Chemoenzymatic Transformations in Nucleoside Chemistry
The synthetic potential of enzymes in connection with nucleoside analogue preparations is described.
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Summary. The synthetic potential of enzymes in connection with nucleoside analogue preparations is described. Keywords. Enzymes; Nucleosides; Chemoenzymatic transformations.
Introduction During the last quarter of the century almost no other aspect of organic synthesis has received as much attention as the preparation of enantiomerically pure compounds. The synthesis of optically active materials is an important task and represents a challenge to synthetic organic chemists. Increasing interest in the understanding of biological processes and the general recognition that chirality plays a crucial role in nature fostered a tremendous effort in enantioselective synthesis . Nowadays, the choice of a racemic synthesis over the development of an enantiopure compound must be justified, since opposite enantiomers interact differently within an organism and can display various activities . Thus, each country requires investigation into the bio-availability and pharmacological effect of a new chiral drug, and its final approval is based on complete background information for each enantiomer. The chemistry of natural nucleosides and their analogues has been thoroughly studied due to their potential as fungicidal, antitumour, and antiviral agents [1]. Consequently, extensive modifications have been made to both the heterocyclic base and the sugar moiety in order to avoid the drawbacks shown by nucleosides or analogues in certain applications. Since the late eighties, nucleoside analogue s have been investigated with renewed urgency in the search for agents effective against the Human Immunodeficiency Virus (HIV), the causative agent of AIDS. More effective treatment has also been sought for other viral infections, in particular those caused by Herpes Simplex Virus (HSV types 1 and 2), Varicella Zoster Virus (VZV), Human Cytomegalovirus (HCMV), and Epstein-Barr Virus
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Corresponding author
H. Griengl (ed.), Biocatalysis © Springer-Verlag Wien 2000
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M. Ferrero and V. Gotor
(EBV), which can prove lethal to AIDS patients and other immunocompromised individuals. This has resulted in an explosion of synthetic activity in the field of nucleosides, with special interest in their asymmetric syntheses, and in the discovery of a number of derivatives with potential antiviral activity. For organic chemists, enzyme-catalyzed reactions have become standard procedures for the synthesis of enantiomerically pure compounds due to their simple feasibility and high efficiency. In general, these catalysts are inexpensive and in many cases able to fit to a wide range of substrate structures. Moreover, biocatalysts are ecologically beneficial natural catalysts. Due to these advantages, it is to be expected that biocatalyzed reactions will play an increasing role primarily in the preparation of nonracemic chiral biologically active compounds in the laboratory as well as in industrial production. A number of extensive general reviews [2], special issues of periodicals [3], or specialized books [4] have been published during the last two deca
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