Solvent-free synthesis of chalcones for enzymatic biotransformation reactions

The use of biotransformation through enzymatic fungal secretomes has proved to be an effective strategy for generating new molecules from readily available natural products [ 1 ] [ 2 ] [ 3 ] [ 4 ]. After applying this methodology to stilbenes [ 1 ] [ 2 ] [ 3 ] [ 4 ], we were able to generate a series of compounds with particularly interesting structures from chalcones. Based on the reaction mechanisms observed during the synthesis of these compounds, additional chalcones were synthesized with phenol substitutions to enhance reaction selectivity. A green chemistry approach, a solvent-free Claisen-Schmidt condensation reaction [ 5 ] was used to achieve this. It is cost-effective, energy-efficient, and often results in higher yields, improved selectivity, and shorter reaction times. The reactions allow real-time monitoring using nuclear magnetic resonance (NMR), which facilitated precise optimization of the conditions. The newly synthesized chalcones were purified by flash or semipreparative chromatography and subsequently biotransformed using laccases from Trametes versicolor . The biotransformation mixtures were purified by high-resolution preparative chromatography in combination with a dry-load technique. Full de novo structure elucidation was achieved for all biotransformed compounds. The resulting structures confirmed the hypothesized reaction pathways, which were based on phenoxy radical coupling mechanisms. The antimicrobial activity of the newly generated compounds was then evaluated against Gram-positive and Gram-negative bacteria. This approach exemplifies the integration of green synthetic methods and enzymatic biotransformation to expand chemical diversity and explore bioactive properties in drug discovery pipelines. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany