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

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 LH and C-13 NMR chemical shifts show stereochemically dependent trends. Quantitative analysis of conformer populations showed that the exocyclic CH2N+(CH3)(3) group is prevalently in a pseudo-axial orientation in the cis isomers and in a pseudo-equatorial orientation in the trans isomers. Copyright (C) 1996 Elsevier Science Ltd