Biocatalysed synthesis of nucleosides and nucleotides

ELIZABETH LEWKOWICZ; LUIS IGLESIAS; JAVIER MONTSERRAT; ADOLFO IRIBARREN

Oviedo, España

Congreso; BIOTRANS 2007; 2007

Universidad de Oviedo

Nucleoside analogues have been extensively used in cancer and antiviral therapies as monomers and, more recently, for the synthesis of oligonucleotide therapeutics. As antiviral agents, nucleosides inhibit replication of the viral genome whereas anticancer compounds inhibit cellular DNA replication and repair. These molecules exert their action through different mechanisms such as inhibition of polymerases activity or acting as chain terminators in RNA or DNA synthesis. Different routes are being carried out in our laboratory to prepare nucleoside analogues by means of chemoenzymatic procedures. One of them starts from pentoses and makes use consecutively of isolated enzymes such as lipases, phosphopentomutase and purine nucleoside phosphorylases. In another route, purine nucleosides are prepared by microbial transglycosylation, starting from pyrimidine nucleosides. The required purine bases are commercially available or prepared by chemoenzymatic procedures. To improve the structural diversity, the hydroxylated derivatives of the nucleosides obtained as above described are generated by biocatalysed deamination. In addition, the preparation of nucleosides mono- and diphosphate using different strategies is also being developed.