A Formal Synthesis of Ezetimibe via Cycloaddition/Rearrangement Cascade Reaction

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• 作者：Micha艂 Michalak ; Maciej Stodulski ; Sebastian Stecko ; Adam Mames ; Irma Panfil ; Magdalena Soluch ; Bart艂omiej Furman ; Marek Chmielewski
• 刊名：Journal of Organic Chemistry
• 出版年：2011
• 出版时间：August 19, 2011
• 年：2011
• 卷：76
• 期：16
• 页码：6931-6936
• 全文大小：830K
• 年卷期：v.76,no.16(August 19, 2011)
• ISSN：1520-6904

文摘

A formal synthesis of a powerful cholesterol inhibitor, ezetymibe 1, is described. The crucial step of the synthesis is based on Cu(I)-mediated Kinugasa cycloaddition/rearrangement cascade reaction between terminal acetylene derived from acetonide of l-glyceraldehyde and suitable C,N-diarylnitrone. The adduct with (3R,4S) configuration at the azetidinone ring, obtained with high stereoselectivity, was subsequently subjected to deprotection of the diol side chain followed by glycolic cleavage and base-induced isomerization at the C3 carbon atom to afford the (3S,4S) aldehyde, which has been already transformed into ezetimibe by the Schering鈥揚lough group.