Vibrational Circular Dichroism Discrimination of Diastereomeric Cedranol Acetates

Abstract

The reliability of vibrational circular dichroism (VCD) spectroscopy to discriminate four diastereomeric cedranol acetates 1-4 by means of their absolute configuration is examined. The usage of CompareVOA software to quantify comparisons of the measured infrared (IR) and VCD spectra with the corresponding simulated spectra at the B3LYP/DGDZVP and B3PW91/DGDZVP levels of theory for each diastereomer enabled the B3PW91 functional to be qualified as superior to the B3LYP functional for vibrational calculations of 1-4. Analogously, a set of quantitative VCD spectra cross-comparisons of 1-4 unambiguously distinguished the diastereomers using B3PW91 and failed using B3LYP. Remarkably, quantitative IR spectra cross-comparisons of 1-4 using B3PW91 or B3LYP functionals demonstrated that the achiral spectroscopic IR technique is not able to distinguish cedranol acetate diastereomers. VCD comparisons using anisotropy g-factor values of bands in the 1550-950 cm(-1) region of the spectra were of aid to facilitate visual spectra matching for each diastereomer.

Recent advances in the use of vibrational chiroptical spectroscopic methods for stereochemical characterization of natural products

“…145 The absolute conguration of (À)-stypotriol (118) isolated from Stypopodium zonale was determined as 3S,5R,8R,9R,10S,13S,14S using VCD and B3LYP/DGDZVP predicted spectra for the triacetate derivative. Novofumigatonin (117), a new orthoester meroterpenoid isolated from Aspergillus novofumigatus had its relative stereogeometry established by NMR and X-ray analysis.…”

“…This molecule was assigned as 5S,7S,8R,9R,10S,17S,5 0 S,7 0 S,8 0 R,9 0 R,10 0 S,17 0 S. The absolute conguration of the rare isoneoamphilectane carbon skeleton, present in marine diterpenes isolated from the sponge Svenzea ava, was determined using VCD and DFT [B3LYP/6-31G(d)] calculations 117. VCD spectroscopy in combination with DFT calculations (B3PW91/DGDZVP) was able to reliably discriminate four diastereomeric cedrol-related tricyclic sesquiterpenes: cedranol (69), neoisocedranol(70), neocedranol(71), and isocedranol(72) 118. VCD spectroscopy in combination with DFT calculations (B3PW91/DGDZVP) was able to reliably discriminate four diastereomeric cedrol-related tricyclic sesquiterpenes: cedranol (69), neoisocedranol(70), neocedranol(71), and isocedranol(72) 118.…”

Comparison of Experimental and Calculated Chiroptical Spectra for Chiral Molecular Structure Determination

“…The possibility of using ESI approach to ROA spectra was indicated, but applications to ROA were not reported to date. A commercial software, Compare VOA , that uses this ESI approach for VCD is being widely used by Joseph‐Nathan and coworkers …”

Enantiomeric 4‐Acylamino‐6‐alkyloxy‐2 Alkylthiopyrimidines As Potential A3Adenosine Receptor Antagonists: HPLC Chiral Resolution and Absolute Configuration Assignment by a Full Set of Chiroptical Spectroscopy

“…Thus, optical rotatory dispersion (ORD), electronic circular dichroism (ECD), and vibrational circular dichroism (VCD) spectra were recorded and compared to the calculated ones. The combined use of the three techniques is particularly advised for the AC assigned of flexible molecules, like drugs and natural products, which had been treated previously by the use of separate forms of chiroptical methods . Overall, this article describes the work carried out to separate the enantiomeric couples for 1 , 2 , 3 and to assign their absolute configurations in order to understand how chirality may influence their interaction with human A 3 AR.…”