Aqueous chemistry is a key platform for advancing sustainable organometallic and enzymatic catalytic technologies relevant to API manufacturing. Effective implementation requires minimizing process mass intensity (PMI), increasing reaction mass efficiency, ensuring final product quality, and managing the impact of water-waste contaminants. Recent advances in palladium cross-coupling show how water or aqueous cosolvents can deliver highly efficient transformations: micellar water/sodium dodecyl sulfate/cyclopentylmethyl ether systems with new monodentate basic phosphines enable 0.125–0.5 mol% Pd and PMIs near 20 on complex architecture, while bidentate nitrogen ligands in hydroxyethyl pyrrolidone/water achieve 0.1–0.005 mol% Pd, turnover numbers up to 17,800, and >90% Pd recovery. Enzymatic innovations, including Merck’s free-enzyme cascade for islatravir and subtilisin-engineered peptide ligation for liraglutide, demonstrate how aqueous biocatalysis can provide selective, scalable, and greener API-relevant processes.
Tolomelli, A., Fantoni, T., Carboni, D., Ferrazzano, L., Cabri, W. (2026). Water-enabled organometallic and enzymatic catalysis: Sustainable technologies supporting API manufacturing. CURRENT OPINION IN GREEN AND SUSTAINABLE CHEMISTRY, 57, 1-7 [10.1016/j.cogsc.2025.101058].
Water-enabled organometallic and enzymatic catalysis: Sustainable technologies supporting API manufacturing
Alessandra Tolomelli;Tommaso Fantoni;Davide Carboni;Lucia Ferrazzano;Walter Cabri
2026
Abstract
Aqueous chemistry is a key platform for advancing sustainable organometallic and enzymatic catalytic technologies relevant to API manufacturing. Effective implementation requires minimizing process mass intensity (PMI), increasing reaction mass efficiency, ensuring final product quality, and managing the impact of water-waste contaminants. Recent advances in palladium cross-coupling show how water or aqueous cosolvents can deliver highly efficient transformations: micellar water/sodium dodecyl sulfate/cyclopentylmethyl ether systems with new monodentate basic phosphines enable 0.125–0.5 mol% Pd and PMIs near 20 on complex architecture, while bidentate nitrogen ligands in hydroxyethyl pyrrolidone/water achieve 0.1–0.005 mol% Pd, turnover numbers up to 17,800, and >90% Pd recovery. Enzymatic innovations, including Merck’s free-enzyme cascade for islatravir and subtilisin-engineered peptide ligation for liraglutide, demonstrate how aqueous biocatalysis can provide selective, scalable, and greener API-relevant processes.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
