A Practical Synthesis of the Ansa Chain of Benzenic Ansamycin Antibiotics: Total Synthesis of an Ansatrienol Derivative

Abstract

A practical and stereocontrolled synthetic approach towards the ansa chain of the benzenic ansamycins (mycotrienins) is described, which can be scaled up to multigram quantities. Key features of the synthesis are the formation of the Z-configured tri­substituted double bond by a one-pot esterification of allyl(diisopropoxy)borane and ring-closing metathesis, formation of the β-keto ester via ethyl diazoacetate addition to an aldehyde, and use of the Duthaler-Hafner acetate aldol reaction for the introduction of the stereocenter at C3. The practicality of this synthesis is demonstrated by the preparation of an ansatrienol derivative, representing­ a formal total synthesis of the ansatrienins.