Acyl derivatives of 16-membered macrolides I. Synthesis and biological properties of 3”-o-propionylleucomycin A5(TMS-19-Q)

Abstract

Using leucomycin A5 (1), 3”-O-propionylleucomycin A5(7) was synthesized by the following synthetic route: 2”-0-acetylation, 3,9-di-O-trimethylsilylation, 3”-0-propionylation, 3,9-di-O-detrimethyIsilylation and 2’-O-deacetylation. Acylation of the 3”-tertiary hydroxyl group of 2,-O-acetyl-3,9-di-O-trimethylsilylleucomycin A5with propionyl chloride in the presence of tribenzylamine at 70°C gave a 3”-Opropionyl derivative in 96% yield. The structure of the final compound, 3”-O-propionylleucomycin A5 (7) was confirmed by means of mass, 1H-NMR and 13C-NMR spectrometry and chemical degradations. 3”-O-Propionylleucomycin A5 (7) showed higher antibacterial activity in vitro and higher serum levels than its mother antibiotic. The biological properties of 7 also were compared with those of josamycin and midecamycin. © 1981, JAPAN ANTIBIOTICS RESEARCH ASSOCIATION. All rights reserved.