Synthesis of Aristoquinoline Enantiomers and Their Evaluation at the α3β4 Nicotinic Acetylcholine Receptor

Organic Letters
2021.0

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 alpha 3 beta 4 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.

Knowledge Graph

Similar Paper

Synthesis of Aristoquinoline Enantiomers and Their Evaluation at the α3β4 Nicotinic Acetylcholine Receptor
Organic Letters 2021.0
Alkaloids Purified from <i>Aristotelia chilensis</i> Inhibit the Human α3β4 Nicotinic Acetylcholine Receptor with Higher Potencies Compared with the Human α4β2 and α7 Subtypes
Journal of Natural Products 2019.0
Tying up Nicotine: New Selective Competitive Antagonist of the Neuronal Nicotinic Acetylcholine Receptors
ACS Medicinal Chemistry Letters 2015.0
Synthesis and Pharmacological Characterization of Nicotinic Acetylcholine Receptor Properties of (+)- and (−)-Pyrido-[3,4-b]homotropanes
Journal of Medicinal Chemistry 2006.0
Design, Synthesis, and Biological Evaluation of Erythrina Alkaloid Analogues as Neuronal Nicotinic Acetylcholine Receptor Antagonists
Journal of Medicinal Chemistry 2013.0
Synthesis, Determination of the Absolute Stereochemistry, and Evaluations at the Nicotinic Acetylcholine Receptors of a Hydroxyindolizidine Alkaloid from the Ant Myrmicaria melanogaster
HETEROCYCLES 2009.0
Dual Nicotinic Acetylcholine Receptor α4β2 Antagonists/α7 Agonists: Synthesis, Docking Studies, and Pharmacological Evaluation of Tetrahydroisoquinolines and Tetrahydroisoquinolinium Salts
Journal of Medicinal Chemistry 2018.0
Synthesis and evaluation of nuciferine and roemerine enantiomers as 5-HT<sub>2</sub>and α<sub>1</sub>receptor antagonists
MedChemComm 2018.0
Synthesis, optical resolution, absolute configuration, and preliminary pharmacology of (+)- and (-)-cis-2,3,3a,4,5,9b-hexahydro-1-methyl-1H-pyrrolo[3,2-h]isoquinoline, a structural analog of nicotine
Journal of Medicinal Chemistry 1993.0
Molecular requirements of the recognition site of cholinergic receptors. 22. Resolution, absolute configuration, and cholinergic enantioselectivity of (+)- and (-)-cis-2-methyl-5-[(dimethylamino)methyl]-1,3-oxathiolane methiodide
Journal of Medicinal Chemistry 1986.0