Synthetic Study of Tautomycin and Tautomycetin. Stereocontrolled Construction of the Dialkylmaleic Anhydride Segment

Abstract

Strategies for the synthesis of a dialkylmaleic anhydride segment of tautomycin and tautomycetin are presented. The most difficult point was the stereocontrolled construction of the tetrasubstituted olefin. The maleate-type olefin construction through dehydration proved not to be adoptable because the corresponding β-hydroxyimine or aldol precursors were extremely unstable even under neutral conditions, suffering the retro-aldol-type decomposition. The Horner-Wadsworth-Emmons reaction on the α-ketoester with an appropriate protecting group had acceptable levels of diastereoselectivity giving rise to the dialkylmaleate diester, which was further led to the segment used in the synthesis of tautomycin and tautomycetin. In such the strategy, functional group protections were important in the olefination reaction and the final anhydride formation.