Modifications of a macrolide antibiotic midecamycin (SF-837). I. Synthesis and structure of 9,3''-diacetylmidecamycin.
9,3''-Diacetylmidecamycin (12) was synthesized from 4''-depropionyl-9,2',4''-triacetylmidecamycin (8) by heating the latter with propionic anhydride in pyridine followed by removal of 2'-acetyl group, with or without 18-enolpropionyl group. Direct acetylation of midecamycin (1) led to the formation of the 3'',4''-positional isomer (6). The structure of 12 was determined by mass, NMR and chemical degradation. The location of 3''-acetyl group was shown by the stereospecific 3 leads to 1 acetyl migration catalyzed by a base of 3-O-acetyl-4-O-propionyl-L-mycarose (13), and comparison of NMR and mass fragmentation with the 3,4-positional isomer (15). The latter's structure was independently supported by the nuclear Overhauser effect between methyl and propionyl group at C-3. The intramolecular 4 leads to 3 acyl shift that was taken place in the forced acylation of the mycarose moiety was found to be affected by the anomeric configuration, nature of aglycones and reaction temperature. Reverse 3 leads to 4 acyl migration occurred in acidic hydrolysis.
D000107:Acetylation; D000900:Anti-Bacterial Agents / Q000031:analogs & derivatives; D055598:Chemical Phenomena; D002621:Chemistry; D006868:Hydrolysis; D007933:Leucomycins / Q000031:analogs & derivatives / Q000032:analysis / Q000138:chemical synthesis
D000900:Anti-Bacterial Agents; D007933:Leucomycins