Acyl derivatives of 16-membered macrolides. I. Synthesis and biological properties of 3"-O-propionylleucomycin A5 (TMS-19-Q).
Using leucomycin A5 (1), 3"-O-propionylleucomycin A5 (7) was synthesized by the following synthetic route: 2"-O-acetylation, 3,9-di-O-trimethylsilylation, 3"-O-propionylation, 3,9-di-O-detrimethylsilylation and 2'-O-deacetylation. Acylation of the 3"-tertiary hydroxyl group of 2'-O-acetyl-3,9-di-O-trimethylsilylleucomycin A5 with propionyl chloride in the presence of tribenzylamine at 70 degrees C gave a 3"-O-propionyl 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.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D001419:Bacteria / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D004285:Dogs; D007933:Leucomycins / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D051379:Mice; D015644:Miocamycin / Q000031:analogs & derivatives*; D051381:Rats
D000900:Anti-Bacterial Agents; D007933:Leucomycins; D015644:Miocamycin; C033383:rokitamycin