Synthesis of Guanine α-Carboxy Nucleoside Phosphonate (G-α-CNP), a Direct Inhibitor of Multiple Viral DNA Polymerases
- Nuala M. MaguireNuala M. MaguireSchool of Chemistry, Analytical and Biological Chemistry Research Facility, University College Cork, Cork, IrelandMore by Nuala M. Maguire
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- Alan FordAlan FordSchool of Chemistry, Analytical and Biological Chemistry Research Facility, University College Cork, Cork, IrelandMore by Alan Ford
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- Jan BalzariniJan BalzariniRega Institute for Medical Research, KU Leuven, B-3000 Leuven, BelgiumMore by Jan Balzarini
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- Anita R. Maguire*Anita R. Maguire*E-mail: [email protected]School of Chemistry and School of Pharmacy, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork, Cork, IrelandMore by Anita R. Maguire
Abstract
The synthesis of guanine α-carboxy nucleoside phosphonate (G-α-CNP) is described. Two routes provide access to racemic G-α-CNP 9, one via base construction and the other utilizing Tsuji–Trost allylic substitution. The latter methodology was also applied to the enantiopure synthesis of both antipodes of G-α-CNP, each of which showing interesting antiviral DNA polymerase activity. Additionally, we report an improved multigram scale preparation of the cyclopentene building block 10, starting material for the preferred Tsuji–Trost route to 9.
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