CHEMICAL MODIFICATION AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF PYRIPYROPENES .3. SYNTHETIC CONVERSION OF PYRIDINE-PYRONE MOIETY

Structure-activity relationships of the pyridine-pyrone moiety in pyri pyropene A (1), a potent acyl-CoA:cholesterol acyltransferase (ACAT) i nhibitor of fungal origin, were studied. Several kinds of aromatic or hetero ring substituents for the pyridine moiety were synthesized usin g unique degradation reaction, following by gamma-acylation. All the s ix synthesized analogs decreased the inhibitory activity with 20 to 20 0 times larger IC50 values than that of 1. Furthermore, the pyridine-p yrone substituent also dramatically decrease the inhibitory activity. Thus, the pyridine-pyrone moiety is important for eliciting potent ACA T inhibition.