Frank Gentile

Two novel diketopiperazines isolated from the fungus Tolypocladium sp.

Abstract Diketopiperazines, Sch 54794 and Sch 54796, have been isolated from a fungal fermentation. The structures of these compounds have been established based on spectroscopic data analysis. Sch 54794 exhibited inhibitory activity in the platelet activating factor (PAF) assay.

A New Actinomycin Complex Produced by a Micromonospora Species: Fermentation, Isolation, and Characterization

A species of Micromonospora, Micromonospora floridensis NRRL 8020, has been found to produce an actinomycin complex consisting of at least 25 active components. After solvent extraction of the complex, separation of the individual components was carried out by preparative thin-layer chromatography. Hydrolysis and subsequent electrophoretic and chromatographic identification of the amino acid content of each of the isolated components have shown differences from known actinomycins, and the probability exists that these contain a number of amino or imino acids not previously found in other members of this group of antibiotics.

Isolation and structure elucidation of two novel deformylase inhibitors produced by Streptomyces sp.

Abstract Sch 382582 ( 1 ) and Sch 382583 ( 2 ), two novel pseudopeptides, were isolated from fermentation broth of Streptomyces sp. as bacteria peptide deformylase inhibitors. Structure elucidation of 1 and 2 was accomplished by extensive 2D NMR spectroscopic studies including NOESY, HMQC-TOCSY and HMBC experiments, and the relative stereochemistry was determined by X-ray crystallography. Both compounds displayed potent inhibitory activity against E. coli deformylase.

A Novel Macrolactam-trisaccharide Antifungal Antibiotic Taxonomy, Fermentation, Isolation, Physico-chemical Properties, Structure Elucidation and Biological Activity

A novel secondary metabolite SCH 42282 (1), with antifungal activity was isolated from the fermentation broth of a soil actinomycete identified as a Microtetraspora sp. The active compound was separated from the fermentation broth by butanol extraction and purified on a silica gel column and by multi-coil counter current chromatography. The compound was identified as a novel macrolactam trisaccharide related to SCH 38518 (4). The structure was established by hydrolysis of the parent compound and spectroscopic studies of the acetate derivative. The compound is active against Candida spp. (Geometric Mean MICs. 18 micrograms/ml) but less active SCH 42729 (3). the disaccharide (Geometric Mean MICs, > or = 10.7 micrograms/ml and SCH 38518 (4), the monosaccharide (Geometric Mean Mics, 3.8 micrograms/ml.

Enhancement of secondary metabolite production using the antibiotic gradient-plate technique

We have used the antibiotic gradient-plate technique to generate antifungal producing Actinomadura strains that synthesize enhanced quantities of component 3A of a macrocyclic lactam antifungal compound Sch 38516. Seventy-nine colonies were selected from a mixture of rifampicin and spectinomycin gradient plates. The two fermentation extracts described produced an enhanced 3A component (identified with silica gel TLC, HPLC, and bioautography) when compared to the parent culture isolate extracts (no antibiotic selection).