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Synthesis and absolute configuration of the stereoisomers of [2‐(1‐diethylaminopropyl)] 1‐hydroxy‐1,1′‐bicyclohexyl‐2‐carboxylate, a muscarinic antagonist
Author(s) -
Bugno Cristina Di,
Colombani Spartaco Mauro,
Dapporto Paolo,
Garzelli Giorgio,
Giorgi Raffaello,
Paoli Paola,
Subissi Alessandro,
Turbanti Luigi
Publication year - 1997
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/(sici)1520-636x(1997)9:8<713::aid-chir1>3.0.co;2-6
Subject(s) - chemistry , absolute configuration , stereochemistry , chirality (physics) , carboxylate , stereospecificity , cyclohexane , molecule , stereoisomerism , cis–trans isomerism , organic chemistry , catalysis , chiral symmetry breaking , physics , quantum mechanics , nambu–jona lasinio model , quark
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 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‐[1,1′‐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.