# Redundant 15N‑Mediated J‑Couplings Reveal an Aglycone Conformation in N‑Phenyl Glycosylamines

## TL;DR

This study uses 15N-mediated J-couplings to predict the conformation of N-phenyl glycosylamines, aiding in the design of glycomimetics for drug discovery.

## Contribution

The novel use of redundant 15N-mediated J-couplings to determine aglycone conformation in N-phenyl glycosylamines.

## Key findings

- 15N-labeled N-phenyl glycosylamines were synthesized with >90% conversion in NMR tubes.
- Redundant 15N-mediated J-couplings accurately predicted aglycone conformation and nitrogen atom configuration.
- Predicted conformation of N-phenyl β-d-mannopyranosylamine matched its crystal structure.

## Abstract

Prediction of the conformation of novel N-glycomimetics
is a crucial step in their rational design for drug discovery and
glycobiology. We investigated the applicability of redundant 15N-mediated J-couplings for predicting the
aniline aglycone conformation in 15N-labeled N-phenyl glycosylamines derived from d-glucose (d-Glc), d-mannose (d-Man), d-xylose (d-Xyl), and d-lyxose (d-Lyx). The compounds
were prepared directly in an NMR tube by reacting free sugar with 15N-labeled aniline, achieving >90% conversion. The rate
of N-phenyl glycosylamine formation depended on the
concentration
of an open-chain form of the sugar in the solution. In the closed
form, the anilino substituent preferred equatorial orientation, which
dictated the anomeric ratio and influenced the pyranose ring conformation,
particularly in the case of d-Lyx and d-Xyl. The 15N label localized near the conformationally perturbed region
provided redundant 15N-mediated J-couplings
sensitive to the aniline aglycone conformation. By fitting the density
functional theory (DFT)-calculated J-couplings of
individual conformers to experimental data, we successfully predicted
both the aniline aglycone conformation and the nitrogen atom configuration.
Notably, the predicted major conformation of N-phenyl
β-d-mannopyranosylamine (6b) corresponded
to the conformer observed in the crystal structure.