Synthesis of Nucleoside Mono-, Di-, and Triphosphoramidates from Solid-Phase cyclo Saligenyl Phosphitylating Reagents

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Chloromethyl polystyrene resin was reacted with 5-hydroxysalicylaldehyde in the presence of potassium carbonate to afford polymer-bound 2-hydroxybenzaldehyde. Subsequent reduction with borane solution produced polymer-bound 2-hydroxybenzyl alcohol. The reaction of immobilized 2-hydroxybenzyl alcohol with appropriate phosphitylating reagents yielded solid-phase cyclosaligenyl mono-, di-, and triphosphitylating reagents, which were reacted with unprotected nucleosides, followed by iodine oxidation, deprotection of cyanoethoxy groups, and the basic cleavage, respectively, to afford 5'-O-nucleoside mono-, di-, and triphosphoramidates in 52-73% overall yield.


This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Organic Letters, volume 11, number 10, 2009 following peer review. The definitive publisher-authenticated version is available online at DOI: 10.1021/ol900320r.


American Chemical Society