RESUMO
The conversion of [2-deutero-3-fluoro-D-Ala8]cyclosporin A (1) to a dehydroalanine analog [delta-Ala8]cyclosporin A (2) was achieved with lithium diisopropylamide in THF at low temperature. This dehydro compound is a useful intermediate for the preparation of position 8 analogs of cyclosporin A formed from it by the conjugate addition of thiol compounds. NMR conformational studies have provided evidence for the restoration of D-stereochemistry in the modified Ala8 residues. The preparation of several of these cyclosporin analogs and their bioactivities are described.
Assuntos
Ciclosporinas/química , Imunossupressores/química , Ativação Linfocitária , Linfócitos T/efeitos dos fármacos , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Ciclosporinas/farmacologia , Feminino , Imunossupressores/farmacologia , Espectroscopia de Ressonância Magnética , Camundongos , Camundongos Endogâmicos C57BL , Conformação Molecular , Espectrometria de Massas de Bombardeamento Rápido de ÁtomosRESUMO
Paraherquamide and six novel analogs were isolated from the fermentation of Penicillium charlesii (ATCC 20841). All seven natural products displayed potent antinematodal activity against Caenorhabditis elegans. None of the novel analogs were more potent than paraherquamide.
Assuntos
Anti-Helmínticos/isolamento & purificação , Antinematódeos/isolamento & purificação , Caenorhabditis/efeitos dos fármacos , Indolizinas/isolamento & purificação , Penicillium/metabolismo , Compostos de Espiro/isolamento & purificação , Animais , Anti-Helmínticos/farmacologia , Antinematódeos/farmacologia , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Meios de Cultura , Fermentação , Indolizinas/farmacologia , Microbiologia do Solo , Compostos de Espiro/farmacologiaRESUMO
At least six distinct beta-lactam antibiotics of the epithienamycin family are produced by a strain of Streptomyces flavogriseus MB 4638. Each of the six can be isolated in substantially pure form by column chromatography using Dowex 1, Amberlite XAD-2 and Biogel packings. The structures were established by comparison of the ultraviolet, proton magnetic resonance and mass spectral characteristics with those of thienamycin and its derivatives. All six compounds contain the carbapenem ring system which is also found in thienamycin. They differ from each other and from thienamycin by chemical modifications and/or stereoisomerism. Enzymatically deacetylated epithienamycin A has the properties of an isomer of thienamycin.
Assuntos
Antibacterianos/isolamento & purificação , Lactamas/isolamento & purificação , Tienamicinas , Fenômenos Químicos , Química , Lactamas/análise , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estereoisomerismo , Streptomyces/análiseRESUMO
The avermectins, a family of new anthelmintic agents, were isolated from the mycelia of Streptomyces avermitilis. Four closely related major components and four homologous minor components were separated from the complex. Solvent extraction, solvent partition, and adsorption methods were used to isolate and purify the complex; novel partition chromatography systems using Sephadex LH-20 were used to separate the components. A reverse-phase high-pressure liquid chromatography assay for the quantitative determination of all components was used extensively to monitor the purification methods.
Assuntos
Anti-Helmínticos/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Cristalização , MétodosRESUMO
Cephamycins A and B were isolated from the same fermentation broth of various actinomycetes by adsorption and ion-exchange methods. The antibiotics were separated from each other by column chromatography on a dextran-based ion-exchange resin. Cephamycin C was isolated from a different fermentation broth by ion-exchange and gel-filtration methods. The chemical characteristics of these new antibiotics were determined.