Biocatalysis regioselective

It was reported that PEGylated lipase entrapped in PVA cryogel could be conveniently used in organic solvent biocatalysis [279], This method for enzyme immobilization is more convenient in comparison to other types of immobilization that take advantage of enzyme covalent linkage to insoluble matrix, since the chemical step which is time consuming and harmful to enzyme activity is avoided. The application of this catalytic system to the hydrolysis of acetoxycoumarins demonstrated the feasibility of proposed method in the hydrolysis products of pharmaceutical interest and to obtain regioselective enrichment of one of the two monodeacetylated derivatives. 

Biocatalysis has long been known as a green technology, capable of delivering highly stereo-, chemo- and regioselective transformations that can sometimes allow... 

Natural polyols have been used as substrates for the so-called combinatorial biocatalysis , a proposed approach to drug discovery [33]. For instance, complementary enzymatic regioselectivity was applied to produce a combinatorial library of 167 distinct selectively acylated derivatives of the flavonoid bergenin (11) on a robotic workstation [34]. Another lead compound, the antitumoral paclitaxel (12, a molecule with very low water solubility) has been similarly derivatized, initially exploiting the selectivity of the protease thermolysin for its side-chain C-2 OH. 

Regioselective reactions in systems which contain multiple functional groups are an area ideally suited for biocatalysis. Linhardt and co-workers at the University of Iowa s Division of Medicinal and Natural Products Chemistry recently published the synthesis of a series of 1 -O-acyl sucrose derivatives [31], Using Chiro-CLEC -BL (the CLC of subtilisin) and vinyl esters of the acylating agent in pyridine as solvent, the authors prepared l -O-lauryl sucrose, l -O-myristyl sucrose, and l -O-stearyl sucrose in 80-90% yield (Fig. 9). Their method represents a green alternative to the tin chemistry previously used [32],... 

Most fine chemical syntheses involve multiple steps including protection, catalysis, and deprotection operations. In those cases where exquisite enantio- or regioselectivity or specificity is demanded, then biocatalysis will be considered. The mild conditions often used for biocatalysis confer the added advantage of overcoming the need for protection and deprotection in many cases.4 Nevertheless, the enzymatic process will usually be one or at best a few steps, in an otherwise 10-20-step synthesis. Consequently, biocatalytic reactions are most normally preceded and followed by a chemical conversion. With this in mind, implementation needs to consider the integration of the biocatalytic step with the neighboring operations. 

The production of single enantiomers of drug intermediates is increasingly important in the pharmaceutical industry. Biocatalysis provides organic chemists an alternate opportunity to prepare pharmaceutically important chiral compounds. The advantages of biocatalysis over chemical catalysis are that enzyme-catalyzed reactions are stereoselective and regioselective, and can be carried out at ambient temperature and atmospheric pressure providing an environmentally friendly system. The selective examples presented in this... 

Biocatalysis, on the other hand, may be performed under mild conditions (low temperatures, neutral pH) thus affording high conversion yields and selective hydrolysis of the -CN functionality of compounds containing acid or base labile groups. Furthermore, enzyme hydrolysis is, in some instances, enantio- and/or regioselective. 

Biocatalysis usually exploits advantageous features of enzymes such as chemo-selectivity, regioselectivity, enantioselecivity and substrate spectrum of a certain broadness as depicted in Fig. 16.2-1. These points are addressed in examples in the following chapters. 

G. Li, A. Vaidya, W. Xie, W. Gao and R. A. Gross, Enzyme-Catalyzed Oligopeptide Synthesis Rapid Regioselective Oligomerization of L-Glutamic Acid Diethyl Ester Catalyzed by Papain , in ACS Symposium Series, ed. H. N. Cheng, American Chemical Society, 2008, vol. 999, Polymer Biocatalysis and Biomaterials II, p. 294. 

Enoate reductases (EC 1.3.1.31) are flavin-dependent and iron-sulfur-contain-ing proteins found among others in Clostridium species. Members of this NADHrflavin oxidoreductase/NADH oxidase family are distinguished from other ERs due to their high stereospecificity and strict regioselectivity for the reduction of double bonds of monoacids and monoesters, as well as reducing classical substrates such as a,p-unsaturated aldehydes, cyclic ketones, and methyl ketones. However, these enzymes are extremely oxygen sensitive, so they have not been employed in biocatalysis so far [2,3]. 

Bayer S, Birkemeyer C, Ballschmiter M. A nitrilase from a metagenomic library acts regioselectively on aliphatic dinitrUes [J]. Appl Microbiol Biotechnol 2011,89 (1) 91-98. Bomscheuer UT, Huisman GW, Kazlauskas RJ, Lutz S, Moore JC, Robins K. Engineering the third wave of biocatalysis [J]. Nature 2012, 485 (7397) 185-194. 

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