Application of the “trimethyl lock”1 to Ganciclovir, a pro-prodrug with increased oral bioavailability

The synthesis and oral bioavailability of two potential prodrugs of Ganciclovir (1) based on the “trimethyl lock” is described. The mono-3-(2′-Acetoxy-4′6′-dimethylphenyl)-3,3-dimethylpropanoic ester (2) showed a four-fold increase in oral bioavailability over the parent drug in rats.