Pneumocandins from Zalerion arboricola. I. Discovery and isolation.

HPLC bioautography of the directed biosynthesis of Zalerion arboricola led to the discovery of pneumocandin B0 (L-688,786), a new antifungal and anti-Pneumocystis carinii lipopeptide. Isolation techniques were developed to separate this component from pneumocandin A0 (L-671,329) in fermentations of a mutant of Zalerion arboricola. A number of related compounds were also isolated, which differ from pneumocandins A0 and B0 in the hydroxylation patterns on the ornithine, homotyrosine, and proline.     

Pneumocandins from Zalerion arboricola. II. Modification of product spectrum by mutation and medium manipulation.

Zalerion arboricola ATCC 20868 produces pneumocandin A0 (L-671,329), a cyclic hexapeptide with a dimethylmyristic acid side chain. This compound has anti-candida and anti-pneumocystis activities. We were interested in looking for other related compounds produced by this organism. To facilitate this search, a simple medium (S2) composed of D-mannitol, peptonized milk, lactic acid, glycine, KH2PO4 and trace elements, which supported the production of a number of such compounds, was designed. For the isolation of mutants, either spores or growing mycelia were treated with N-nitroso-N-methylurethane or N-methyl-N'-nitro-N-nitrosoguanidine and survivors were screened for changes in the product spectrum. From approximately 1,500 survivors tested, 5 mutants were isolated. Mutants ATCC 20957, 74030, 20958 and 20988 exclusively produce various pneumocandins other than A0. These compounds were active against Candida and Pneumocystis carinii. The yield of A0 was found to be increased 2.5-fold over that of the parent in the fifth mutant, MF5415. Further medium studies indicated that the addition of soybean oil to S2 medium improved the yields. Subsequent development of another series of media containing Pharmamedia as a nitrogen source resulted in increase in production by 10- approximately 20-fold. Overall, these studies resulted in substantial improvement in the production of A0 as well as discovery and/or facile production of 7 other related compounds.     

Pneumocandins from Zalerion arboricola. IV. Biological evaluation of natural and semisynthetic pneumocandins for activity against Pneumocystis carinii and Candida species.

A series of lipopeptide compounds co-produced during the fermentation of pneumocandin A0 (L-671,329) and related semisynthetic compounds were evaluated in vivo against Pneumocystis carinii pneumonia and systemic candidiasis. In addition, they were tested in vitro against a panel of pathogenic Candida species and in a Candida membrane 1,3-beta-D-glucan synthesis assay. The results of these studies demonstrate that pneumocandin A0 and pneumocandin B0 (L-688,786) are the most potent compounds when considering both antipneumocystis and anticandida activity. Other compounds in the series are selectively more potent against P. carinii or Candida albicans suggesting a diverging structure-activity relationship. Evaluation of these compounds for their ability to inhibit C. albicans 1,3-beta-D-glucan synthesis in vitro demonstrates that they inhibit this process. A positive correlation between 1,3-beta-D-glucan synthesis inhibition and in vitro antifungal activity was also demonstrated for some of the pneumocandins.     

丝状真菌Zalerion arboricola来源的抗真菌化合物pneumocandin B0的分离纯化

pneumocandin B0(PB0)是新型棘白菌素类抗真菌药物卡泊芬净的前体.通过离心、溶剂抽提和大孔树脂脱色等方法从丝状真菌Zalerion arboricola发酵液中分离PB0,得到纯度为77.6%的PB0粗制品,进一步纯化后,得到纯度为97.2%的PB0精制品.     

Oximidine III, a new antitumor antibiotic against transformed cells from Pseudomonas sp. II. Structure elucidation

The structure of oximidine III, a new antitumor antibiotic against transformed cells from Pseudomonas sp. QN05727, was determined to be a benzolactone enamide containing an O-methyloxime moiety as shown in Fig. 1 by NMR spectral analysis including a variety of two-dimensional techniques.     

Metabolism of thymoxamine. III. Structure elucidation of the metabolites and interspecies comparison

The structures of six metabolites were elucidated using rat urine after intragastric administration of 14C-thymoxamine by means of enzyme incubations, mass spectrometry and synthesis of metabolites: desacetylthymoxamine, N-demethyl-desacetylthymoxamine, the corresponding sulfates and glucuronides. The nature of the conjugates was confirmed by biosynthesis, i.e., co-administration of unlabelled thymoxamine and 35S-sulfate or 14C-glucose. The system high performance liquid chromatography-radioactivity detection was used for interspecies comparison. All biotransformation pathways are seen in rat and man. In dog and cat demethylation is a very minor reaction. Glucuronidation is not observed in the cat.     

Ramoplanin (A-16686), a new glycolipodepsipeptide antibiotic. III. Structure elucidation

By combination of chemical, 1H and 13C NMR, and mass spectrometric studies, the structures of the three components of the antibiotic ramoplanin (A-16686), produced by Actinoplanes sp. ATCC 33076, have been elucidated. All the components have structures formed by a common depsipeptide skeleton carrying a dimannosyl group and are differentiated by the presence of various acylamide moieties, derived from C8, C9 and C10 fatty acids.     

