Total synthesis of the macrolide antibiotic rutamycin B

Abstract

A convergent asymmetric synthesis of the macrolide antibiotic rutamycin B has been achieved through the synthesis and coupling of its spiroketal and polypropionate subunits. Both fragments were constructed utilizing auxiliary-based asymmetric aldol had alkylation reactions to control the absolute stereochemical relationships. The polypropionate fragment was assembled from its C 1 -C 8 and C 9 -C 17 subunits, which were joined through a diastereoselective, mismatched, double-stereo differentiating aldol reaction. Union of the spiroketal and polypropionate subunits was accomplished through a Suzuki coupling, providing direct access to the rutamycin seco acid, which was cyclized in high yield to the protected macrolide