Synthesis of Aristoquinoline Enantiomers and Their Evaluation at the α3β4 Nicotinic Acetylcholine Receptor
Malaika D. Argade, Carolyn J. Straub, Lisa E. Rusali, Bernard D. Santarsiero, Andrew P. Riley
Abstract
The first synthesis of aristoquinoline (1), a naturally occurring nicotinic acetylcholine receptor (nAChR) antagonist, was accomplished using two different approaches. Comparison of the synthetic material’s spectroscopic data to that of the isolated alkaloid identified a previously misassigned stereogenic center. An evaluation of each enantiomer’s activity at the α3β4 nAChR revealed that (+)-1 is significantly more potent than (−)-1. This unexpected finding suggests that naturally occurring 1 possesses the opposite absolute configuration from indole-containing Aristotelia alkaloids.
Topics & Concepts
ChemistryEnantiomerAcetylcholine receptorNicotinic agonistAcetylcholineNicotinic acetylcholine receptorReceptorPharmacologyMuscarinic acetylcholine receptor M5Alpha-4 beta-2 nicotinic receptorStereochemistryMuscarinic acetylcholine receptor M3BiochemistryMedicineAnalytical Chemistry and ChromatographyMolecular spectroscopy and chiralityChemical synthesis and alkaloids