Isolation and characterization of antibiotic X-14547A, A novel monocarboxylic acid lonophore produced by streptomyces antibioticus NRRL 8167

Abstract

A novel carboxylic acid ionophore, antibiotic X-14547A, closely related to the polyether antibiotics has been isolated along with four other metabolites from fermented cultures of a new strain of Streptomyces antibioticus. The structure, determined by X-ray analysis of the R(+)-l-amino-l-(4-bromophenyl)-ethane sait contained pyrrole carbonyl and trans-butadienyl chrcmophores in addition to the unusual tetrahydroindane bicyclic ring system. A second novel metabolite was identified as 3-ethyl-l,3-dihydro-3-methoxy-2H-indol-2-one. Although the polyether antibiotics were first isolated in 19511, 2), the present high level of interest in these monocarboxylic acid ionophores began with the determination of the structure of monensin in 19673) and nigerian4) the following year. These two antibiotics obviously constituted a new class of ionophores as they had many new structural features in common as well as similar ion transporting properties whether determined by equilibrium complexation in a single phase or distribution in two phases5). One of the few differences between the two, was in their specific ionophore selectivity. Although both were shown to complex mono-, but not divalent, cations, monensin exhibits greatest affinity towards the Na+ cation, whereas nigericin forms complexes better with K+. [n contrast to these results, the third polyether to be structurally defined, lasalocid6,7), had both a different structure (aromatic chromophore, 3C-ethyls) and a strong affinity for divalent cations (Ba2+, Ca2+) as well as the monovalent type (Na+, K+). Since 1970, while more than twenty of the monovalent polyethers have been characterized (e.g. dianemycin8), lenoremycin (Ro 21-6150)9), salinomycin10), A204A11) the structure of only three of the lasalocid-like divalent type have been solved, namely lysocellin12), iso-lasalocid13) and A2318714). One of the latter, antibiotic A23187, contains a pyrrole-2-carbonyl moiety. The present report describes the characterization of a second novel pyrrole-ether (a recently proposed name for pyrrole containing monocarboxylic ionophores15), antibiotic X-14547A (1), which like lasalocid A forms complexes with both divalent and monovalent cations. © 1979, JAPAN ANTIBIOTICS RESEARCH ASSOCIATION. All rights reserved.