Determination of Complex Small-Molecule Structures Using Molecular Alignment Simulation.

Alain Ibáñez De Opakua,Ikenna E Ndukwe,Gary E Martin,Markus Zweckstetter,R Thomas Williamson,Frederik Klama

doi:10.1002/anie.202000311

Abstract

Correct structural assignment of small molecules and natural products is critical for drug discovery and organic chemistry. Anisotropy‐based NMR spectroscopy is a powerful tool for the structural assignment of organic molecules, but it relies on the utilization of a medium that disrupts the isotropic motion of molecules in organic solvents. Here, we establish a quantitative correlation between the atomic structure of the alignment medium, the molecular structure of the small molecule, and molecule‐specific anisotropic NMR parameters. The quantitative correlation uses an accurate three‐dimensional molecular alignment model that predicts residual dipolar couplings of small molecules aligned by poly(γ‐benzyl‐l‐glutamate). The technique facilitates reliable determination of the correct stereoisomer and enables unequivocal, rapid determination of complex molecular structures from extremely sparse NMR data.

Highlights

Alain IbμÇez de Opakua, Frederik Klama, Ikenna E
Anisotropy-based NMR spectroscopy is a powerful tool for the structural assignment of organic molecules, but it relies on the utilization of a medium that disrupts the isotropic motion of molecules in organic solvents
We establish a quantitative correlation between the atomic structure of the alignment medium, the molecular structure of the small molecule, and molecule-specific anisotropic NMR parameters

Summary

Introduction

Alain IbμÇez de Opakua, Frederik Klama, Ikenna E. We describe a molecular alignment simulation that accurately predicts RDCs in small molecules dissolved in organic solvents from the three-dimensional structure of the alignment medium.

Results

Conclusion