ABSTRACT
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.
Subject(s)
Cyclosporins/chemistry , Immunosuppressive Agents/chemistry , Lymphocyte Activation , T-Lymphocytes/drug effects , Animals , Chromatography, High Pressure Liquid , Chromatography, Thin Layer , Cyclosporins/pharmacology , Female , Immunosuppressive Agents/pharmacology , Magnetic Resonance Spectroscopy , Mice , Mice, Inbred C57BL , Molecular Conformation , Spectrometry, Mass, Fast Atom BombardmentABSTRACT
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.
Subject(s)
Anthelmintics/isolation & purification , Antinematodal Agents/isolation & purification , Caenorhabditis/drug effects , Indolizines/isolation & purification , Penicillium/metabolism , Spiro Compounds/isolation & purification , Animals , Anthelmintics/pharmacology , Antinematodal Agents/pharmacology , Chromatography, High Pressure Liquid , Chromatography, Thin Layer , Culture Media , Fermentation , Indolizines/pharmacology , Soil Microbiology , Spiro Compounds/pharmacologyABSTRACT
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.
Subject(s)
Anti-Bacterial Agents/isolation & purification , Lactams/isolation & purification , Thienamycins , Chemical Phenomena , Chemistry , Lactams/analysis , Magnetic Resonance Spectroscopy , Mass Spectrometry , Stereoisomerism , Streptomyces/analysisABSTRACT
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.
Subject(s)
Anthelmintics/isolation & purification , Chromatography, High Pressure Liquid , Chromatography, Thin Layer , Crystallization , MethodsABSTRACT
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.
