MODIFICATIONS OF A MACROLIDE ANTIBIOTIC MIDECAMYCIN (SF-837) .1. SYNTHESIS AND STRUCTURE OF 9,3''-DIACETYLMIDECAMYCIN

9,3"-Diacetylmidecamycin (12) was synthesized from 4"-depropionyl-9,2'',4"-triacetylmidecamycin 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 led to the formation of the 3'',4"-positional isomer. The structure of 12 was determined by mass, NMR and chemical degradation. The location of 3"-acetyl group was shown by the stereospecific 3 .fwdarw. 1 acetyl migration catalyzed by a base of 3-O-acetyl-4-O-propionyl-L-mycarose and comparison of NMR and mass fragmentation with the 3,4-positional isomer. The latter''s structure was independently supported by the nuclear Overhauser effect between methyl and propionyl group at C-3. The intramolecular 4 .fwdarw. 3 acyl shift that was taken place in the forced acylation of the mycarose moiety was affected by the anomeric configuration, nature of aglycones and reaction temperature. Reverse 3 .fwdarw. 4 acyl migration occurred in acidic hydrolysis.