Synthesis, NMR spectroscopy study, and antimuscarinic activity of a series of 2-(Acyloxymethyl)-1,3-dioxolanes

Abstract

A series of 1,3-dioxolane-based ligands, bearing hydroxymethyl or ester functionalities, was synthesized and tested as potential muscarinic antagonists. The compounds display moderate to low affinity for the three receptor subtypes M 1-M 3, with some of them showing a significant selectivity for the M 3 subtype. The configurational and conformational properties were studied using NOE experiments and vicinal coupling constants. The 1H and 13C NMR chemical shifts show stereochemically dependent trends. Quantitative analysis of conformer populations showed that the exocyclic CH 2N +(CH 3) 3 group is prevalently in a pseudo-axial orientation in the cis isomers and in a pseudo-equatorial orientation in the trans isomers.