Microwave-Accelerated\nSynthesis of Novel Triphosphate\nNucleoside Prodrugs: Expanding the Therapeutic Arsenal of Anticancer\nAgents

In this study, we report for the first time a microwave-accelerated\nsynthesis of purine and pyrimidine nucleoside triphosphate prodrugs,\nwhose γ phosphate is masked with an aryloxy moiety and an amino\nacid ester (γ-ProTriP). The synthetic utility of this method\nis illustrated by the synthesis of triphosphate prodrugs of clofarabine\nand gemcitabine, two FDA-approved anticancer drugs. These new prodrugs\nshowed good chemical and rat serum stability. Remarkably the clofarabine\nprodrug showed significant cytotoxicity against a panel of cancer\ncell lines.