Chloropolysporins A, B and C, novel glycopeptide antibiotics from Faenia interjecta sp. nov. III. Structure elucidation of chloropolysporins

Structure elucidations of chloropolysporins A, B and C were achieved mainly by chemical degradation studies. These components possessed the same pseudoaglycone in common and their structures were closely related to that of beta-avoparcin. The structures of chloropolysporins differ from that of beta-avoparcin in the presence of vancomycinic acid moiety instead of monodechlorovancomycinic acid moiety and glucose, not ristosaminylglucose, in its side chain. Chloropolysporin C was identified as derhamnosylchloropolysporin B based on its 1H NMR and mass spectral analysis and degradation studies. Two minor components, chloropolysporins D and E, were identified as the epimers of each of chloropolysporins B and C, respectively, based on their Cotton effects and retention times on reverse phase HPLC.     

Aranorosin, a novel antibiotic from Pseudoarachniotus roseus. II. Structure elucidation

Aranorosin, a new antifungal antibiotic, has been isolated from the culture filtrate and mycelium of a strain of Pseudoarachniotus roseus Kuehn. The antibiotic, C23H33NO6, contains a novel 1-oxaspiro[4,5]decane ring system. The structure (I) has been elucidated on the basis of spectroscopic and chemical analysis.     

Structure elucidation of Sch 725674 from Aspergillus sp

A new macrolide Sch725674 (1) was isolated and identified from the culture of an Aspergillus sp. The structure elucidation of 1 was accomplished based on extensive NMR spectroscopic analyses. Compound 1 showed inhibitory activity against Saccharomyces cerevisiae (PM503) and Candida albicans (C43) with MICs of 8 and 32 microg/ml, respectively.     

Argyrins,immunosuppressive cyclic peptides from myxobacteria. II. Structure elucidation and stereochemistry

The structures of argyrins A-H were elucidated by NMR spectroscopy, chemical degradation and X-ray analysis as cyclic octapeptides. Argyrins A and B, in addition to the common amino acids tryptophan, glycine, dehydroalanine and alanine or alpha-aminobutyric acid, sarcosine, contain 2-(1-aminoethyl)thiazol-4-caboxylic acid and the novel amino acid 4'-methoxytryptophan. In argyrins C and D the latter is replaced by 4'-methoxy 2'-methyltryptophan. According to NMR analysis the solution and crystal conformations of argyrins A and B are identical in CDCl3 and slightly different in acetone-d6. Argyrins A and B are identical with the antibiotics A21459 A and B, whose structures are revised with respect to 4'-methoxytryptophan.     

Structure elucidation of gestodene

The structure of 17 alpha-ethinyl-17 beta-hydroxy-18-methyl-4,15-estradien-3-one (gestodene) was elucidated by the spectrometric methods UV, IR, NMR, MS.     

Structure elucidation of ficellomycin

The structure of ficellomycin, an antibiotic previously discovered by Argoudelis et al., is elucidated as valyl-2-[4-guanidyl-1-azabicyclo[3.1.0]hexan-2-yl]glycine (1) by NMR, MS, and derivatization studies. The 1-azabicyclo[3.1.0]hexane moiety in 1 represents an unusual ring system making ficellomycin a unique natural product compound.     

Asperlicin, a novel non-peptidal cholecystokinin antagonist from Aspergillus alliaceus. Structure elucidation

Asperlicin (1, C31H29N5O4) is a novel cholecystokinin antagonist produced by Aspergillus alliaceus. The structure of asperlicin has been determined by NMR and mass spectral analysis, and X-ray crystallography.     

头孢菌素中间体GCLE的主要相关杂质研究

GCLE是合成头孢类抗生素的重要中间体,通过青霉素开环物的苯磺酸酯氯代、环合而合成的GCLE经HPLC分析含有三个主要杂质.本文采用定向合成和正相HPLC分离制备方法获得了三个主要相关杂质单体,并通过NMR对它们进行了结构确证.经解析确认:杂质Ⅰ为GCLE的△3-异构体;杂质Ⅱ为3位甲基相关物;杂质Ⅲ为2位保护基上3'氯取代相关物.     

Bioxanthracenes from the insect pathogenic fungus Cordyceps pseudomilitaris BCC 1620. II. Structure elucidation

Structures of eleven bioxanthracenes (1 approximately 11) and two monomers (12 and 13), isolated from the insect pathogenic fungus Cordyceps pseudomilitaris BCC 1620, were elucidated. The structure, including the axial stereochemistry, of one of the major symmetrical dimers (1) was determined by X-ray crystallographic analysis, while the stereochemistries of the other isomers were deduced by chemical conversions and spectroscopic means.     

Glomosporin, a novel antifungal cyclic depsipeptide from Glomospora sp. II. Structure elucidation

The structure of glomosporin, an antifungal antibiotic, was elucidated by NMR and MS spectroscopic studies. Glomosporin is a novel cyclic depsipeptide with an amino acid sequence Ser-Ala-Asp-Asn-Asn-Ser-Thr, and a 3,4-dihydroxy-4-methylhexadecanoic acid side chain.     

一种新强心苷类化合物的结构鉴定及其活性研究

目的 从弯蕊开口箭（Tupistra wattii Hook.f.）中寻找抗癌活性先导化合物。方法 使用稻瘟霉活性筛选体系进行活性追踪分离，并通过波谱分析，特别是二维核磁手段结合化学方法对分离得到的化合物进行结构鉴定。结果 从弯蕊开口箭中分离得到3个具有很强细胞毒活性的强心苷，其中化合物2wattosideF是一个新化合物，并且它的细胞毒活性在3个强心苷中最强，其IC50值为0.011μmol/L。结论 wattoside F是一个具有很强细胞毒活性的新的强心苷类化合物。