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.
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 CO stretching region of the VCD spectra.
authors.affiliation: Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Rossi
authors.affiliation: Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Nasti
authors.affiliation: Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy. Electronic address: simona.collina@unipv.it.
authors.forename: Simona
authors.initials: S
authors.lastname: Collina
authors.affiliation: Dipartimento di Medicina Molecolare e Traslazionale, Università di Brescia, Viale Europa 11, 25123 Brescia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mazzeo
authors.affiliation: Dipartimento di Medicina Molecolare e Traslazionale, Università di Brescia, Viale Europa 11, 25123 Brescia, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Ghidinelli
authors.affiliation: Dipartimento di Medicina Molecolare e Traslazionale, Università di Brescia, Viale Europa 11, 25123 Brescia, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Longhi
authors.affiliation: Dipartimento di Medicina Molecolare e Traslazionale, Università di Brescia, Viale Europa 11, 25123 Brescia, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Memo
authors.affiliation: Dipartimento di Medicina Molecolare e Traslazionale, Università di Brescia, Viale Europa 11, 25123 Brescia, Italy. Electronic address: sergio.abbate@unibs.it.
authors.forename: Sergio
authors.initials: S
authors.lastname: Abbate
mesh_terms: D015107:4-Butyrolactone; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D062105:Molecular Docking Simulation; D009905:Optical Rotatory Dispersion; D004364:Pharmaceutical Preparations; D013237:Stereoisomerism
chemical_list: D004364:Pharmaceutical Preparations; D015107:4-Butyrolactone
keywords: Chiral HPLC; Lactone chirality rule; Molecular docking calculations; ORD (optical rotatory dispersion) and ECD (electronic circular dichroism); VCD (vibrational circular dichroism); γ-Butyrolactones