THE STRUCTURES OF A10255B, A10255G, AND A10255J - NEW THIOPEPTIDE ANTIBIOTICS PRODUCED BY STREPTOMYCES-GARDNERI

The structures of the major members of a new family of important thiopeptide antibiotics, A10255B (1), A10255G (15), and A10255J (16), produced by Streptomyces gardneri (NRRL 15537), are described. Selective chemical degradation in combination with NMR, FABMS, and CID methods on the degradation products was required to solve these structures. Methanolysis of 1 resulted in the isolation of 4-carbomethoxy-2-propionyloxazole (8) and dimethyl sulfomycinamate (9) as well as N-((acetamidomethyl)thiazolyl)-1-(carbomethoxythiazolyl)ethanamide (11) after acetylation. Vigorous treatment with acid produced berninamycinic acid (10). Trifluoroacetolysis led to cleavage at the six dehydroalanine (deala) residues to give a complex and highly modified pentapeptide 12 which was sequenced by CIDMS and NMR techniques. Compound 12 was composed of the following: sulfo-mycinamic acid, threonine, 1-(4-carboxyoxazolyl)-1-aminopentene unit (dehydronorvaline masked by oxazole at its carboxyl group), 2-(aminomethyl)thiazole-4-carboxylic acid, and 2-(1-aminoethyl)-4-carboxamidothiazole. FABMS and base hydrolysis showed that 1 had a deala tetrapeptide side chain. Antibiotics 15 and 16 each had a masked dehydrobutyrine in place of the dehydronorvaline present in 1, and 16 had a single amidated deala as a side chain.