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.