Continuous Flow Biocatalysis: Synthesis of Coumarin Carboxamide Derivatives by Lipase TL IM from Thermomyces lanuginosus

Coumarin carboxamide derivatives are important building blocks for organic synthesis and chemical biology due to their excellent biopharmaceutical properties. In this paper, we demonstrate for the first time a two-step enzymatic synthesis of coumarin carboxamide derivatives. Salicylaldehyde and dimethyl malonate were reacted to obtain coumarin carboxylate methyl derivatives, which were then reacted with various amines under the catalysis of lipase TL IM fromThermomyces lanuginosusto obtain coumarin carboxamide derivatives in continuous flow reactors. We studied various reaction parameters on the yields. The important features of this method include mild reaction conditions, a short reaction time (40 min), reduced environmental pollution, higher productivity (STY = 31.2941 g L−1h−1) and enzymes being relatively easy to obtain.Keywords:enzymatic synthesis;microreactor;coumarin carboxamide derivatives