PURPACTINS, NEW INHIBITORS OF ACYL-CoA : CHOLESTEROL ACYLTRANSFERASE PRODUCEDBY Penicillium purpurogenum III. CHEMICAL MODIFICATION OF PURPACTIN A HlROYUKI NlSHIDA*,

Acylated drivatives of the C-Y and/or C-l l hydroxy group(s) of penicillide were synthesized and their inhibitory activity against acyl-CoA:cholesterol acyltransferase (ACAT) was studied. Introduction of long acyl group into either or both hydroxy residue(s) decreased the inhibitory activity. A small acyl moiety such as acetyl or rc-butyryl at the C-l' hydroxy group is responsible for potent inhibitory activity against ACAT. The r-Oacetyl-ll-0-tetrahydropyranyl derivative (l l-0-2"-tetrahydropyranylpurpactin A) showed high selectivity (cytotoxic dose vs. effective dose) in a cell assay using J774 macrophages.