A Stereoselective Synthesis of the Macrolide Core of Migrastatin [1]

Abstract

A concise and efficient synthesis of the macrolide core of migrastatin, an antimetastatic agent, is reported. In this synthetic protocol, the key intermediate (4R,5S,6S)-6-methoxy-5-(4-meth­oxy­benzyloxy)-2,4-dimethylocta-2,7-dien-1-ol is obtained after dia­stereoselective aldol condensation, Lewis acid mediated diastereoselective addition, and an exclusive Z-olefination sequence have been employed. Yamaguchi esterification of the key intermediate, followed by ring-closing metathesis produced the desired macrolide in high selectivity and good yield.

Key words

metastasis - macrolide - Evans aldol condensation - Wittig olefination - ring-closing metathesis

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DRL Publication No. 652.

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DRL Publication No. 652.