Scaleable processes for the synthesis of (-)-ß-D-2,6-diaminopurine dioxolane (Amdoxovir, DAPD) and (-)-ß-D-2-aminopurine dioxolane (APD).

An efficient and scalable synthesis of (-)-DAPD and (-)-APD has been developed. We discovered that t-butyl cyanoacetate can be used as a new additive for the sugar nucleoside base coupling step en route to DAPD with improved ß-selectivity and an isolated yield four fold greater than the original process scale method. Using this new process, (-)-DAPD has been prepared on greater than 20 g scale. In the synthesis of (-)-APD, a key enzyme-catalyzed hydrolysis reaction afforded the water-soluble deprotected α-anomer while leaving the ß-anomer completely untouched.