Asymmetric Total Synthesis of Inthomycins A, B and C.

Herein, we report the asymmetric total syntheses of inthomycin antibiotics containing a methylene-interrupted oxazolyl-triene motif. Utilizing the alpha,beta-unsaturated aldehyde as a common intermediate, all three inthomycins A-C were divergently synthesized. The asymmetric ynone reduction provided an R-configured secondary alcohol as in the natural products with high enantioselectivity. The geometrically different triene units for each inthomycin were stereoselectively established via methyl cuprate conjugate addition, isomerization of the alpha,beta-unsaturated aldehyde intermediate, and stereoretentive cross-coupling reactions.