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 subjected to a study of structure-activity relationship. For most of the prepared derivatives, either with a carbonyl (8a-8e), a hydroxy group (9a-9e), or with a conjugated double bond (10a-10d), significant effects on serum lipoprotein cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides were displayed. The results showed an enhancement of the hypocholesterolemic activity as the length of the chain is decreased. Theoretical conformational and electrostatic potential analyses of I and olefins 10 suggest unfavorable steric interactions in the bulky superior side-chain homologues as the deactivating biological effect.