Enantioselective high-performance liquid chromatography combined with spectroscopic methods and theoretical calculations: A valid strategy to determine the absolute configuration of eugenol derivatives

Simone Manetto; Giulia Mazzoccanti; Gaia Pulitelli; Sofia Niccolai; Damiano Tanini; Marco Pierini; Roberto Cirilli

doi:10.1002/chir.23668

Enantioselective high-performance liquid chromatography combined with spectroscopic methods and theoretical calculations: A valid strategy to determine the absolute configuration of eugenol derivatives

Chirality. 2024 May;36(5):e23668. doi: 10.1002/chir.23668.

Authors

Simone Manetto¹, Giulia Mazzoccanti¹, Gaia Pulitelli², Sofia Niccolai³, Damiano Tanini³, Marco Pierini¹, Roberto Cirilli²

Affiliations

¹ Department of Drug Chemistry and Technology, "Sapienza" University of Rome, Rome, Italy.
² National Centre for the Control and Evaluation of Medicines, Istituto Superiore di Sanità, Rome, Italy.
³ Department of Chemistry "Ugo Schiff", University of Florence, Sesto Fiorentino, Italy.

PMID: 38747133
DOI: 10.1002/chir.23668

Abstract

The absolute configuration of three chiral eugenol derivatives was assigned by a multi-step methodology based on enantioselective HPLC combined with spectroscopic and theoretical calculations. Milligram amounts of enantiopure forms used for stereochemical characterization were isolated by HPLC on the immobilized amylose-based chiral stationary phase Chiralpak IG using normal phase elution conditions. The absolute configuration was indirectly determined for one of the three compounds by ¹H NMR via methoxy-α-trifluoromethyl-α-phenylacetic acid derivatization (Mosher's acid). Comparison of the experimental and predicted electronic circular dichroism spectra confirmed the stereochemical assignment by Mosher's method and extended the absolute configuration assignment to two other chiral compounds.

Keywords: 1H Mosher method; Chiralpak IG; absolute configuration; electronic circular dichroism; eugenol derivatives; theoretical calculations.