Synthesis of new acyclic nucleoside phosphonates (ANPs) substituted on the 1 ' and/or 2 ' positions

A series of 2' functionalized acyclic nucleoside phosphonate derivatives of 1-[3'-(phosphonomethoxy)propyl]uracil (1-4) have been synthesized together with the 1' and 2'-ethynyl derivatives of 9/1-[2'-(phosphonomethoxy)ethyl]adenine/thymine (5-7). Key intermediates leading to the latter series are (+/-)-[2-{diethyl(phosphonomethoxy)}-1-hydroxy]-but-3-yne (25) and (+/-)-diisopropyl{[2-hydroxy-4-(trimethylsilyl)but-3-yn-1-yl]oxy}methylphosphonate (30). Compounds 25 and 30 are easily obtained starting from (+/-)-solketal. (C) 2011 Elsevier Ltd. All rights reserved.