Enantioselective synthesis of alpha-phosphono sulfonate squalene synthase inhibitors: chiral recognition in the interactions of an alpha-phosphono sulfonate inhibitor with squalene synthase

An enantioselective synthesis of the squalene synthase inhibitor, alpha-phosphono sulfonate triacid 1, was conducted. Deuterium incorporation investigations were performed first to determine the configurational stability of the chiral centers. Results indicated that both the triacid 1 and diester 2 were isolable as single enantiomers, whereas triester 3 was very sensitive to racemization. The method for the introduction of the asymmetric center was based on the sulfuration or alkylation of a chiral phosphorus carbanion.