Lipase from Porcine Pancreas: An Efficient Biocatalyst for the Synthesis of ortho‐Aminocarbonitriles

Abstract

Enzymatic processes are highly specific, green, operate at mild conditions and reduce environmental pollution in comparison to conventional hazardous chemical processes. Herein, we describe a new strategy for the synthesis of ortho‐aminocarbonitriles by a multicomponent reaction of aromatic aldehydes, cyclohexanone and two equivalents of malononitrile at 40 °C. A new six‐membered ring was constructed by breaking seven bonds while four new bonds were formed. The solvent, lipase quantity and reaction conditions were optimized. The advantages of this biocatalyst mediated synthesis of ortho‐aminocarbonitriles comprised a one‐pot procedure with simple operations and higher yields, which were reported for the first time by biocatalysis.

Stereoselective Promiscuous Reactions Catalyzed by Lipases

“…Although several lipases are able to catalyze MCRs of malononitrile, aldehydes, and active carbonyl-containing compounds and this process has been applied to the one-pot synthesis of dihydropyran and chromene derivatives (Scheme 19), in most cases with excellent product yield and good functional group tolerance, no enantioselectivity was detected in all the cases [52][53][54][55][56]. Lipase from Candida Antarctica sp.…”

Bio-Catalysis in Multicomponent Reactions

“…The same group later on developed a new synthesis of ortho -aminocarbonitriles from aromatic aldehydes, cyclohexanone and malononitrile using porcine pancreas lipase (PPL) as the catalyst [ 89 ]. In another report, a one-pot synthesis of spiropyrazolo[3,4-b]pyridine and spiro-oxindole scaffolds catalyzed, respectively, by papain and catalase, was carried out starting from isatin, 1,3-dicarbonyls and 3-methyl-5-amino pyrazole [ 90 ] ( Scheme 6 ).…”

Lipase‐mediated multicomponent synthesis of 1H‐Pyrazolo[1,2‐b]phthalazine‐5,10‐dione derivatives in a binary solvent medium

“…50 In continuation of the interest in biocatalysis and biotechnology, recently, we reported the use of enzymes as a biocatalyst to the synthesis of important bioactive heterocyclic compounds. 51,52 The lipase-catalyzed Knoevenagel condensation of benzaldehyde, and malononitrile/ethyl cyanoacetate is reported in an ethanol-water solvent system. 53 Here; we report an environmentally safe protocol comprising aldehydes, malononitrile, and phthalhydrazide for the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives catalyzed by enzyme lipase from A. niger using water as a cosolvent.…”

“…Recently, this lipase is reported for the synthesis of butyl butyrate 50 . In continuation of the interest in biocatalysis and biotechnology, recently, we reported the use of enzymes as a biocatalyst to the synthesis of important bioactive heterocyclic compounds 51,52 . The lipase‐catalyzed Knoevenagel condensation of benzaldehyde, and malononitrile/ethyl cyanoacetate is reported in an ethanol–water solvent system 53 .…”