Promiscuous Acylases‐Catalyzed Markovnikov Addition of N‐Heterocycles to Vinyl Esters in Organic Media

Abstract

Three acylases, including d-aminoacylase from Escherichia coli, acylase "Amano" from Aspergillus oryzae and immobilized penicillin G acylase from Escherichia coli have been found to possess novel activity to catalyze the Markovnikov addition reaction of N-heterocycles to vinyl esters. The aza-Markovnikov addition reactions of 4-nitroimidazle to vinyl acetate catalyzed by d-aminoacylase, acylase "Amano" and immobilized penicillin G acylase were up to 1260-fold, 720-fold and 320-fold faster than the respective non-enzymatic reaction. Some control experiments have been designed to demonstrate the catalytic specificity of acylases. Under the catalysis of these promiscuous acylases, a number of N-heterocycles, including some pentacyclic N-heterocycles, pyrimidines and purines, were successfully added to a series of vinyl esters in moderate to excellent yields to prepare N-heterocycle derivatives. The acylase-catalyzed Markovnikov addition reaction has provided a new strategy to perform the Markovnikov addition and expanded the application of biocatalysts.

Characterization and mechanism insight of accelerated catalytic promiscuity of Sulfolobus tokodaii (ST0779) peptidase for aldol addition reaction

“…The hydrolase fold includes lipase, esterase, protease/peptidase, and dehalogenase etc. (López-Iglesias et al 2011;Sharma et al 2011;Wu et al 2006Wu et al , 2010Pazmiño et al 2007;Gotor-Fernández et al 2006;Dean et al 2007;Lou et al 2008;Li et al 2008;Branneby et al 2004;Nardini and Dijkstra 1999;Yuryev et al 2010;Daudé et al 2013;Wang et al 2014;Busto et al 2010;Kapoor and Gupta 2012), which Electronic supplementary material The online version of this article (doi:10.1007/s00253-015-6758-z) contains supplementary material, which is available to authorized users. has been widely identified as an important source of the enzymes that have promiscuous activities to catalyze a variety of C-C and C-N formation reactions (Hult and Berglund 2007;López-Iglesias et al 2011;Sharma et al 2011;Wu et al 2006;Pazmiño et al 2007;Gotor-Fernández et al 2006;Dean et al 2007;Lou et al 2008;Li et al 2008;Branneby et al 2004;Nardini and Dijkstra 1999;Yuryev et al 2010;Daudé et al 2013;Wang et al 2014).…”

“…In the efforts toward the identification and engineering of promiscuous enzymes, several successful cases have been reported, among which most of them belong to hydrolases to catalyze organic reactions (López-Iglesias et al 2011;Sharma et al 2011;Wu et al 2006;Pazmiño et al 2007;Gotor-Fernández et al 2006;Dean et al 2007;Lou et al 2008;Li et al 2008;Branneby et al 2004). The hydrolase fold includes lipase, esterase, protease/peptidase, and dehalogenase etc.…”

Promiscuous protease-catalyzed aldol reactions: A facile biocatalytic protocol for carbon–carbon bond formation in aqueous media

“…Although instances of several important addition reactions (e.g., Michael additions, Markovnikov additions, and direct Mannich reactions) have been frequently reported (Svedendahl et al, 2005;Torre et al, 2004;Wu et al, 2005;Wu et al, 2006;Li et al, 2009), the aldol reaction-widely considered to be one of the most basic and powerful tools for organic synthesis-has been seldom mentioned in published studies of promiscuous biocatalysts (Branneby et al, 2003;Li et al, 2008).…”

Promiscuous Zinc‐Dependent Acylase‐Mediated One‐Pot Synthesis of Monosaccharide‐Containing Pyrimidine Derivatives in Organic Medium

“…[18] In the enzymatic Michael additions of fluorouracil, bromouracil, uracil and thymine with vinyl acrylate, it is worthwhile to note that no Markovnikov adduct was detected by TLC and HPLC under the current conditions. The Michael addition activity of vinyl acrylate was much more favored than the Markovnikov addition.…”