SYNTHESIS AND MUSCARINIC ACTIVITY OF THE CHIRAL FORMS OF METHYLENEMUSCARONES

The synthesis of the two pairs of enantiomers of methylenemuscarones 3 and 4 has been accomplished by using (R)- and (S)-lactic esters as st arting materials. Due to the existence of different muscarinic recepto r subtypes, the compounds were examined for their ability to bind memb ranes from cerebral cortex (M1), heart (M2), and salivary glands (M3) and were assayed in ''in vitro'' functional tests as well. The results of such an investigation put in evidence that, in both binding and fu nctional tests, (-)-3 (2S,5S) and (-)-4 (2R,5S) were the eutomers and shared the stereochemistry of the eutomer of muscarone and allomuscaro ne respectively. It is worth noting that the distomer of 3 and 4 behav es as a partial agonist in the cardiac tissue and as a full agonist in the other preparations. This peculiarity of the chiral forms of 3 and 4 could account for the remarkable selectivity for the ileum observed in the corresponding racemates.