Chemistry of amphotericin B. Degradation studies and preparation of amphoteronolide B

• Published in: Journal of the American Chemical Society Vol. 110; no. 14; pp. 4660 - 4672
• Main Authors: Nicolaou, K. C, Chakraborty, T. K, Ogawa, Y, Daines, R. A, Simpkins, N. S, Furst, G. T
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.07.1988; 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; Conjugated polyenic compound; COSY sequence; Aglycone; Oxygen heterocycle; Circular dichroism; Macrocycle; Two dimension spectrometry; Bicyclic compound; Chemical decomposition; Glycoside; Polyol; NMR spectrum; Protection
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja00222a027

Amphotericin B (1) was converted to a series of protected derivatives (3-5, 27). Compound 5 was degraded by ozonolysis and further elaborated to fragments 8, 14, and 15, three potential intermediates in a projected total systhesis of amphotericin B (1). A novel oxidative deglycosidation procedure based on radical bromination was devised and applied to the degradation of 5 and 27 to heptaenones 21 and 28, respectively. These heptaenones were stereospecifically reduced with sodium borohydride to amphoteronolide B derivates 23 and 29, respectively. The R stereochemistry of the C-19 hydroxyl group arising from the reduction of these polyeones was confirmed by using Nakanishi''s CD method on derivative 26 obtained by appropriate chemical manipulations of the reduction products. The aglycon of amphotericin B, amphoteronolide B (2), was obtained from 29 by desilylation followed by methyl ester hydrolysis.