RESUMO
Streptomyces sp. X-14889 (NRRL 15517) has been found to produce a number of novel polyether antibiotics and an orange pigment. One of the antibiotics, X-14889B (3) was identified as ferensimycin A, which in turn is an isomer of the well-studied polyether antibiotic, lysocellin (1). Of the three other antibiotics, X-14889C (4) is a lower homolog of ferensimycin A and antibiotics X-14889A (2) and D (5) which are respectively the descarboxy and anhydro-descarboxy forms of this same molecule. The latter compound, X-14889D is of interest as it contains an ether bridge across the terminal tetrahydrofuranyl ring in an analogous relationship to that reported earlier for antibiotics X-14873A (6) and G.
Assuntos
Antibacterianos/isolamento & purificação , Streptomyces/metabolismo , Antibacterianos/química , Furanos/química , Furanos/isolamento & purificação , Conformação Molecular , Difração de Raios XRESUMO
Streptomyces sp. X-14873 (ATCC 31679) has been found to produce a number of secondary metabolites. Three have been identified as the novel actinomycins, X-14873B, C and D, each of which contains both proline and 3-hydroxy-5-methylproline. Potentially, the most important microbial product from this fermentation is the novel polyether antibiotic X-14873A which differs from lysocellin only in the substituents at carbons C-4 and C-5 in the tetrahydropyranyl ring. The methyl group and proton in lysocellin are replaced by an ethyl and hydroxyl group, respectively in X-14873A. In addition, two other novel polyethers, X-14873H and G, were isolated and shown to differ from 1 in lacking a carboxyl group and in the case of 3, possessing an ether bridge across the terminal tetrahydrofuranyl ring system.
Assuntos
Antibacterianos/isolamento & purificação , Dactinomicina/análogos & derivados , Dactinomicina/isolamento & purificação , Streptomyces/metabolismo , Animais , Fenômenos Químicos , Química , Cristalização , Camundongos , Conformação Molecular , TálioRESUMO
Antibiotic X-14885A is a polyether antibiotic belonging to the class of these natural acid ionophores known as pyrrolethers. The structure of the antibiotic was elucidated by X-ray crystallographic analysis of the hydrated sodium salt, which crystallized as a tetramer containing four antibiotic and water molecules and four atoms of sodium. Antibiotic X-14885A differs from the most well-known member of the class, A-23187, in two respects: the aromatic N-methylamino group present in the latter is replaced by a phenolic hydroxyl, and one of the four aliphatic methyls is replaced by a proton. Antibiotic X-14885A is active against Gram-positive bacteria and the spirochete, Treponema hyodysenteriae.
Assuntos
Antibacterianos/isolamento & purificação , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Conformação Molecular , Piranos/isolamento & purificação , Piranos/toxicidade , Especificidade da Espécie , Relação Estrutura-Atividade , Treponema/efeitos dos fármacos , Difração de Raios XRESUMO
Conversion of the monovalent polyether antibiotic monensin into a series of urethane derivatives substituted at C-26 causes a ten-fold increase in the cation transporting properties of the antibiotic as well as making the resulting semisynthetic urethanes divalent ionophores. These changes must in part account for the enhanced antimicrobial activities of the urethanes. The most active derivatives are the phenylurethanes which are ten times more active in vitro against Gram-positive bacteria and unlike monensin are active against Candida albicans and Penicillium digitatum. Another novel activity exhibited by four of the urethanes was against Plasmodium berghei, the causative agent for malaria.
Assuntos
Antibacterianos/síntese química , Furanos , Monensin/análogos & derivados , Cátions Bivalentes , Avaliação Pré-Clínica de Medicamentos , Fungos/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Ionóforos , Testes de Sensibilidade Microbiana , Relação Estrutura-AtividadeRESUMO
Antibiotics X-14667A (1) and X-14667B (2) are novel monovalent polyether antibiotics of the spiroketal type isolated from fermented cultures of Streptomyces cinnamonensis subsp. urethanofaciens together with monensin (3), its lower homolog, factor B (4) and 1,3-diphenethylurea (6). By a combination of microanalysis, mass spectrometry and 13C nmr, antibiotics X-14667A and B have been shown to be natural 2-phenethylurethanes of monensin B and A respectively. Both structures have been confirmed by reacting the appropriate monensin with 2-phenethylisocyanate to yield semi-synthetic compounds that are identical to the natural products.
Assuntos
Antibacterianos/isolamento & purificação , Furanos/isolamento & purificação , Monensin/isolamento & purificação , Antibacterianos/síntese química , Antibacterianos/metabolismo , Fenômenos Químicos , Química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Monensin/análogos & derivados , Monensin/síntese química , Monensin/metabolismoRESUMO
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(+)-1-amino-1-(4-bromophenyl)-ethane salt contained pyrrole carbonyl and trans-butadienyl chromophores in addition to the unusual tetrahydroindane bicyclic ring system. A second novel metabolite was identified as 3-ethyl-1,3-dihydro-3-methoxy-2H-indol-2-one.