An Enzymatic Flow-Based Preparative Route to Vidarabine

• Lucia Tamborini¹*
• Clelia Previtali¹
• Francesca Annunziata¹
• Teodora Bavaro²
• Marco Terreni²
• Enrica Calleri²
• Francesca Rinaldi²
• Andrea Pinto³
• Giovanna Speranza⁴
• Daniela Ubiali²*
• Paola Conti¹

• ¹Department of Pharmaceutical Sciences, University of Milan, via Mangiagalli 25, 20133 Milano, Italy
• ²Department of Drug Sciences, University of Pavia, viale Taramelli 12, 27100 Pavia, Italy
• ³Department of Food, Environmental and Nutritional Sciences, University of Milan, via Celoria 2, 20133 Milano, Italy
• ⁴Department of Chemistry, University of Milan, via Golgi 19, 20133 Milano, Italy

The bi-enzymatic synthesis of the antiviral drug vidarabine (arabinosyladenine, ara-A), catalyzed by uridine phosphorylase from Clostridium perfringens (CpUP) and a purine nucleoside phosphorylase from Aeromonas hydrophila (AhPNP), was re-designed under continuous-flow conditions. Glyoxyl–agarose and EziGTM1 (Opal) were used as immobilization carriers for carrying out this preparative biotransformation. Upon setting-up reaction parameters (substrate concentration and molar ratio, temperature, pressure, residence time), 1 g of vidarabine was obtained in 55% isolated yield and >99% purity by simply running the flow reactor for 1 week and then collecting (by filtration) the nucleoside precipitated out of the exiting flow. Taking into account the substrate specificity of CpUP and AhPNP, the results obtained pave the way to the use of the CpUP/AhPNP-based bioreactor for the preparation of other purine nucleosides.

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