Resolution, Absolute Configuration and Cholinergic Enantioselectivity of (+) and (-) cis-2-Methyl-5-dimethylaminomethyl-1,3-oxathiolane Methiodide.

The potent cholinergic agonist (i)-cis-2-methyl-5-[(dimethylamino)methyl]-1,3-oxathiolamnee thiodide [ (+l] wasresolved into enantiomeric forms. Their absolute configurations were established by a synthetic pathway that alsoallowed the synthesis of the corresponding diastereomeric (+)- and (-)-trans-2-methyl-5-[(dimethylamino)-methyl]-l,3-oxathiolane methiodide [(+)- and (-)-lo]. Compound (+)-lw, hich is the most potent of the four isomers,showed the same absolute configuration as L-(+)-muscarine and (+)-cis-dioxolane. The four isomers were testedon guinea pig ileum and frog rectus abdominis, and their muscarinic and nicotinic potency (EPMR) and selectivitywere determined. The relationships between stereoisomerism and potency are discussed.