Mechanistic Insights Into Catechin Epimerization: Interplay of Deprotonation and Quinone Methide Stabilization

Catechin epimerization occurs during thermal processing of tea and can influence its bioactivity and nutritional properties. However, the structural factors governing epimerization behavior remain incompletely understood. In this study, we systematically investigated the effects of chemical structure on epimerization using native catechins and a series of model compounds under heating conditions relevant to food processing. The time‐dependent changes in peak area ratios during epimerization and the equilibrium ratios were evaluated by HPLC analysis, and the observed trends were interpreted using density functional theory (DFT) calculations. The results demonstrate that epimerization is influenced by both the acidity (p K a ) of the 4′‐hydroxyl group and stability of the quinone methide intermediate, and is governed by the interplay between these factors. Electronic effects on the B‐ring were found to influence deprotonation of the 4′‐hydroxyl group, whereas intramolecular hydrogen‐bonding interactions contributed to stabilization of the quinone methide intermediate. Substituents at the C3 position further influence both epimerization profile and equilibrium ratio through electronic and steric effects. These findings establish a mechanistic framework for catechin epimerization and provide insight into structure–reactivity relationships in polyphenolic systems undergoing quinone methide‐mediated transformations.