title: Scaleable processes for the synthesis of (-)-β-D-2,6-diaminopurine dioxolane (Amdoxovir, DAPD) and (-)-β-D-2-aminopurine dioxolane (APD).
abstract: 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.
authors.affiliation: Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, and Veterans Affairs Medical Center, Atlanta GA 30033, USA.
authors.forename: Longhu
authors.initials: L
authors.lastname: Zhou
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Coats
authors.forename: Hongwang
authors.initials: H
authors.lastname: Zhang
authors.forename: Shi
authors.initials: S
authors.lastname: Junxing
authors.forename: Drew R
authors.initials: DR
authors.lastname: Bobeck
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Schinazi