A1,3-strain enabled retention of chirality during bis-cyclization of β-ketoamides: total synthesis of (?)-salinosporamide A and (?)-homosalinosporamide A?

Chemical Communications Pub Date: 2010-05-25 DOI: 10.1039/C0CC00607F

Abstract

A concise, enantioselective synthesis of the Phase I anticancer agent, (?)-salinosporamide A, is described. The brevity of the described strategy stems from a key bis-cyclization of a β-keto tertiary amide, accomplished on gram scale, which retains optical purity enabled by A1,3-strain rendering epimerization slow relative to the rate of bis-cyclization. The versatility of the strategy for derivative synthesis is demonstrated by the synthesis of (?)-homosalinosporamide A.

Graphical abstract: A1,3-strain enabled retention of chirality during bis-cyclization of β-ketoamides: total synthesis of (?)-salinosporamide A and (?)-homosalinosporamide A
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