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.

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