Stereoselective Promiscuous Reactions Catalyzed by Lipases.

Angela Patti,Claudia Sanfilippo

doi:10.3390/ijms23052675

Angela Patti, Claudia Sanfilippo

Open Access

https://doi.org/10.3390/ijms23052675

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Abstract

The ability of lipases to display activity beyond their physiological reactions, so-called “catalytic promiscuity”, has gained increasing interest in the last two decades as an important tool for expanding the application of these enzymes in organic synthesis. Some lipases have been shown to be effective in catalyzing a variety of C-C bond formation reactions and most of the investigations have been directed to the optimization of the products yield through a careful tuning of the experimental parameters. Despite the fact that new stereogenic carbons are formed in many of the tested reactions, the target products have been often obtained in racemic form and examples of an efficient asymmetric induction by the used lipases are quite limited. The aim of this review, mainly focused on those lipase-catalyzed promiscuous reactions in which optically active products have been obtained, is to offer a current state of art together with a perspective in this field of asymmetric synthesis.

Highlights

Their condition promiscuity has been known since late 1980s when their ability to work in organic solvents was evidenced by Klibanov’s group [12] and more recently extended to other non-conventional media as ionic liquids (ILs) [13] or deep eutectic solvents (DES) [14]
Candida cylindracea dergo the nucleophilic addition of enolates, amines, thiols, and phosphines (Michael door Trichoderma viride were effective in catalyzing the addition water, nors) in the presence of a shown varietythe of most organocatalysts, metal-based or Lewisofacid catalysts thiols, and amines, leading the chiral products in moderate to good yield optical purity (41–71% ee) (Scheme 10)
Multicomponent reactions (MCRs) are attracting great interest as a powerful synthetic tool for the construction of multiple C-C bonds in a single step, without the need to isolate and purify intermediates, addressing the demand of more sustainable processes. For their low substrate specificity and “promiscuous activity”, lipases could be an ideal biocatalyst for MCRs, which often imply sequences of aldol condensation/Michael addition reactions

Summary

Introduction

Enzyme promiscuity has attracted great interest in the last decade as an emerging opportunity to further broaden the application of biocatalysis in organic synthesis and large investigations has been carried out on a variety of enzymes [7–10] as well as on the origin of promiscuity [11] In this context, lipases (triacylglycerol acylhydrolase, EC 3.1.1.3), which physiologically catalyze the hydrolysis of fats through the nucleophilic attack of water on an acyl-enzyme intermediate, occupy a place of honor for the displayed wide range of promiscuity. Lipases (triacylglycerol acylhydrolase, EC 3.1.1.3), which physiologically catalyze the hydrolysis of fats through the nucleophilic attack of water on an acyl-enzyme intermediate, occupy a place of honor for the displayed wide range of promiscuity Their condition promiscuity has been known since late 1980s when their ability to work in organic solvents was evidenced by Klibanov’s group [12] and more recently extended to other non-conventional media as ionic liquids (ILs) [13] or deep eutectic solvents (DES) [14].

Lipase-Catalyzed Aldol Reactions

Lipase-Catalyzed Michael Reactions

Lipase-Catalyzed Multicomponent Reactions

Findings

Conclusions