Scaleable processes for the synthesis of (-)-β-d-2,6-diaminopurine dioxolane (Amdoxovir, DAPD) and (-)-β-d-2-aminopurine dioxolane (APD)

摘要

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 β-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 β-anomer completely untouched.