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

Overview
Journal Org Lett
Publisher American Chemical Society
Specialties Biochemistry
Chemistry
Date 2021 Jul 22
PMID 34292752
Citations 4
Authors
Malaika D Argade
Carolyn J Straub
Lisa E Rusali
Bernard D Santarsiero
Andrew P Riley
Affiliations
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Abstract

The first synthesis of aristoquinoline (), 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 (+)- is significantly more potent than (-)-. This unexpected finding suggests that naturally occurring possesses the opposite absolute configuration from indole-containing alkaloids.

Citing Articles

Synthesis of α3β4 Nicotinic Acetylcholine Receptor Modulators Derived from Aristoquinoline That Reduce Reinstatement of Cocaine-Seeking Behavior.

Rusali L, Lopez-Hernandez A, Kremiller K, Kulkarni G, Gour A, Straub C J Med Chem. 2023; 67(1):529-542.

PMID: 38151460 PMC: 10872344. DOI: 10.1021/acs.jmedchem.3c01758.

Syntheses of Alkaloids: Reflections in the Chiral Pool.

Argade M, Riley A Synlett. 2023; 33(13):1209-1214.

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Synthesis of (-)-halichonic acid and (-)-halichonic acid B.

Reber K, Niner E Beilstein J Org Chem. 2022; 18:1629-1635.

PMID: 36530535 PMC: 9727271. DOI: 10.3762/bjoc.18.174.

What We Have Gained from Ibogaine: α3β4 Nicotinic Acetylcholine Receptor Inhibitors as Treatments for Substance Use Disorders.

Straub C, Rusali L, Kremiller K, Riley A J Med Chem. 2022; 66(1):107-121.

PMID: 36440853 PMC: 10034762. DOI: 10.1021/acs.jmedchem.2c01562.

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