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 mito sporic fungus, Chrysosporium sp. TC 1068. This antibiotic was labile in sol id 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 structu re and to evaluate the biological activities. The planar structure of TMC-6 9 was determined, through the analysis of various NMR experiments of diacet yl TMC-69 and ESI-MS data of TMC-69, to be [SZ(E,E)]-1,4-dihydroxy-5-phenyl -3-[tetrahydro-3-methyl-5-(6-methyl-2,4-octadienylidene)-2H-pyran-2-yl]-2(I H)-pyridinone. Furthermore, the absolute configuration of tetrahydropyranyl moiety was determined by degradation studies of TMC-69, followed by the ap plication of modified Mosher's method. (C) 2001 Elsevier Science Ltd. All r ights reserved.