Deuterium effects on the vibrational circular dichroism spectra of flavanone

Abstract

The minimum chemical modification that can be incorporated into an organic molecule is the replacement of a hydrogen atom for a deuterium atom. This change is not altering the pharmacological properties of a molecule, although it provides the possibility of making specific spectroscopic evaluations. Thus, in the present study, we explore how a stereogenic center is influenced by such an isotopic labeling. The studies were conducted on both enantiomers of flavanone (1 and 2) which is the parent molecule of a large group of pharmacologically active natural occurring secondary metabolites. Flavanone comprised 12 carbon atoms forming two benzene rings, a carbonyl group, an ethereal oxygen atom, a methylene group, and only one C–H stereogenic center, so it seems to be an ideal candidate for such studies. Density functional theory (DFT) calculations were used for the accurate prediction of vibrational circular dichroism (VCD) spectra of (R)‐(3) and (S)‐flavanone‐2‐d (4), of (R)‐(5) and (S)‐flavanone‐3,3‐d2 (6), and of (R)‐(7) and (S)‐flavanone‐2′,3′,4′,5′,6′‐d5 (8). To gain compounds that provide experimental VCD spectra for comparative purposes, the calculated spectra of both enantiomers of the corresponding flavanones, obtained after HPLC separation of the racemates by means of a chiral column, were contrasted, thereby revealing excellent agreements when using the CompareVOA software. In addition, the VCD spectra of both unlabeled enantiomeric flavanones (1 and 2) were also compared to the labeled molecules, revealing that the VCD spectra show significant variations induced by the deuterium incorporation.

Vibrational Circular Dichroism Study of Pipitzols and of Their Inverse Epimer Constituents α- and β-Pipitzol

“…However, there was no VCD spectral change observed in the 1800-950 cm −1 region induced by the newly generated C-8 stereogenic center. This is in severe contrast with the results obtained for deuterated flavanones 29 in which spectacular spectral changes were generated.…”