The First Total Synthesis of a Pyripyropene-Type ACAT Inhibitor, (±)-GERI-BP001

摘要

GERI-BP001 (1) is a natural product which was isolated in 1994 from the culture broth of Aspergillus fumigatus F37. Like its structural relatives, the py-ripyropenes A—D (2), it is an inhibitor of acyl-CoA: cholesterol acyltransferase (ACAT), the enzyme responsible for the intracellular esterification of cholesterol. There is evidence that ACAT inhibitors may lower plasma cholesterol levels and prevent the accumulation of cholesterol esters in arterial lesions. Therefore, members of this class are viewed as being potentially effective for the treatment of atherosclerosis and hypercholester-olemia. Herein we describe an efficient preparation of GERI-BP001 by a scheme which is envisioned as a prototype for the synthesis of the more highly oxygenatedand more potent pyripyropenes (2).