Work

Determination of the Preferred Stereoisomer of Natural Product Bisabolol in Chloroform Solution through Quantum Chemical Calculations of 1 H NMR Chemical Shifts

Year: 2025

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide The elucidation of natural product structures and the differentiation of stereoisomers are important issues in organic chemistry. An example is the sesquiterpene (−)-α-bisabolol (αBis), having two stereogenic centers, αBis and a flexible side chain that generates high conformational freedom. Recently, new tools named DP4+ and ANN-PRA, which are probabilistic approaches, were used in combination to solve the relative configuration of αBis (α and epi-α diastereomers). Nuclear magnetic resonance (NMR) chemical shifts obtained from density functional theory (DFT) calculations in the vacuum were used by the DP4+ and ANN-PRA computational algorithms averaged by the Boltzmann population. Although such a procedure can provide an indication of the most probable enantiomer, no information on the spatial arrangement of the preferred molecular structure present in the NMR experiment (in CDCl 3 ) could be obtained. In this work, we used the DFT methodology and the polarizable continuum model approach, with the inclusion of explicit CHCl 3 solvent molecules, to calculate 1 H NMR spectra for various distinct trial molecular structures of αBis, encompassing α and epimeric forms, varying relevant torsion angles to find plausible minimum energy structures on the potential energy surface, including solvent effects. Through comparison between the experimental and theoretical 1 H NMR profiles in chloroform solution, we were able to unambiguously elucidate the predominant molecular structure (enantiomer α) that reproduced faithfully the experimental 1 H NMR pattern. This could not be done in previous work employing the DP4+ and ANN-PRA tools; however, there is an agreement that the α stereoisomer should be predominant. The preferred α-Bis molecular structure reported here will most probably interact with biological targets.

Source: ACS Omega

DOI: 10.1021/acsomega.5c07923

Authors: Haroldo C. Da Silva, Lucas H. Martorano, Fernando M. Dos Santos, Wagner B. De Almeida

Institutions: Universidade Federal Fluminense, Universidade do Estado do Rio de Janeiro

Language: English

Topic: Molecular spectroscopy and chirality

Subfield: Spectroscopy

Field: Chemistry

Domain: Physical Sciences

Open Access status: gold

Estimated APC paid: $1,935

Funders: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro