Chemoselective synthesis of erythromycin A ketolides substituted in the C10-methyl group.
The substrate for selective substitution in the C10-methyl group in erythromycin A derivatives was 10,11-anhydro-6O-methyl-descladinosylerythromycin. The latter, as an N-oxide, was reacted with NBS in acetic acid to form an allylic acetate. Nucleophilic substitutions and carbylation by Pd-catalysed cross-coupling reactions provided products substituted in the C10-methyl group. Methods for the preparation of 10-methylene derivatives of 11N,12O-cyclocarbamate 3-ketolides are described. The methylene group is part of an alpha,beta-unsaturated carbonyl system involving the 9-keto group. The products from conjugated addition are substituted in the C10-methyl group.
Gunnes
Sølvi
S
Department of Chemistry, University of Oslo, N-0315 Oslo, Norway.
Undheim
Kjell
K
D004917:Erythromycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D048628:Ketolides / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D013237:Stereoisomerism
D048628:Ketolides; D004917:Erythromycin