Antiphlogistic aryloxypropionic acids: configurational study.

Abstract

Configurational relationships of a series of antiphlogistic 2-aryloxypropionyl derivatives by means of 1H-NMR and HPLC methods were demonstrated. NMR spectra of racemic mixtures and optically active esters were recorded by adding suitable quantities of Eu(hfc)3 chiral shift reagent. The chemical shift values of the non-equivalent signals were unambiguously assigned to R and S enantiomers and the sign of the delta delta parameter was shown to be the same for all compounds. Chiral resolution of (1-naphthyl)methylamides on R-DNBPG and S-DNBL analytical columns was carried out. The alpha and K' values of the chromatographic separations by means of S-DNBL phase were generally better than those using R-DNBPG. The elution order could be determined: S isomers are generally eluted last from both columns. For all compounds the solute-CSP interaction was studied by molecular models to verify if the interacting conformation is the same for the enantiomers which have equal configuration. This control is essential to validate the configurational assignment method by means of HPLC analysis. Finally, we hypothesized the interactions of the compounds showing inversion of the elution order or lack of chiral resolution.