A Formal Synthesis of Ezetimibe via Cycloaddition/Rearrangement Cascade Reaction

被引：35

作者：

Michalak, Michal ^{[1
]}

Stodulski, Maciej ^{[1
]}

Stecko, Sebastian ^{[1
]}

Mames, Adam ^{[1
]}

Panfil, Irma ^{[1
]}

Soluch, Magdalena ^{[1
]}

Furman, Bartlomiej ^{[1
]}

Chmielewski, Marek ^{[1
]}

机构：

[1] Polish Acad Sci, Inst Organ Chem, PL-01224 Warsaw, Poland

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2011年 / 76卷 / 16期

关键词：

BETA-LACTAMS; ENANTIOSELECTIVE SYNTHESIS; CHOLESTEROL; NITRONES; CYCLOADDITION; CARBAPENAMS; INHIBITOR; ALKYNES;

D O I：

10.1021/jo2010846

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

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-Plough group.

引用

页码：6931 / 6936

页数：6

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