title: Stopped-Flow Enantioselective HPLC-CD Analysis and TD-DFT Stereochemical Characterization of Methyl Trans-3-(3,4-Dimethoxyphenyl)Glycidate.
abstract: Caffeic acid-derived polyethers are a class of natural products isolated from the root extracts of comfrey and bugloss, which are endowed with intriguing pharmacological properties as anticancer agents. The synthesis of new polyether derivatives is achieved through ring-opening polymerization of chiral 2,3-disubstituted oxiranes, whose absolute configurations define the overall stereochemistry of the produced polymer. The absolute stereochemistry of one of these building blocks, methyl trans-3-(3,4-dimethoxy-phenyl)glycidate (3), was therefore characterized by the combination of enantioselective high-performance liquid chromatography (HPLC), electronic circular dichroism (ECD) spectroscopy, and time-dependent density functional theory (TD-DFT) calculations. Initial efforts aiming at the isolation of enantiomers by means of a standard preparative HPLC protocol followed by offline ECD analysis failed due to unexpected degradation of the samples after collection. The stopped-flow HPLC-CD approach, by which the ECD spectra of enantiomers are measured online with the HPLC system, was applied to overcome this issue and allowed a fast, reliable, and chemical-saving analysis, while avoiding the risks of sample degradation during the collection and processing of enantiomeric fractions. Subsequent TD-DFT calculations identified ( as the first eluted enantiomeric fraction on the Lux Cellulose-2 column, therefore achieving a full stereochemical characterization of the chiral oxirane under investigation.
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Tedesco
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Fabini
authors.affiliation: Kutateladze Institute of Pharmacochemistry, Tbilisi State Medical University, Tbilisi, Georgia.
authors.forename: Vakhtang
authors.initials: V
authors.lastname: Barbakadze
authors.affiliation: Kutateladze Institute of Pharmacochemistry, Tbilisi State Medical University, Tbilisi, Georgia.
authors.forename: Maia
authors.initials: M
authors.lastname: Merlani
authors.affiliation: Department of Chemistry and Biology, University of Salerno, Fisciano, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Zanasi
authors.affiliation: Institute of Physical and Analytical Chemistry, School of Exact and Natural Sciences, Tbilisi State University, Tbilisi, Georgia.
authors.forename: Bezhan
authors.initials: B
authors.lastname: Chankvetadze
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Bertucci
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D002942:Circular Dichroism / Q000379:methods*; D004852:Epoxy Compounds / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet / Q000379:methods; D013237:Stereoisomerism
chemical_list: D004852:Epoxy Compounds
keywords: absolute configuration; chiroptical spectroscopy; enantioseparation; hyphenated HPLC; oxiranes; polyethers; quantum chemistry; stereochemistry