Synthesis and Pharmacological Activity of gem-Dialky1-9-azabicyclo [3, 3, 1] nonane Derivatives: New Anti-Cholinergic Agent

• Published in: Chemical & pharmaceutical bulletin Vol. 20; no. 3; pp. 476 - 486
• Main Authors: YONEDA, NAOTO, ISHIHARA, TERUO, KOBAYASHI, TETSUJI, OKUMURA, KENTARO, KOJIMA, MICHIO
• Format: Journal Article
• Language: English
• Published: The Pharmaceutical Society of Japan 1972
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.20.476

6, 6-and 7, 7-dialkyl-9-alkyl-9-azabicyclo [3, 3, 1] nonan-3-one (V) and (IX), synthesized from 2, 2- and 3, 3-dialkylglutaraldehyde by the Robinson-Schöpf reaction, were reduced with NaBH4 and Na-EtOH to afford the A- and B-isomers of the corresponding 6, 6- and 7, 7-dialkyl-9-alkyl-9-azabicyclo [3, 3, 1] nonan-3-ol (VI) and (X), respectively. Hydroxy groups on 3-position of A- and B-isomer of the alcohols were confirmed to be α-and β-configuration by the formation of a tetrahydrooxazine ring, respectively. Various ester and carbamate compounds of the alcohols (VI) and (X) were synthesized and their pharmacological activities were studied. Among their compounds several glycolate derivatives had a potent anti-cholinergic activity and showed high central specificity.