Absolute structure, biosynthesis, and anti-microtubule activity of phomopsidin, isolated from a marine-derived fungus Phomopsis sp.

The absolute configuration of phomopsidin, a marine-derived fungal metabolite from Phomopsis sp. isolated at Pohnpei, was determined by the exciton chirality method as 6S, 7S, 8S, 11S, 12R, and 15R. The biosynthetic study using C-13-labeled precursors revealed the origin of all carbon atoms in phomopsidin, which was built by nine acetates and three methyl groups from L-methionine. Inhibitory activities of phomopsidin and its Me ester derivative against microtubule assembly were examined together with the structurally related compounds MK8383, solanapyrones, and tanzawaic acids. Phomopsidin and its (16Z)-isomer (MK8383) showed anti-microtubule activity at IC50 of 5.7 and 8.0 muM, respectively, while the Me ester and other compounds were not active at 100 muM. (C) 2003 Elsevier Science Ltd. All rights reserved.