Computational Approaches and Use of Chiroptical Probes in the Absolute Configuration Assignment to Natural Products by ECD Spectroscopy: A 1,2,3-Trihydroxy-p-menthane as a Case Study.

Giulia Marsico,Antonio Evidente,Patrizia Scafato,Sandra Belviso,Umberto Calice,Stefano Superchi

doi:10.3390/biom12030421

Abstract

In this study, the computational analysis of electronic circular dichroism (ECD) spectra and the employment of biphenyl chiroptical probes were compared in the absolute configuration assignment of (-)-1α,2α,3β-trihydroxy-p-menthane (1), taken as a representative example of a UV-transparent chiral natural product. The usefulness of chiroptical probes in the configurational assignments of natural products and their complementarity to the computational protocols is herein highlighted. The biphenyl probe approach proves to be straightforward, reliable, and suitable for conformationally mobile and ECD silent compounds, not treatable by computational analysis of chiroptical data.

Highlights

Academic Editor: ZofiaThe assignment of absolute configuration (AC) is a fundamental task to be addressed in the structural characterization of chiral compounds, including natural products
AC assignment to triol (-)-1 was attempted by comparison of the experimental and the TDDFT-computed electronic circular dichroism (ECD) spectra, following a reliable and straightforward approach employed for a number of chiral compounds [54], including natural products [55,56]
20 conformers, accounting for 87% of the overall population, displayed the isopropyl group at C-4 in an equatorial position and an axial methyl at C-1

Summary

Introduction

Academic Editor: ZofiaThe assignment of absolute configuration (AC) is a fundamental task to be addressed in the structural characterization of chiral compounds, including natural products. The key role of AC on the bioactivity of naturally occurring chiral metabolites [1,2], agrochemicals [3], or drugs [4,5] has been clearly established. Natural products are often available in tiny amounts and/or in non-crystalline form, i.e., features that prevent a direct assignment of AC by X-ray diffraction analysis [8]. For these compounds, the spectroscopic methods based on nuclear magnetic resonance (NMR) and chiroptical spectroscopy provide powerful tools for the AC assignment, allowing the treatment of molecules in solution.

Methods

Results

Conclusion