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Current Organic Chemistry, Volume 7, No. 13, 2003

 

Contents

 

Enzymatic Catalysis

Guest Editor: Bruno Danieli

 

Synthetic Applications of Nitrile-Converting Enzymes Pp. 1279-1295

Veronika Mylerova and Ludmila Martinkovwa

[Abstract]

 

Properties and Synthetic Applications of Ammonia-Lyases Pp. 1297-1315

Laszlo Poppe and Janos Retey

[Abstract]

 

Laccases and Phenol Oxidases in Organic Synthesis – a Review Pp. 1317-1331

Stephanie G. Burton

[Abstract]

 

Biocatalysis in Reaction Mixtures with Undissolved Solid Substrates and Products Pp. 1333-1346

Rein V. Ulijn, Luigi De Martin, Lucia Gardossi and Peter J. Halling

[Abstract]

 

Enzyme-Mediated Syntheses of Chiral Communication Substances: Fragrances for Perfumery Applications Pp. 1347-1367

Elisabetta Brenna

[Abstract]

 

Microbial/Enzymatic Synthesis of Chiral Intermediates for Pharmaceuticals:Case Studies from BMS Pp. 1369-1386

Ramesh N. Patel

[Abstract]

 

Enzymatic Synthesis of Polyphenols Pp. 1387-1397

Hiroshi Uyama and Shiro Kobayashi

[Abstract]

 

Enzyme Applications in Detergency and in Manufacturing Industries Pp. 1399-1422

Yves M. Galante and Cristina Formantici

[Abstract]

 

Abstracts

 

[Back to top] Synthetic Applications of Nitrile-Converting Enzymes

Ludmila Martinkova and Veronika Mylerova

 

The use of nitrile hydratases (RCN + H2O RCONH2) and nitrilases (RCN + 2 H2O RCOO- + NH4+) in biocatalysis attracts profound attention from the beginning of 1980s since it provides a useful alternative to the conventional nitrile hydrolysis using strong acid or base catalysts. In the past 5 years the potential of this branch of biotransformations has been broadened significantly by both the isolation of new mesophilic and thermophilic nitrile-metabolizing microorganisms and the purification of new nitrile-converting enzymes, including thermostable ones. Currently, the scope of products afforded by nitrile-converting biocatalysts encompass hundreds of compounds such as aliphatic, alicyclic, aromatic and heterocyclic carboxylic acids and their amides. New nitrile hydratases show high enantioselectivity towards racemic substituted 2-arylpropionitriles, 2-arylbutyronitriles and prochiral 3-arylglutaronitriles. Synthesis of optically active -hydroxy and -fluoro amides and acids employs whole-cell biocatalysts or purified nitrilases. (E)-Selectivity for ,ß-unsaturated nitriles and cis- or trans-selectivity for alicyclic nitriles is also demonstrated with some nitrile-converting enzymes. Regioselectivity and chemoselectivity of the biocatalysts enable preparation of diverse functional group-containing products such as cyanocarboxylic acids, cyanoamides, hemiesters and their amides and carboxylic acids and amides with ether groups. Stabilization of the nitrile-converting biocatalysts is achieved by entrapment in hydrogels or by lyophilization. Organic-aqueous mixtures are suitable as reaction media for numerous nitrile-converting enzymes.

 

[Back to top] Properties and Synthetic Applications of Ammonia-Lyases

Laszlo Poppe and Janos Retey

 

Ammonia-lyases catalyze a wide range of processes leading to ,-unsaturated compounds by elimination of ammonia having few features in common. They utilize an extraordinary range of prosthetic groups; e.g. coenzyme B12, dipyrromethane cofactor, pyridoxal-phosphate, or the 3,5-dihydro-5-methylidene-4H-imidazol-4-one (MIO) prosthetic groups. In this work, ammonia-lyases are reviewed with major emphasis on various aspects of biotransformations, covering topics from the fundamental biochemistry of ammonia-lyases to their structure determined by protein crystallography.

 

[Back to top] Laccases and Phenol Oxidases in Organic Synthesis – a Review

Stephanie G. Burton

 

This is a review of recent progress in developing biocatalytic reactions involving two major groups of phenol oxidases, viz., laccases (benzenediol:oxygen oxidoreductase E.C. 1.10.13.2) and polyphenol oxidases (phenol: oxygen oxidoreductase, E.C. 1.14.18.1, also known as tyrosinase). Oxidases catalyse reactions involving direct activation of oxygen, and within this group, the multi-copper oxidases catalyse the four-electron reduction of oxygen to water with the concomitant one-electron oxidation of a substrate. Such reactions, applied in biocatalytic systems, provide effective methods to achieve oxyfunctionalisation, (particularly asymmetric oxyfunctionalisation reactions) and routes to controlled and predictable formation of oxy- and hydroxylated products, and polymers. The review includes discussion of the characteristics of these enzymes which are of relevance to their application as biocatalysts.

