MODIFICATIONS OF A MACROLIDE ANTIBIOTIC MIDECAMYCIN (SF-837)

I. SYNTHESIS AND STRUCTURE OF 9, 3"-DIACETYLMIDECAMYCIN

Abstract

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→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 erect between methyl and propionyl group at C-3.
The intramolecular 4→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→4 acyl migration occurred in acidic hydrolysis.