DESIGN AND SYNTHESIS OF SQUALENE SYNTHASE INHIBITORS - ACYCLIC MIMICSOF THE ZARAGOZIC ACIDS

A simple and versatile synthetic scheme employing D-malic acid as the principal building block permits the ready preparation of acyclic mimi cs of the squalene synthase inhibitor zaragozic acid A (ZA-A). Several compounds which were synthesized according to this approach have rat liver squalene synthase (RLSS) enzyme activities ranging from 200 to 4 70 nM, as compared to 0.3 nM for ZA-A. These analogs represent the fir st examples in this series which possess biological activity.