Synthesis and antibacterial activity of some ester, amides, and hydrazides of 3-carboxyrifamycin S. Relationship between structure and activity of ansamycins.

Esters, amides, and hydrazides of 3-carboxyrifamycin S were synthesized by oxidizing the cyanohydrin of 3-formylrifamycin SV to 3-(cyanocarbonyl)rifamycin S, followed by treatment with alcohols, amines and hydrazines. The in vitro microbiological activity of the derivatives was quite low, especially toward Gram-negative bacteria. This poor activity was not shown to be due to the inadequate inhibiting action on the bacterial DNA-dependent RNA polymerase but to the poor penetration of the compounds through the bacterial cell wall. The microbiological activity was correlated to the chemical properties of the substituent on C3.