Synthesis of Nucleoside Mono-, Di-, and Triphosphoramidates from Solid-Phase cyclo Saligenyl Phosphitylating Reagents
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.
Ahmadibeni, Yousef, Rakesh K. Tiwari, Gongqin Sun, and Keykavous Parang. "Synthesis of Nucleoside Mono-, Di-, and Triphosphoramidates from Solid-Phase cyclo Saligenyl Phosphitylating Reagents." Organic letters 11, no. 10 (2009): 2157-2160.
American Chemical Society