CHEMICAL MODIFICATIONS OF THE ANTIBIOTIC PURPUROMYCIN

Purpuromycin, isolated in our laboratories from the culture broth of A ctinoplanes ianthinogenes, is very active in vitro against Gram-positi ve bacteria and fungi and shows variable activity against Gram-negativ e bacteria. Its poor bioavailability, probably due to its insolubility in aqueous media at physiological pH's, and the fact that its activit y is antagonized by serum, led us to plan a chemical program with the aim of understanding the relevance of the substituents for the antibio tic activity. The original 7-methoxycarbonyl group was transformed int o more hydrophilic groups by hydrolysis, by reduction and by ammonolys is or in esters with different degree of lipophilicity and steric hind rance. Almost all of the derivatives retained activity against Gram-po sitive bacteria but lost activity against Escherichia coli and Trichop hyton mentagrophytes. Like purpuromycin, all of the derivatives show a reduced activity in the presence of serum.