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.