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

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 Mosherʹs method.