ISSN:
0899-0042
Keywords:
muscarinic antagonist
;
rociverine enantiomers
;
chiral synthesis
;
optical resolution
;
absolute configuration
;
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
The compound [2-(1-diethylaminopropyl)] 1-hydroxy-1,1′-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 m1-m5 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-[1,1′-bicyclohexyl]-2-carboxylic acid with (S)- or (R)-1-diethylamino-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. © 1997 Wiley-Liss, Inc.
Additional Material:
4 Ill.
Type of Medium:
Electronic Resource
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