFT) calculations, and the structural features of the transition form are discussed. This method was successfully applied to the asymmetric total synthesis of tetrahydrolipstatin (THL), an antiobestic drug used in clinical treatment to inhibit the activity of pancreatic lipase.