Title
Absolute configuration assignment of caffeic acid ester derivatives from Tithonia diversifolia by vibrational circular dichroism: the pitfalls of deuteration
Author
Gari V. Ccana-Ccapatinta, Bruno L. Sampaio, Fernando M. dos Santos Jr., João M. Batista Jr., Fernando B. Da Costa
Year
2017
Journal
Tetrahedron: Assymetry
Abstract
Recently, it was observed that infrared (IR) and vibrational circular dichroism (VCD) calculations including deuterated hydroxyl groups in phenolic and saccharide moieties improved significantly the agreement with experimental data obtained in methanol-d4. In the present study, the relative and absolute configurations of three methanol-soluble caffeic acid ester derivatives 1–3, isolated from Tithonia diversifolia, were established by a combined use of experimental and calculated 13C NMR chemical shifts, as well as electronic circular dichroism (ECD) and VCD spectroscopies. Interestingly, the attempt to reproduce the deuteration pattern arising from possible isotopic exchange in methanol-d4 solution led to nearly mirror image calculated VCD spectra for 1 when compared to the non-deuterated molecule with the same absolute configuration. This latter fact can potentially lead to absolute configuration misassignments. A closer inspection of the vibrational chiroptical properties of 1revealed that the deuteration status of the tertiary hydroxyl group at C-2 is critical for the correct reproduction of experimental VCD data in protic solvents. Therefore, in the case of stereochemical analysis of polar chiral natural product molecules, a combination of VCD and ECD is recommended.
Instrument
J-815
Keywords
Circular dichroism, Absolute configuration, Cotton effect, Pharmaceutical