Synthesis and Stability of Nucleoside 3′,5′-Cyclic Phosphate Triesters Masked with Enzymatically and Thermally Labile Phosphate Protecting Groups

Appropriately protected structurally modified nucleoside 3′,5′-cyclic monophosphates are known to show antiviral activity. For this reason, a straightforward synthesis of nucleoside 3′,5′-cyclic phosphates protected with three different enzymatically removable groups, viz. 3-acetyloxy-2,2-bis(ethoxycarbonyl)propyl (in 1 and 4), 4-acetylthio-2,2-dimethyl-3-oxobutyl (in 2), and 4-(tert-butyldisulfanyl)-2,2-dimethyl-3-oxobutyl (in 3) groups, is described. Removal of these protecting groups at pH 7.5 and 37 °C was monitored by reverse-phase HPLC.