Synthesis and absolute configuration of the stereoisomers of [2-(1-diethylaminopropyl)] 1-hydroxy-1,1′-bicyclohexyl-2-carboxylate, a muscarinic antagonist

✍ Scribed by Cristina Di Bugno; Spartaco Mauro Colombani; Paolo Dapporto; Giorgio Garzelli; Raffaello Giorgi; Paola Paoli; Alessandro Subissi; Luigi Turbanti

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 175 KB
• Volume: 9
• Category: Article
• ISSN: 0899-0042
• DOI: 10.1002/(sici)1520-636x(1997)9:8<713::aid-chir1>3.0.co;2-6

✦ Synopsis

The compound [2-(1-diethylaminopropyl)] 1-hydroxy-1,1Ј-bicyclohexyl-2-carboxylate 1 is a muscarinic antagonist characterized by the presence of three chiral atoms and eight possible stereoisomers. The binding affinities to the five cloned m 1 -m 5 muscarinic receptors of the stereoisomers of 1 were previously investigated and proved to be related to the chirality of the molecules. The eight isomers are prepared through the synthesis of their racemates followed by chemical resolution as (+) and (-) tartrate or (+) and (-) dibenzoyltartrate salts. The isomers with cis-configuration of OH and COOH substituents of the cyclohexane are also obtained by coupling optically active (1S, 2S) or (1R,2R)-1-hydroxy-[1,1Ј-bicyclohexyl]-2-carboxylic acid with (S)-or (R)-1diethylamino-2-propanol. Chiral GC and HPLC methods are used to determine their optical purity. The absolute configurations of the four cis-and four trans-isomers are established by stereospecific synthesis and X-ray crystallographic data. Chirality 9: 713-721, 1997.