A GLYCOSYLPHOSPHATIDYLINOSITOL-ANCHORING INHIBITOR WITH AN UNUSUAL TETRACARBOCYCLIC SESTERTERPENE SKELETON FROM THE FUNGUS CODINAEA SIMPLEX

A novel sesterterpene, YW3699, was isolated from fermentation of the f ungus Codinaea simplex. Based on spectroscopic evidence, including UV, IR, FAB-MS, ESI-HRMS, H-1 and C-13 NMR, DQ-COSY, HQSC and HMBC, YW369 9 was shown to have an unusual tetracarboxylic sesterterpene skeleton. Its relative stereochemistry and solution conformation were elucidate d with H-1-H-1 coupling constants and detailed analysis of its ROESY s pectrum, in conjunction with inspection of Dreiding stereomodels. A po ssible biosynthetic route for YW3699 via the mevalonate pathway is pro posed and discussed. YW3699 was found to be an inhibitor of glycosylph osphatidylinositol (GPI) synthesis with a MIC of 3.5 mu M. (C) 1998 El sevier Science Ltd. All rights reserved.