Vibrational Circular Dichroism: A New Tool for the Solution-State Determination of the Structure and Absolute Configuration of Chiral Natural Product Molecules

Abstract

This paper is dedicated to Professor Pedro Joseph-Nathan for his 65 th birthday. Vibrational circular dichroism (VCD) has been used in recent years to determine the absolute configuration of a number of natural product chiral molecules. In this brief review, these applications will be described and the methodology of VCD determination of absolute configuration (AC) will be explained. The principal advantages of VCD versus X-ray crystallography for absolute configuration determination are: 1) only solution-state samples are needed and therefore single crystals are not required, 2) high enantiomeric sample purity is not required, 3) high chemical purity is not required as long as impurities are not chiral and 4) solution-state conformations are obtained as an extra feature of the AC determination.

Absolute configuration of labdanes and ent-clerodanes from Chromolaena pulchella by vibrational circular dichroism

“…This task can be accomplished if a selected representative of each type of compounds is studied by vibrational circular dichroism (VCD) spectroscopy (Freedman et al, 2003). This technique, which has been recently used to determine the absolute configuration of natural products (Nafie, 2008;Cerda-García-Rojas et al, 2008;Reina et al, 2010;Muñoz et al, 2010), is based on the comparison between the experimental VCD spectrum and the corresponding theoretical curve, for the proper enantiomer, obtained by density functional theory (DFT) calculations. The calculations involve generation of weighted-averaged vibrational plots including all significantly populated conformations of the analyzed molecule.…”

Mini review: Instrumentation for vibrational circular dichroism spectroscopy, still a role for dispersive instruments

“…16,23,[25][26][27][28][29][30][31][32] These developments have resulted in the ability to accumulate data over the near IR and much of the mid-IR on a routine basis for a variety of samples, typically in solution phase. 6,7,9,31,[33][34][35][36][37][38] Subsequently, a fundamental change in the methodology came about built on the pioneering work of Nafie and co-workers 30,[39][40][41][42][43][44][45][46][47] in their development of Fourier transform based VCD instrumentation. Several labs picked up on these ideas, and modified those designs, 48-52 but the work of the Syracuse group, and its subsequent evolution to a commercial platform, has revolutionized VCD measurements and made them truly widespread.…”

Absolute configuration determination and conformational analysis of (−)‐(3S,6S)‐3α,6β‐diacetoxytropane using vibrational circular dichroism and DFT techniques

“…Furthermore, the recent simultaneous use of all these techniques for the determination of the absolute configuration of natural products has shown that VCD is the most reliable of these methodologies. 10 In this article we present the conformational analysis and absolute configuration determination of (2)-3a,6b-diacetoxytropane 1 using a combination of VCD spectroscopy, molecular mechanics, and DFT calculations. Compound 1 was prepared from (2)-6b-hydroxyhyoscyamine 2, which in turn was studied using VCD, and has been assigned the (3S,6S,3 0 S) absolute configuration.…”