Synthesis of Guanine α-Carboxy Nucleoside Phosphonate (G-α-CNP), a direct inhibitor of multiple viral DNA polymerases.

The synthesis of guanine alpha-carboxy nucleoside phosphonate (G-alpha-CNP) is described. Two routes provide access to racemic G-alpha-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-alpha-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.