TOTAL SYNTHESIS OF THE MACROLIDE ANTIBIOTIC RUTAMYCIN-B

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 and alkylation reactions to control the absolute stereochemical relationships. The polypropionate fragment was assembled from its C1-C-8 and C-9-C17 subunits, which were joined through a diastereoselective, mismatched, double-stereodifferentiating 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.