Resolution, Absolute Configuration and Cholinergic Enantioselectivity of (-) and (+) c-2-Methyl-r-5-((Dimethylamino(methyl)-1,3-oxathiuolane-t-oxide Methiodide and Related Sulfones.

As a continuation of previous studies on chiral cholinergic agonists carrying a 1,3-oxathiolane nucleus, the enantiomersof c-2-methyl-r-5-[(dimethylamino)methyl]-l,3-oxathiolta-n3e-o xide methiodide ((+)- and (-)-l) and of cis-2-methyl-5-[ (dimethylamino)methyl]-1,3-oxathiolane3 ,3-dioxide ((+)- and (-)-2) were obtained and their absoluteconfigurations established by synthesis. The cholinergic potency of the four isomers was evaluated in vitro on guineapig ileum and frog rectus abdominis models, and the results show that (-)-1, which has the same absolute configurationas L-(+)-muscarine, is a selective and potent muscarinic agent. The (+)-1 enantiomer is some hundred times lesspotent than (-)-1 on the muscarinic guinea pig ileum while, on the same tissue, the corresponding sulfone derivatives((+)- and (-)-2) show no enantioselectivity.