SYNTHETIC STUDIES IN THE LYSOCELLIN FAMILY OF POLYETHER ANTIBIOTICS - THE TOTAL SYNTHESIS OF FERENSIMYCIN-B

A convergent asymmetric synthesis of the polyether antibiotic ferensimycin B has been completed. Chiral enolate bond constructions were employed to establish seven of the 16 stereocenters of the subunits 35 and 52, which comprise the C1-C-9 and C-10-C23 portions of ferensimycin B. The stereogenic centers at C3, C4, C-9, C-10, C-16, C-17, and C18 were incorporated through internal asymmetric induction, while those at C20 and C21 were established by using asymmetric epoxidation methodology. In this transformation, a vanadium-catalyzed internal epoxidation of a bis-homoallylic alcohol was employed to relay chirality from the C-13 to the C-16 oxygen-bearing stereocenter. A final aldol addition reaction on intermediates devoid of protecting groups united the fragments 52 and 35 to provide synthetic ferensimycin B, whose absolute configuration was found to be [GRAPHICS] the same as that of the closely related ionophore lysocellin. This synthesis thus establishes the absolute configuration of ferensimycin B.