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HPLC‐ECD and TDDFT‐ECD study of hexahydropyrrolo[1,2‐a]quinoline derivatives
Author(s) -
Tóth László,
Mándi Attila,
Váradi Dániel,
Kovács Tibor,
Szabados Anna,
KissSzikszai Attila,
Gong Qi,
Zhang Haiyan,
Mátyus Péter,
Antus Sándor,
Kurtán Tibor
Publication year - 2018
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/chir.22969
Subject(s) - chemistry , time dependent density functional theory , absolute configuration , quinoline , moiety , circular dichroism , high performance liquid chromatography , enantiomer , density functional theory , chiral column chromatography , stereochemistry , chromatography , computational chemistry , organic chemistry
Synthesis of racemic hexahydropyrrolo[1,2‐a]quinoline derivatives ( 1 ‐ 8 ) was performed by utilizing the Knoevenagel‐[1,5]‐hydride shift‐cyclization domino reaction. Separation of the enantiomers of the chiral products ( 1 ‐ 8 ) was carried out by chiral high‐performance liquid chromatography, and online high‐performance liquid chromatography‐electronic circular dichroism (ECD) spectra were recorded to elucidate the absolute configuration by comparing the experimental and time‐dependent density functional theory‐ECD spectra obtained at various theoretical levels. For 1 of the products, the time‐dependent density functional theory‐ECD calculations allowed determining both the relative and the absolute configuration by distinguishing the 4 stereoisomers. One of the compounds with spiro 1,3‐cyclohexanedione moiety ( 7 ) possessed moderate acetylcholinesterase inhibitory activity, while 3 showed neuroprotective activity in oxygen‐glucose deprivation‐induced neurotoxicity in human neuroblastoma SH‐SY5Y cells.