SYNTHESIS OF C3 HETEROATOM-SUBSTITUTED AZETIDINONES THAT DISPLAY POTENT CHOLESTEROL ABSORPTION INHIBITORY ACTIVITY

The C3 phenylpropyl side chain of N-phenylazetidinones related to SCH 56524 was modified by replacing the hydroxymethylene with various isoe lectronic or isosteric groups. Modifications at the 3' position led to less-active compounds; however, modifications at the 1' position prov ided compounds with improved cholesterol absorption inhibitory activit y. An enantioselective route for the synthesis of C3 1'-sulfur-substit uted azetidinones and the development of structure-activity relationsh ips for this series of compounds are presented.