45 新しい作用機序をもつNocardia由来の免疫抑制物質(口頭発表の部)

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In our continuing search for bioactive metabolites from microorganisms, we isolated a novel terpenoid, brasilicardin A (1), and a new 32-membered macrolide, brasilinolide A (2), possessing potent immunosuppressive activity from the cultured broth of the actinomycete Nocardia brasiliensisIFM0406. Here we describe the isolation and structure elucidation of 1 and 2. Brasilicardin A (1) was shown to have the molecular formular, C_<45>H_<68>N_2O_<16>, by HRFABMS. The ^1H and ^<13>C NMR spectra of 1 indicated the presence of two sugar units, hydrocarbon rings, 3-hydroxybenzoate, and amino acid moiety. The planar structure of 1 was elucidated by extensive analyses of the ^1H-^1H COSY, HMQC, and HMBC spectra and the relative stereochemistry was assigned by the ROESY spectrum. GC and amino acid analyses of methanolysis and acid hydrolysis product of 1 revealed that the two sugar units were assigned to be rhamnose and glucosamine. The absolute stereochemistry of terpenoid moiety of 1 was elucidated by using CD exciton chirality method for tris-(4-dimethylaminobenzoate) derivative (3) of 1. The molecular formula of brasilinolide A (2) was determined to be C_<57>H_<98>O_<24> by the HRFABMS. Compound 2 possessed a sugar moiety and polyhydroxy parts suggested by ^1H and ^<13>C NMR data. The presence of 2-deoxyfucopyranose was elucidated by GC analysis of methanolysis product of 2. The partial structures a〜e of 2 were deduced from detailed analyses of the 2D NMR spectra. The connectivities among these patial structures a〜e were elucidated by the HMBC and HMQC-HOHAHA spectra. The relative stereochemistry of a tetrahydropyran ring in 2 was deduced from the NOESY spectrum. Brasilicardin A (1) is a novel tricyclic diterpenoid containing an amino acid moiety and a rhamnose and an N-acetylglucosamine units, while brasilinolide A (2) is a new 32-membered macrolide with a tetrahydropyran ring and a 2-deoxyfucopyranose. Compounds 1 and 2 exhibited potent immunosuppressive activity in mouse mixed lymphocyte assay. Brasilicardin A (1) showed cytotoxicity against adriamycin-resistant murine leukemia P388/ADM, while brasilinolide A (2) showed antifungal activity against Aspergillus niger.
天然有機化合物討論会の論文
1997-07-20

45 新しい作用機序をもつNocardia由来の免疫抑制物質(口頭発表の部)

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