Diketo–Ketoenol Tautomers in Curcuminoids: Synthesis, Separation of Tautomers, and Kinetic and Structural Studies

Abstract

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.

Interactions between curcumin and human salt-induced kinase 3 elucidated from computational tools and experimental methods

“…Similar to other β-diketo compounds, the diketo (KK) and ketoenol (KE) tautomers of curcumin exist in equilibrium. Both these forms have different potencies to bind with biomolecules ( Rege et al, 2019 ; Osifova et al, 2022 ). Three polymorph crystal structures have been reported for curcumin (such as the monoclinic and orthorhombic forms) ( Supplementary Figure S10 ) ( Tonnesen et al, 1982 ; Parimita et al, 2007 ; Sanphui et al, 2011 ; Matlinska et al, 2018 ).…”

Structural study of some unsaturated malononitriles using mass spectrometry and theoretical models

“…Numerous cellular processes occur through tautomeric forms of compounds that potentially have tautomerizable groups, and a variety of reactions can be controlled through the displacement of this type of equilibrium. [1][2][3][4][5] Singh et al 6 described that tautomeric nucleoside analogs can act as antiviral drugs due to their ability to induce lethal mutagenesis. After many viruses, such as human immunodeficiency virus (HIV) and COVID-19, infect a cell, they rapidly begin making copies of their genetic material.…”