Title
The Role of Chirality in a Set of Key Intermediates of Pharmaceutical Interest, 3-aryl-substituted-γ-butyrolactones, evidenced by Chiral HPLC Separation and by Chiroptical Spectroscopies
Author
Daniela Rossi, Rita Nasti, Simona Collina, Giuseppe Mazzeo, Simone Ghidinelli, Giovanna Longhi, Maurizio Memo, Sergio Abbate
Year
2017
Journal
Journal of Pharmaceutical and Biomedical Analysis
Abstract
The enantiomers of four chiral 3-aryl-substituted-γ-butyrolactones, key intermediates for the preparation of compounds of pharmaceutical interest, were successfully isolated by enantioselective chromatography, employing the Chiralpak AD-H chiral stationary phase. For all compounds the same elution order was observed, as monitored by a full set of chiroptical methods that we employed, namely ORD (optical rotatory dispersion), ECD (electronic circular dichroism, or CD in the UV range), and VCD (vibrational circular dichroism, or CD in the IR range). By density functional theory (DFT) calculations we were able to determine that the first eluted enantiomer has (S) absolute configuration in all four cases. We were able to justify the elution order by molecular docking calculations for all four enantiomeric pairs and suitable modeling of the stationary and mobile phases of the employed columns. The optimal performance of the chiroptical spectroscopies and of the DFT calculations allows us to formulate a lactone chirality rule out of the Cdouble bond; length as m-dashO stretching region of the VCD spectra.
Instrument
J-815
Keywords
Circular dichroism, Absolute configuration, Pharmaceutical