Stopped‐Flow Enantioselective HPLC‐CD Analysis and TD‐DFT Stereochemical Characterization of Methyl Trans‐3‐(3, 4‐Dimethoxyphenyl)Glycidate. Issue 12 (8th October 2015)

• Record Type: Journal Article
• Authors: Tedesco, Daniele; Fabini, Edoardo; Barbakadze, Vakhtang; Merlani, Maia; Zanasi, Riccardo; Chankvetadze, Bezhan; Bertucci, Carlo
• Is Part Of: Chirality. Volume 27:Issue 12(2015)
• Page Start: 914
• Page End: 918
• Publication Date: 2015-10-08
• Subjects: oxiranes -- polyethers -- absolute configuration -- stereochemistry -- enantioseparation -- hyphenated HPLC -- chiroptical spectroscopy -- quantum chemistry; Chirality -- Periodicals; Pharmaceutical chemistry -- Periodicals; 541.22
• DOI: 10.1002/chir.22539
• Languages: English
• ISSNs: 0899-0042

Abstract

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‐openingpolymerization of chiral 2, 3‐disubstituted oxiranes, whose absolute configurations define the overall stereochemistry of the produced polymer. The absolute stereochemistry of one of thesebuilding blocks, methyl trans ‐3‐(3, 4‐dimethoxy‐phenyl)glycidate (3 ), was therefore characterized by the combination ofenantioselective high‐performanceliquid 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 ((2S, 3R)-3 as the first eluted enantiomeric fraction on the Lux Cellulose‐2 column, therefore achieving a full stereochemical characterization of the chiral oxirane under investigation. Chirality 27:914–918, 2015 . © 2015 Wiley Periodicals, Inc. Abstract : The absolute stereochemistry of methyl trans ‐3‐(3, 4‐dimethoxyphenyl)glycidate (3 ) was 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. The stopped‐flow HPLC‐CD approach, by which the ECD spectra of enantiomers are measured on‐line with the HPLC system, allowed a fast, reliable and chemical‐saving analysis, while avoiding the risks of sample degradation.