Synthesis and hypolipidemic activity of modified side chain alpha-asarone homologues

A series of homologues of alpha -asarone (1), containing variable size and functionality on the side chain attached to the aromatic ring, has been sub jected to a study of structure-activity relationship. For most of the prepa red derivatives, either with a carbonyl (8a-8e), a hydroxy group (9a-9e), o r with a conjugated double bond (10a-10d), significant effects on serum lip oprotein cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides we re displayed. The results showed an enhancement of the hypocholesterolemic activity as the length of the chain is decreased. Theoretical conformationa l and electrostatic potential analyses of 1 and olefins 10 suggest unfavora ble steric interactions in the bulky superior sidechain homologues as the d eactivating biological effect.