Chemical modification and structure-activity relationships of pyripyropenes. 2. 1,11-Cyclic analogs.

A series of 1,11-cyclic analogs of pyripyropene A were prepared. Replacement of the 1,11-acyl groups of pyripyropenes with 1,11-cyclic acetals effectively improved in vitro acyl CoA:cholesterol acyltransferase (ACAT) inhibitory activity. Especially noteworthy is benzylidene acetal analog 35, the most potent inhibitor (IC50 = 5.6 nM) among the derivatives prepared so far, which showed 16 times more potent inhibitory activity than pyripyropene A.