Jun Kohno

Isolation and structure determination of TMC-151s: Novel polyketide antibiotics from Gliocladium catenulatum Gilman & Abbott TC 1280.

Abstract Six new antibiotics, TMC-151 A-F (2–7) have been isolated from organic extracts of the fermentation broth of Gliocladium catenulatum Gilman & Abbott TC 1280, isolated from a soil sample. Their structures including the absolute stereochemistries, were determined by extensive analyses of NMR and X-ray crystallography, and degradation studies. TMC-151s are novel polyketides containing D-mannopyranoside and D-mannitol or D-arabitol. These antibiotics showed moderate cytotoxicity to several tumor cell lines.

STRUCTURES OF TMC-120A, B AND C, NOVEL ISOQUINOLINE ALKALOIDS FROM ASPERGILLUS USTUS TC 1118

Abstract Three novel isoquinoline alkaloids, TMC-120A, B and C ( 1–3 ) have been isolated from a fermentation broth of Aspergillus ustus (Bain.) Thom & Church TC 1118, a fungus isolated from rhizosphere of grass. Their structures were determined through extensive spectroscopic analyses and chemical studies. TMC-120s ( 1–3 ) are found to be the first furo[3,2- h ]isoquinoline-type alkaloids isolated from natural sources.

Trierixin, a Novel Inhibitor of ER Stress-induced XBP1 Activation from Streptomyces sp. : II. Structure Elucidation

Trierixin, a new member of the triene-ansamycin group, has been isolated from the fermentation broth of Streptomyces sp. AC654 as an inhibitor of ER stress-induced XBP1 activation. The structure of trierixin was determined on the basis of its spectroscopical and chemical properties. Trierixin possessed a 21-membered macrocyclic lactam, which contains a methylthio-benzenediol structure, and a cyclohexanecarbonylalanine moiety. Trierixin is thus elucidated as 21-thiomethylmycotrienin II.

Structure of TMC-69, a new antitumor antibiotic from Chrysosporium sp. TC 1068

Abstract A new antitumor antibiotic, TMC-69, possessing inhibitory activity against cdc25A phosphatase, has been isolated from the fermentation broth of a mitosporic fungus, Chrysosporium sp. TC 1068. This antibiotic was labile in solid state as well as in solution, and thus was converted to the more stable derivatives, diacetyl TMC-69 and hexahydro TMC-69, to elucidate the structure and to evaluate the biological activities. The planar structure of TMC-69 was determined, through the analysis of various NMR experiments of diacetyl TMC-69 and ESI-MS data of TMC-69, to be [5Z(E,E)]-1,4-dihydroxy-5-phenyl-3-[tetrahydro-3-methyl-5-(6-methyl-2,4-octadienylidene)-2H-pyran-2-yl]-2(1H)-pyridinone. Furthermore, the absolute configuration of tetrahydropyranyl moiety was determined by degradation studies of TMC-69, followed by the application of modified Moshers method.

Production of TMC- 151, TMC- 154 and TMC- 171, a new class of antibiotics, is specific to ‘Gliocladium roseum’ group

A novel class of fungal metabolites, TMC-151, TMC-154, and TMC-171 series compounds, was found exclusively inGliocladium catenulatum, Clonostachys rosea and closely related strains. These compounds were not detected in any other fungi examined. The production spectrum of each component was correlated to the morphology of the secondary conidiophores and the conidia. TMC-151 was limited toClonostachys rosea (formerlyG. roseum) forming navicular or reniform conidia orG. catenulatum with gray-green conidial masses, whereas TMC-154 and 171 were limited to the strains closely related toGliocladium roseum, which grew more slowly and formed more symmetrical conidia.