Diketo–ketoenol tautomers in curcuminoids: synthesis, separation of tautomers, and kinetic and structural studies

0559677 - ÚOCHB 2023 RIV US eng J - Journal Article
Osifová, Zuzana - Reiberger, Róbert - Císařová, I. - Machara, Aleš - Dračínský, Martin
Diketo–ketoenol tautomers in curcuminoids: synthesis, separation of tautomers, and kinetic and structural studies.
Journal of Organic Chemistry. Roč. 87, č. 15 (2022), s. 10309-10318. ISSN 0022-3263. E-ISSN 1520-6904
R&D Projects: GA ČR(CZ) GA22-15374S; GA ČR(CZ) GA22-16389S
Institutional support: RVO:61388963
Keywords : NF-κB * enol tautomerism * NMR spectroscopy
OECD category: Organic chemistry
Impact factor: 3.6, year: 2022
Method of publishing: Limited access
https://doi.org/10.1021/acs.joc.2c01357

Curcumin and its congeners exist in an equilibrium between diketo and ketoenol tautomers, which have different potencies to bind biomolecules. This work describes procedures for the preparation of 4-alkylated curcumin derivatives and the separation of their two tautomeric forms. Comprehensive NMR studies of the tautomer equilibria in various solvents have been accomplished. Additionally, a pure ketoenol tautomeric form of the active pharmaceutical ingredient (API) ASC-JM17 has been unequivocally determined by X-ray crystallography. Two different polymorphs of this API have been microscopically identified in the X-ray sample and manually separated, and a solid-state NMR study of the two polymorphs has also been performed. This work reports on the slow kinetics of diketo-ketoenol tautomerization in particular solvents that allow the separation and full characterization of both curcuminoids' tautomers.
Permanent Link: https://hdl.handle.net/11104/0332881


Research data: CCDC, CCDC