Syntheses of (S)-(+)-Trihexyphenidyl Hydrochloride and (S)-(+)-Procyclidine Hydrochloride, two Anticholinergics, using (S)-(-)-3-Cyclohexyl-3-hydroxy-3-phenylpropanoic Acid as Chiral Synthon.

Abstract

The absolute configuration of the more active (-)-enantiomer of the anticholinergic trihexyphenidyl hydrochloride has been established as (R) by syntheses of (S)-(+)-procyclidine hydrochloride, whose absolute configuration has been established previously, and (S)-(+)-trihexyphenidyl hydrochloride from the same chiral building block, viz. (S)-(-)-cyclohexyl-3-hydroxy-3-phenylpropanoic acid. Both enantiomers of this chiral synthon were prepared by optical resolution of the corresponding racemate, employing (R)- and (S)-1-phenylethylamine, respectively, as resolving agents.