Syntheses of (S)-(+)-trihexyphenidyl hydrochloride and (S)-(+)-procyclidine hydrochloride, two anticholinergics, using (S)-(-)-3-cyclohexyl-3-hydroxy-3-phenylpropanoic acid as chiral synthon.
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.
Schjelderup
L
L
Department of Chemistry, Agricultural University of Norway, Oslo.
Harbitz
O
O
Groth
P
P
Aasen
A J
AJ
D002942:Circular Dichroism; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009904:Optical Rotation; D010666:Phenylpropionates; D011352:Procyclidine / Q000138:chemical synthesis*; D011759:Pyrrolidines / Q000138:chemical synthesis*; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism; D014282:Trihexyphenidyl / Q000138:chemical synthesis*
D007202:Indicators and Reagents; D010666:Phenylpropionates; D011759:Pyrrolidines; D014282:Trihexyphenidyl; C054071:3-cyclohexyl-3-hydroxy-3-phenylpropanoic acid; D011352:Procyclidine