Current Organic Chemistry

ISSN: 1385-2728

Current Organic Chemistry
Volume 10, Number 11, July 2006

Contents

Recent Advances in Selective Biocatalysis
Guest Editor: Enzo Santaniello
Part II


Editorial Pp. 1195


Nucleoside Phosphorylases Pp. 1197-1215
E. S. Lewkowicz and A. M. Iribarren
[Abstract]


Biocatalytic Reduction of Carbonyl Groups Pp. 1217-1246
Kaoru Nakamura and Tomoko Matsuda
[Abstract]


Oxidations with Isolated and Cell-Bound Dehydrogenases and Oxidases Pp. 1247-1263
Francesco Molinari
[Abstract]


Enzyme Mediated Baeyer-Villiger Oxidations Pp. 1265-1287
Marko D. Mihovilovic
[Abstract]


Biocatalysis: Synthesis of Chiral Intermediates for Pharmaceuticals Pp. 1289-1321
Ramesh N. Patel
[Abstract]




Abstracts
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Editorial

This issue of Current Organic Chemistry constitutes the second part of a whole body of work dedicated to RECENT ADVANCES IN SELECTIVE BIOCATALYSIS. In Part II enzymatic activity related to nucleoside phosphorylases will be discussed (A. Iribarren). Biocatalytic reduction of carbonyl compounds (K. Nakamura), oxidations mediated by isolated or cell-bound dehydrogenases/oxidases (F. Molinari) as will as enzyme-catalyzed Baeyer-Villiger processes (M. D. Mihovilovic) will be also presented. Finally, the biocatalytic approach to the synthesis of chiral intermediates for pharmaceuticals will be reviewed (R. N. Patel).

A warm thank to renowned experts in the field that have accepted to contribute to Part I and Part II is deeply expressed. Their commitment is highly appreciated as an expression of competence and profound involvment in biocatalysis. All authors hope that the whole work will offer a useful contribution to biocatalysis, a well established field of investigation still open to new challenges and fascinating discoveries.

Enzo Santaniello
Università degli Studi di Milano
Milano, Italy


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Nucleoside Phosphorylases
E. S. Lewkowicz and A. M. Iribarren

Nucleoside phosphorylases (NPs) are transferases that catalyse the reversible cleavage of the glycosidic bond of ribo- or deoxyribo nucleosides, in the presence of inorganic phosphate, to generate the base and ribose- or deoxyribose-1-phosphate.

Since pyrimidine as well as purine nucleoside phosphorylases exist, the combination of both enzymes makes possible the generation of purine nucleosides from pyrimidine ones. As a consequence, NPs from different sources, mainly bacterial, have been exploited as tools for the enzymatic synthesis of nucleoside analogues. These molecules are extensively used as antiviral and anticancer agents because of their ability to act as reverse transcriptase inhibitors or chain terminators in RNA or DNA synthesis.

This review covers literature reports from 2000 on, focused mainly on the synthesis of nucleosides by free and immobilised microbial whole cells, along with some examples of modified nucleosides obtained by coupling transglycosylation to other enzymatic reactions.

The biological aspects of NPs are also discussed since they became an interesting target for clinical applications due to their key role in nucleotide metabolism. Finally, brief comments about their structures and catalytic mechanisms are included.


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Biocatalytic Reduction of Carbonyl Groups
Kaoru Nakamura and Tomoko Matsuda

Recent developments of biocatalytic reduction of carbonyl groups are reviewed. Methods to find, prepare and modify the biocatalysts and to improve productivity and enantioselectivity of the reactions are explained. Then, practical applications for the asymmetric reduction of carbonyl compounds with various functionalities are given, including the synthesis of pharmaceutically important compounds.


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Oxidations with Isolated and Cell-Bound Dehydrogenases and Oxidases
Francesco Molinari

Oxidations catalyzed by microbial dehydrogenases and oxidases allow for transformation of different molecules (primary and secondary alcohols, aldehydes, amines, saturated compounds) with high chemo-, regio- and enantioselectivity. Although only few bio-oxidations have been developed on large scale, the use of dehydrogenases and oxidases can be seen as a complementary tool to conventional synthetic methods. This review shows the advantages and the limitations of bio-oxidations catalyzed by whole microbial cells and/or isolated enzymes, with particular emphasis on the problem of cofactor recycling. The representative examples have been chosen trying to highlight how the problems of low selectivity or productivity can be overcome by using different techniques, such as the use of isolated enzymes and addition of coenzymes coupled with systems for regeneration of the coenzymes, genetic modification of the microorganism for knocking-out the degrading enzymes, recombination of the oxidative enzyme of interest in hosts with no overmetabolism, in situ extraction of the product, employment of microorganisms with “incomplete” oxidative metabolism, use of synthetic substrates leading to product not further modifiable.


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Enzyme Mediated Baeyer-Villiger Oxidations
Marko D. Mihovilovic

Oxygenation reactions of ketones to esters are referred to as Baeyer-Villiger oxidations and represent a powerful methodology in synthesis to break carbon-carbon bonds in an oxygen insertion process. Since the seminal work by Adolf Baeyer and Victor Villiger in 1899 substantial progress has been made to understand the mechanism, to predict migratory preference, and to apply this conversion in preparative chemistry. Stereoselective Baeyer-Villiger oxidation of cyclic ketones allows rapid access to chiral lactones as valuable intermediates in enantioselective synthesis. Together with organometal catalysts, biocatalysis offers a "green chemistry" methodology for this transformation. Several organisms have been identified to catalyze this reaction in the course of their metabolic pathways and an increasing number of flavin dependent monooxygenases is reported to accept a multitude of non-natural substrates. Such biocatalysts are used in synthetic chemistry either as isolated enzymes in combination with appropriate cofactor recycling systems or as living whole-cells in native or recombinant form. This review gives an overview of the most abundantly utilized enzymes and the corresponding substrate profiles together with applications in natural product and bioactive compound synthesis. The article focuses on recent developments in biocatalytic Baeyer-Villiger oxidation with promising applications in synthetic chemistry. Complementing these aspects, recent advances in characterizing the biochemistry of Baeyer-Villiger monooxygenases and novel approaches to modify and predict the catalytic performance of these enzymes, which have an impact on the potential as stereoselective catalytic entities, are discussed.


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Biocatalysis: Synthesis of Chiral Intermediates for Pharmaceuticals
Ramesh N. Patel

The production of single enantiomers of drug intermediates has become increasingly important in the pharmaceutical industry. Chiral intermediates and fine chemicals are in high demand by both the pharmaceutical and agrochemical industries for the preparation of bulk drug substances and agricultural products. The enormous potential of microorganisms and enzymes for the transformation of synthetic chemicals with high chemo-, regio- and enatioselectivities has been demonstrated. In this article, biocatalytic processes are described for the synthesis of chiral intermediates for anti-hypertensive drugs, lipid lowering drugs, anti-cancer agents, antiviral agents, β-3- and β-2-receptor receptor agonists, melatonin receptor agonists, a tryptase inhibitor, retinoic acid γ-specific antagonist, and anti-Alzheimer's drugs. Enzymatic acyloin condensation and carbobenzyloxy group deprotection reactions are also described.