RESUMO
Currently, pyripyropeneâ A, which is isolated from the culture broth of Aspergillus fumigatus FO-1289, is the only compound known to strongly and selectively inhibit the isozyme sterol O-acyltransferaseâ 2 (SOAT2). To aid in the development of new cholesterol-lowering or anti-atherosclerotic agents, new A-ring simplified pyripyropeneâ A analogues have been designed and synthesized based on total synthesis, and the results of structure-activity relationship studies of pyripyropeneâ A. Among the analogues, two A-ring simplified pyripyropeneâ A analogues exhibited equally efficient SOAT2 inhibitory activity to that of natural pyripyropeneâ A. These new analogues are the most potent and selective SOAT2 inhibitors to be used as synthetic compounds and attractive seed compounds for the development of drug for dyslipidemia, including atherosclerotic disease and steatosis.