Continuous-Flow Synthesis of β-Amino Acid Esters by Lipase-Catalyzed Michael Addition of Aromatic Amines

Abstract

A continuous-flow procedure for the synthesis of β-amino acid esters has been developed via lipase-catalyzed Michael reaction of various aromatic amines with acrylates. Lipase TL IM from Thermomyces lanuginosus was first used to catalyze Michael addition reaction of aromatic amines. Compared with other methods, the salient features of this work include green reaction conditions (methanol as reaction medium), short residence time (30 min), readily available catalyst and a reaction process that is easy to control. This enzymatic synthesis of β-amino acid esters performed in continuous-flow microreactors is an innovation that provides a new strategy for the fast biotransformation of β-amino acid esters.

Ring-Opening of Epoxides with Amines for Synthesis of β-Amino Alcohols in a Continuous-Flow Biocatalysis System

“…Biocatalysis shows good selectivity in organic synthesis, hence making it an environmentally friendly alternative to chemical synthesis [19][20][21][22]. Lipases have been extensively explored in Michael reactions, esterification and Knoevenagel-Michael cascade reactions to synthesize a variety of vital molecules related to foods, pharmaceuticals, flavorings and fine chemicals [23][24][25][26][27][28]. However, so far the synthesis of β-amino alcohols from the ring-opening of epoxides with aromatic amines catalyzed by enzymes has rarely been studied.…”

Biocatalytic Process Optimization

“…The optimized flow process (0.1 mL/min, 0.25 M of chloroacetaldehyde, and 0.5 M of acetaldehyde) produced 4.5 g of product per day in a bench-top reactor. Du et al [27] developed a continuous-flow procedure for the synthesis of β-amino acid esters via the lipase-catalyzed Michael reactions of various aromatic amines with acrylates. Seventeen β-amino acid esters were rapidly synthesized by lipase TL IM from Thermomyces lanuginosus in continuous-flow microreactors.…”