Stereochemistry (and Conformation) of Nucleosides and Their Synthetic Precursors by Vibrational Circular Dichroism

Abstract

The chemistry of artificial nucleosides is associated with the difficulties in the characterization of the stereochemistry and conformation of their furanose ring moiety. This unit describes how to use vibrational circular dichroism (VCD) spectroscopy to identify the three-dimensional structure of nucleosides. The experimental part of this protocol is dedicated to obtain a VCD spectrum of a sample with high S/N ratio. The computational part generally starts with a conformational search using molecular mechanics and the following structural optimization by density functional theory calculation. Then, theoretical VCD spectra of stable conformers are calculated and averaged on the basis of their Boltzmann population. Finally, the obtained experimental and theoretical VCD spectra are compared qualitatively or quantitatively. The agreement between these spectra leads to determination of the stereochemistry of the studied molecule. This protocol may also be useful for analyzing the conformation of nucleosides. © 2018 by John Wiley & Sons, Inc.