 

[Back to top] Biocatalysis in Reaction Mixtures with Undissolved Solid Substrates and Products

Rein V. Ulijn, Luigi De Martin, Lucia Gardossi and Peter J. Halling

 

Enzymatic synthesis in reaction mixtures with mainly undissolved substrates and/or products is a synthetic strategy in which the compounds are present mostly as pure solids. It retains the main advantages of conventional enzymatic synthesis such as high regio- and stereoselectivity, absence of racemisation and reduced side-chain protection. The reaction yields are improved and the necessity to use organic solvents to shift the thermodynamic equilibrium toward synthesis is reduced by product precipitation, which makes the synthesis favourable even in water.

 

The thermodynamics of these reaction systems have been investigated in the last few years, resulting in methods to predict the direction of a typical reaction a priori. Furthermore, studies on kinetics, enzyme concentration, pH/temperature effects, mixing and solvent selection have opened new perspectives for the understanding, modelling, optimisation and the possible large scale application of such a strategy. In this review we have tried to cover most of the literature published in the last five to ten years on biocatalysis in substrate suspensions, focusing especially on cases where the reaction products precipitate.

 

[Back to top] Enzyme-Mediated Syntheses of Chiral Communication Substances: Fragrances for Perfumery Applications

Elisabetta Brenna

 

This work describes the use of enzyme-mediated reactions for the preparation of enantiomerically enriched chiral fragrances. The main floral, musk and woody-ambery odorants employed in fine and functional perfumery are taken into consideration.

 

[Back to top] Microbial/Enzymatic Synthesis of Chiral Intermediates for Pharmaceuticals:Case Studies from BMS

Ramesh N. Patel

 

There has been an increasing awareness of the enormous potential of microorganisms and enzymes for the transformation of synthetic chemicals with high chemo-, regio- and enatioselective manner. Chiral intermediates are in high demand from pharmaceutical industries for the preparation bulk drug substances. In this review article, microbial/enzymatic processes mainly taken from the research carried out at BMS have been described for the synthesis of chiral intermediates for antihypertensive drugs, anticholesterol drugs, anticancer agents, antiviral agents, b3-receptor receptor agonists, melatonin receptor agonists, and anti-Alzheimer's drugs.

 

[Back to top] Enzymatic Synthesis of Polyphenols

Hiroshi Uyama and Shiro Kobayashi

 

In vitro synthesis of polyphenols using isolated enzymes as catalyst via non-biosynthetic pathways is reviewed. Various phenols have been subjected to an oxidative polymerization catalyzed by peroxidase, laccase, or bilirubin oxidase under mild reaction conditions. In most cases, polyphenols with a mixed structure of phenylene and oxyphenylene units have been formed. By utilizing specific enzymatic catalysis, regio- and chemoselective polymerizations have occurred, yielding functional and useful polymers, which are often difficult to synthesize by conventional methodologies. Enzymatic curing of urushiol analogues produces crosslinked polymeric films ("artificial urushi") with high hardness and good elasticity.

 

[Back to top] Enzyme Applications in Detergency and in Manufacturing Industries

Yves M. Galante and Cristina Formantici

 

Applications of enzymes in industrial and food processes have undergone remarkable developments in several areas in the last 10-20 years: detergent, textile, grain wet milling, food, monogastric animal feed, pulp & paper, leather, natural polymer modifications, organic chemical synthesis, diagnostics, etc.

 

Recombinant DNA technology and protein engineering are currently the main technologies in the design and production of new industrial enzymes, because they allow to reach high production yields of purified products at competitive costs and to design new enzymes with novel properties well adapted to industrial conditions.

 

Of the major classes of enzymes, about 80% of current industrial enzymes are hydrolases (e.g., carbohydrolases, esterases) and are extracellularly produced for ease of downstream recovery after fermentation. In recent years, a few oxidoreductases have been commercially introduced (e.g., catalase, peroxidase, laccase) and even one lyase (pectate lyase for raw cotton bioscouring).

 

In this review, we give an overview of enzyme applications in: detergency, textile and leather, which are the three areas that represent the majority of industrial enzyme uses.

 

In detergency, enzymes contribute to the highly efficient removal of stains made of proteins, starch and grease from garments and fabrics, thereby enhancing the action of surfactants and improving the performance of the washing process.

 

In the textile industry, cellulases, amylases, proteases, catalases, pectin lyase, peroxidase and laccase, have all become enzymes commonly used in textile mills, dyehouses and industrial laundries.

 

In tanneries, application of proteases at the bating step to soften the hides and prepare them for tanning has been a key step in leather making ever since ancient times. A vast range of proteases is now available for soaking, bating and for unhairing raw hides, and of lipases for degreasing.