Preparation and antibacterial activity of cyclic 2',3'-carbamate derivatives of azithromycin.
In a study of the importance of a basic amino function in erythromycin derived antibiotics, N'-demethylazithromycin 2',3'-carbamate-11,12-carbonate has been prepared in six steps from (9E)-erythromycin A 9-oxime. Reactions with phosgene provided a cyclic carbonate from the vicinal 11,12-diol, and a cyclic 2',3'-carbamate from the vicinal dimethylamino-alcohol moiety of the desosamine sugar. Further transformations provided N,N'-di(demethyl)azithromycin 2',3'-carbamate-11,12-carbonate N-methylated at position 9a. The activity of the oxime was reduced in comparison with the parent azithromycin. Hence the N,N-dimethylamino group in the desosamine sugar is important for good antibacterial activity. The course of the phosgene reactions has been verified by an X-ray analysis.
Heggelund
Audun
A
Department of Chemistry, University of Oslo, P.O. Box 1033, Blindern, N-0313 Oslo, Norway.
Rømming
Christian
C
Undheim
Kjell
K
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017963:Azithromycin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002219:Carbamates / Q000737:chemistry*; D003500:Cyclization; D050296:Microbial Viability / Q000187:drug effects; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D002219:Carbamates; D017963:Azithromycin