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 fungus Codinaea simplex. Based on spectroscopic evidence, including UV, IR, FAB-MS, ESI-HRMS, 1H and 13C NMR, DQ-COSY, HQSC and HMBC, YW3699 was shown to have an unusual tetracarbocyclic sesterterpene skeleton. Its relative stereochemistry and solution conformation were elucidated with 1H-1H coupling constants and detailed analysis of its ROESY spectrum, in conjunction with inspection of Dreiding stereomodels. A possible biosynthetic route for YW3699 via the mevalonate pathway is proposed and discussed. YW3699 was found to be an inhibitor of glycosylphosphatidylinositol (GPI) synthesis with a MIC of 3.5 μM.