ANTICHOLINERGICS:SYNTHESIS OF α,β ISOMERS OF 3-METHYL-3-AZABICYCLO3, 3, 1 NONAN-9-YL ESTERS

A series of α-and β-isomers of 3-methyl-3-azabicyclo-3,3,1 nonan-9-yl substituted carboxylic esters were synthesized. The starting material 3methyl-3-azabicyclo 3,3,1 nonan-9-one was prepared from cyclohexanone, methylamine and formaldehyde by Mannich reaction. The ketone was reduced and separated into 9α and 9β alcohols, and the isomeric alcohols were esterified separately with various methyl carboxylates to give the corresponding esters Ⅲ_1～10. The stereochemistry of these esters were identified by means of ¹HNMR.Preliminary pharmacological results showed that, except compounds Ⅲ₉ and Ⅲ₁₀ all compounds exhibited potent central anticholinergic activities, six of them were equal to or more potent than atropine. The α and β isomers of each pair were close in their anticholinergic activity in 9α, βisomers of 3-methyl-3-azabicyclo 3,3,1 nonanyl esters.