Synthesis of(-)-Berkelie Acid

摘要

Stierle and co-workers recently isolated berkelic acid(1)from an acid mine waste fungal extremophile(Scheme 1).The structure was determined to be a novel spiroketal from the analysis of the NMR and mass spectral data.The relative stereochemistry of the side-chain stereocenter(C22)and the absolute stereochemistry were not assigned.Berkelic acid inhibits MMP-3 and caspase-1 and shows selective activity toward ovarian cancer OVCAR-3 with a GI_(50)of 91 nM.This potent and selective activity and its limited accessibility from natural sources make it a significant synthetic target.