N-Substitution effects on the conformations of iminosugar analogues of 1-deoxy-l-idose and 1-deoxy-l-iduronic acid

Abstract

We herein report the synthesis and complete conformational analysis of a focused library of iminosugar analogues of L-idose and L-iduronic acid designed to probe the impact of N-substitution on ring dynamics. Molecular modelling, supported by experimental ¹H NMR data, reveals that introducing alkyl or acyl substituents on the ring nitrogen profoundly alters the conformational equilibrium, inducing a clear shift from the preferred ¹C₄ chair to the ⁴C₁ conformation. These findings highlight how targeted nitrogen functionalisation can be used to modulate the conformational landscape of iminosugars, offering new opportunities for the rational design of glycomimetic scaffolds.