Hydroxycinnamic acids, known for their health benefits and widespread presence in plant-based food, undergo complex transformations during high-temperature processing. Recent studies revealed a high browning potential of hydroxycinnamic acids and reactive Maillard reaction intermediates, but the role of phenolic compounds in the early stage of these reactions is not unambiguously understood. Therefore, we investigated the influence of caffeic acid and ferulic acid on the nonenzymatic browning of arabinose, galactose, and/or alanine, focusing on the implications on the formation of relevant early-stage Maillard intermediates and phenol-deriving products. Contrary to previous assumptions, hydroxycinnamic acids were found to promote nonenzymatic browning instead of solely trapping reactive intermediates. This was reflected by an intense browning, which was attributed to the formation of heterogeneous phenol-containing Maillard products. Although, caffeic acid is more reactive than ferulic acid, the formation of reactive furan derivatives and of heterogeneous phenol-containing colorants was promoted in the presence of both hydroxycinnamic acids.

Non-enzymatic conversion of phenolic compounds plays an important role during thermal processing of plant-based food such as coffee, cocoa, and peanuts. However, the more prominent Maillard reaction is mainly studied at a mechanistic level for carbohydrates and amino compounds to clarify reactions that contribute to (\'classic\') melanoidin formation, but the role of phenolic compounds in such reactions is rarely discussed yet. To understand their contribution to non-enzymatic browning, reactions between ubiquitous phenolic acids, such as caffeic acid and ferulic acid, and prominent heterocyclic Maillard intermediates, namely furfural, hydroxymethylfurfural, and pyrrole-2-carbaldehyde were investigated. Following incubation under roasting conditions (220 °C, 0-30 min), heterogenous products were characterized by high-resolution mass spectrometry, and, after isolation, by nuclear magnetic resonance spectroscopy. By this, color precursors were identified, and it was shown that in addition to aromatic electrophilic substitution, nucleophilic and condensation reactions are key mechanisms contributing to the formation of phenol-containing melanoidins.

Pyrrole-ligated 1,3,4-oxadiazole is a very important pharmacophore which exhibits broad therapeutic effects such as anti-tuberculosis, anti-epileptic, anti-HIV, anti-cancer, anti-inflammatory, antioxidant, and antibacterial activities. A one-pot Maillard reaction between D-Ribose and an L-amino methyl ester in DMSO with oxalic acid at 2.5 atm and 80 °C expeditiously produced pyrrole-2-carbaldehyde platform chemicals in reasonable yields, which were utilized for the synthesis of pyrrole-ligated 1,3,4-oxadiazoles. Benzohydrazide reacted with the formyl group of the pyrrole platforms to provide the corresponding imine intermediates, which underwent I2-mediated oxidative cyclization to the pyrrole-ligated 1,3,4-oxadiazole skeleton. The structure and activity relationship (SAR) of the target compounds with varying alkyl or aryl substituents of the amino acids and electron-withdrawing or electron-donating substituents on the phenyl ring of benzohydrazide were evaluated for antibacterial activity against Escherichia coli, Staphylococcus aureus, and Acinetobacter baumannii as representative Gram(-) and Gram(+) bacteria. Branched alkyl groups from the amino acid showed better antibacterial activities. Absolutely superior activities were observed for 5f-1 with an iodophenol substituent against A. baumannii (MIC < 2 μg/mL), a bacterial pathogen that displays a high resistance to commonly used antibiotics.

Nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) are indispensable analytical tools to provide chemical fingerprints in metabolomics studies. The present study evaluated radiation breeding wheat lines for chemical changes by non-targeted NMR-based metabolomics analysis of bran extracts. Multivariate analysis following spectral binning suggested pyrrole-2-carbaldehydes as chemical markers of four mutant lines with distinct NMR fingerprints in a δH range of 9.28-9.40 ppm. Further NMR and MS data analysis, along with chromatographic fractionation and synthetic preparation, aimed at structure identification of marker metabolites and identified five pyrrole-2-carbaldehydes. Quantum-mechanical driven 1H iterative full spin analysis (QM-HiFSA) on synthetic pyrrole-2-carbaldehydes provided a precise description of complex peak patterns. Biological evaluation of pyrrole-2-carbaldehydes was performed with nine synthetic products, and six compounds showed hepatoprotective effects via modulation of reactive oxygen species production. Given that three out of five identified in wheat bran of radiation were described for hepatoprotective activity, the value of radiation mutation to greatly enhance pyrrole-2-carbaldehyde production was supported.