Biocatalytic Aza‐Michael Addition of Aromatic Amines to Enone Using α‐Amylase in Water

Abstract

The Michael addition of amines with enones for synthesizing β‐amino carbonyls constitutes a valuable transformation in organic chemistry. While various catalyst have been made available for catalyzing the Michael addition of aromatic amines to enones but there is no report of using α‐amylase enzyme to catalyze this transformation. The α‐amylase from Aspergillus oryzae was found to catalyze the Michael addition of various aryl (hetero) amines to methyl vinyl ketone with high catalytic efficiency (63–83% yield). A hybrid of α‐amylase with copper nanoparticle (α‐amylase@CuNPs) has been prepared and used to catalyze this transformation as a reusable catalyst. Further, an application of α‐amylase catalyzed aza‐Michael addition in the cascade reactions has been exhibited by synthesizing biologically important 3‐acetyl quinoline. In addition, molecular docking and molecular dynamics (MD) simulation studies are carried out to get insight into the key interactions of the substrates with the amino acid residues near the active site and the probable reaction mechanism, which reveals Glu230 and Asn295 play a crucial role in the substrate activation process.

An Enzyme-Mediated Aza-Michael Addition Is Involved in the Biosynthesis of an Imidazoyl Hybrid Product of Conidiogenone B

“…This enzyme-mediated aza-Michael addition is analogous to that proposed for lipase B from Candida antarctica , which catalyzes the hydrolysis of triacylglycerols and also shows promiscuous activities such as aza-Michael addition of aniline compounds to acrylates . Another example is the α-amylase from A. oryzae , which catalyzes the hydrolysis of α-(1→4)-linkages in amylose; this enzyme was also reported to catalyze the aza-Michael addition of aromatic amines to enones . Our results show that the catalytic residues in the active site of Con-ABH can facilitate the aza-Michael addition of imidazole to 1 .…”

“…37 Another example is the α-amylase from A. oryzae, which catalyzes the hydrolysis of α-(1→4)-linkages in amylose; this enzyme was also reported to catalyze the aza-Michael addition of aromatic amines to enones. 38 Our results show that the catalytic residues in the active site of Con-ABH can facilitate the aza-Michael addition of imidazole to 1.…”

Promiscuous Lipase-Catalyzed Knoevenagel–Phospha–Michael Reaction for the Synthesis of Antimicrobial β-Phosphono Malonates

“…These results clearly show that the peculiar active site of CcL is responsible for the studied multicomponent reaction. In addition, two different non-enzymatic catalysts reported in the literature as sustainable promoters of Knoevenagel and Michael additions [ 50 , 51 , 52 , 53 ], copper (II) acetate and zinc oxide/palladium (II) acetate, were tested under similar reaction conditions leading to target product 1, with up to 23% yield ( Table 1 , entries 27–29). It is well recognized that the reaction medium has a great impact on enzyme properties [ 54 ].…”

Solvent Dependent Activity of Candida Antarctica lipase B and its Correlation with a Regioselective Mono Aza-Michael Addition- Experimental and Molecular Dynamics Simulation Studies

“…[10] So far, most related research within this area have focused on aza-Michael addition incorporating amines as the Michael donor. [11][12][13] However no research has been devoted to chemo-enzymatic aza-Michael addition involving amide as the Michael donor. Hydrazides are important amide intermediates [14] specifically due to their contribution to the synthesis of compounds showing biological properties, including antituberculous agent (Isoniazid), HIV inhibitors, inhibitors of myeloperoxidase, glycogen phosphorylase, and pesticides.…”