Separation, conformation in solution and absolute configuration of ethopropazine enantiomers

Enantiomer. 2002 Mar-Jun;7(2-3):149-56. doi: 10.1080/10242430212188.

Abstract

Enantiomers of ethopropazine x HCl (10-(2-diethylaminopropyl)phenothiazine hydrochloride) were prepared by fractional crystallization of diastereomeric dibenzoyltartaric acid salts, and their optical purity (enantiomeric excess, ee) determined by HPLC on Chiralcel OJ column. With a solvent mixture n-hexane/t-butanol/triethylamine (100:3:0.5) as eluent a very good enantioseparation (alpha = 1.68) for racemic ethopropazine was obtained. Enantiomeric purity for (-)-enantiomer was 99.1% and for (+)-enantiomer 97.9%. Combined data from NMR and CD spectra of both enantiomers, along with previously reported X-ray structure analyses of racemic ethopropazine, revealed skewed conformation of tricyclic system in solution, and (S)-configuration on the stereogenic center for (-)-enantiomer, and (R)-configuration for (+)-enantiomer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antipsychotic Agents / chemistry
  • Antipsychotic Agents / isolation & purification*
  • Chromatography, High Pressure Liquid
  • Circular Dichroism
  • Magnetic Resonance Spectroscopy
  • Molecular Conformation
  • Optical Rotation
  • Phenothiazines / chemistry
  • Phenothiazines / isolation & purification*
  • Stereoisomerism

Substances

  • Antipsychotic Agents
  • Phenothiazines
  • profenamine