3 Amphidinolide GおよびHの立体化学、生合成、構造活性相関に関する研究(口頭発表の部)

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Amphidinolides G (1) and H (2), potent cytotoxic 27- and 26-membered macrolides, respectively isolated from marine dinoflagellates Amphidinium sp. (strain number Y-25). Recently we found new strains (Y-72 and Y-42) of the genus Amphidinium producing relatively large amount of 1 and 2. Here we describe the determination of relative and absolute stereochemistry of these compounds on X-ray diffraction analysis, synthesis of degradation product (3) of amphidinolide H (2), and interconversion between 1 and 2. We also isolated six new macrolides 3〜8 related to amphidinolides G (1) and H (2) from the Y-42 strain of dinoflagellates Amphidinium sp. The structures of compounds 3,4,5, and 6 were elucidated as 22-epi, 18-epi, 6,7-dihydro, and 6,7-dihydro-l8-epi forms of amphidinolide H (2), respectively, on the basis of detailed analyses of spectroscopic data including ^3J_<H,H>,^2J_<C,H>, and ^3J_<C.H> values and distance geometry calculation. On the other hand, the structures of compounds 7 and 8 were assigned as the 22-epi and 6,7-dihydro forms of amphidinolide G (1). Compounds 3 and 7 were as potent cytotoxic against L1210 and KB cells as amphidinolides G (1) and H (2), while cytotoxicity of compounds 4,5,6, and 8 were extremely weaker (1/100〜1/1000) than those of 1 and 2. These results indicated that allyl epoxide and stereochemistry of C-18 were important for its activity. The biosynthetic origins of amphidinolides G (1) and H (2) were investigated on the basis of 2D NMR data of ^<13>C-enriched samples obtained by feeding experiments with [1-^<13>C], [2-^<13>C], and [1,2-^<13>C_2] sodium acetates in cultures of a marine dinoflagellate Amphidinium sp. These incorporation patterns suggested that 1 and 2 were generated from three unusual C_2 units derived only from C-2 of acetates in addition to three successive polyketide chains. Furthermore it is noted that six oxygenated carbons of C-1, C-18, C-20, C-21, C-22, and C-26 in 1 and 2 were not derived from the C-1 carbonyl but from the C-2 methyl of acetates.
天然有機化合物討論会の論文
2000-10-01

3 Amphidinolide GおよびHの立体化学、生合成、構造活性相関に関する研究(口頭発表の部)

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