Chiral recognition model for the resolution of ephedrine and related α,β-aminoalcohols as enantiomeric oxazolidine derivatives

• Published in: Journal of Chromatography A 1986, Vol.355 (1), p.149-156
• Main Authors: Wainer, Irving W., Doyle, Thomas D., Fry, Fred S., Hamidzadeh, Zohreh
• Format: Article
• Language: English
• Subjects: Alcaloids; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Heterocyclic compounds, pigments; Other biological molecules
• ISSN: 0021-9673
• DOI: 10.1016/S0021-9673(01)97311-X

The mechanism of chiral recognition has been investigated for a series of enantiomeric cis-oxazolidines on a commercially available high-performance liquid chromatographic chiral stationary phase (HPLC-CSP). The oxazolidine molecules were synthesized through the condensation of ephedrine and ephedrine-related molecules with aromatic aldehydes. The resulting molecules are rigid five-membered rings whose configuration has been determined by proton magnetic resonance and single-crystal X-ray diffraction. The oxazolidines derived from the condensation of ephedrine and aldehydes containing a p-basic moiety such as naphthaldehyde were resolved on the HPLC-CSP as were those oxazolidines synthesized by using a p-acidic aldehyde such as p-nitrobenzaldehyde. However, there was a reversal in the elution order for the two types of oxazolidines. Oxazolidines resulting from the condensation of ephedrine and a p-neutral aldehyde such as benzaldehyde were not resolved. The results of this study suggest a chiral recognition model based on the formation of diastereomeric solute-CSP complexes through a single attractive interaction and chiral discrimination resulting from the difference in steric fit.