ZG-1494-ALPHA, A NOVEL PLATELET-ACTIVATING-FACTOR ACETYLTRANSFERASE INHIBITOR FROM PENICILIUM-RUBRUM, ISOLATION, STRUCTURE ELUCIDATION AND BIOLOGICAL-ACTIVITY

A novel inhibitor of platelet-activating factor (PAF) acetyltransferas e, an essential enzyme in the remodeling pathway of platelet-activatin g factor synthesis, was identified by a high throughput screen of natu ral product extracts of microbial origin. The compound, ZG-1494 alpha, was isolated from an ethyl acetate extract of a culture broth of Peni cillium rubrum through bioassay guided fractionation. The structure of ZG-1494 alpha was determined by spectroscopic methods. A key feature of the structure, which is relatively rare among natural products, is the 5-hydroxy-3-pyrrolin-2-one moiety. A C-13-C-13 INADEQUATE was util ized to unambiguously determine the regiochemistry of this molecule.