Synthetic studies in the lysocellin family of polyether antibiotics. The total synthesis of ferensimycin B

• Published in: Journal of the American Chemical Society Vol. 113; no. 20; pp. 7613 - 7630
• Main Authors: Evans, David A, Polniaszek, Richard P, DeVries, Keith M, Guinn, Denise E, Mathre, David J
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.09.1991; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Multidisciplinary; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; X-537A; EPOXIDES; ALDOL CONDENSATIONS; ASYMMETRIC-SYNTHESIS; ACID; ALKYLATIONS; LASALOCID-A; SYNTHON; EPIMERS; Antibiotic; Five membered ring; Asymmetric synthesis; Carboxylic acid; Six membered ring; Ketol; Oxygen heterocycle; Total synthesis
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja00020a025

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.