Amide Synthesis via Aminolysis of Ester or Acid with an Intracellular Lipase

Abstract

A unique lipase (SpL) from Sphingomonas sp. HXN-200 was discovered as the first intracellular enzyme for the aminolysis of ester or acid to produce amide. Reactions of a series of esters and amines with SpL gave the corresponding amides 3a–g in high yield with high activity. SpL also showed high enantioselectivity and high activity for enantioselective ester aminolysis, producing amides (R)-3h–j in high ee from the corresponding racemic ester or amine. Moreover, SpL was found to be highly active for the aminolysis of carboxylic acid, which was generally considered infeasible with the known aminolysis enzymes. The aminolysis of several carboxylic acids afforded the corresponding amides 3a, 3d, 3k, 3l, and 3n in good yield. The intracellular SpL was expressed in Escherichia coli cells to give an efficient whole-cell biocatalyst for amide synthesis. Remarkably, high catalytic activity was observed in the presence of water at 2–4% (v/v) for free enzyme and 16% (v/v) for whole cells, respectively. Accordingly, E. coli (SpL) wet cells were used as easily available and practical catalysts for the aminolysis of ester or acid, producing a group of useful and valuable amides in high concentration (up to 103 mM) and high yield. The newly discovered intracellular SpL with unique properties is a promising catalyst for green and efficient synthesis of amides.

Biocatalysis: Enzymatic Synthesis for Industrial Applications

“…Recently,aunique lipase was discovered for aminolysis of several esters (even acids) with several amines to produce amides in high yields in the presence of water (partially hydrated hexane). [144] Amide synthesis with ATP-activation can directly use acids and amines in an aqueous environment. At eam from GSK combined CoA ligases (CLs) and N-acyltransferases (NATs) to produce amides (Scheme 33).…”

Novozym 435: the “perfect” lipase immobilized biocatalyst?

“…42 The heterogeneity of the natural substrate [43][44][45][46][47][48] has converted lipases in enzymes with a very broad specificity, accepting substrates very different from glycerides (even amides). Thus, lipases are used in vitro to catalyze reactions different from those of the natural hydrolase function, [49][50][51][52][53][54] such as esterification, [55][56][57][58][59][60][61] acidolysis, [62][63][64][65][66][67] interesterificaton, [68][69][70][71] transesterification, [72][73][74][75][76] aminolysis, [77][78][79][80][81] perhydrolysis, 82,83 etc., together with a collection of the so-called promiscuous reactions. [84][85][86][87][88]...…”

Biocatalysis: A Pharma Perspective

“…A collaboration with Professor Li's group at the National University of Singapore led to the discovery and early application of SpL, a lipase from Sphingomonas sp. HXN‐200 . This remarkable intracellular lipase was demonstrated to undergo amide bond forming reactions on a variety of both methyl esters and, remarkably, carboxylic acids.…”