Solid‐Supported Reagents for Synthesis of Nucleoside Monothiophosphates, Dithiodiphosphates, and Trithiotriphosphates

Abstract

This unit describes procedures for the selective synthesis of nucleoside monothiophosphates, dithiodiphosphates, and trithiotriphosphates from solid-supported phosphitylating reagents. Rigid and sterically hindered polymer-bound 1,3,2-oxathiaphospholane is reacted selectively with the 5'-hydroxyl group of nucleosides in the presence of 1H-tetrazole. Sulfurization in the presence of Beaucage's reagent (3H-1,2-benzodithiole-3-one 1,1-dioxide) followed by ring-opening with 3-hydroxypropionitrile and basic cleavage in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) through the elimination of polymer-bound ethylene episulfide afford nucleoside monothiophosphates. Furthermore, reaction of polymer-bound diphosphitylating and triphosphitylating reagents, prepared from polymer-bound benzyl alcohol, with unprotected nucleosides, sulfurization with Beaucage's reagent, and acidic cleavage using trifluoroacetic acid cocktail produce nucleoside dithiodiphosphates and trithiotriphosphates in moderate yields.