Solid‐Supported Diphosphitylating and Triphosphitylating Reagents for Nucleoside Modification

Abstract

This unit describes procedures for synthesis of diphosphitylating and triphosphitylating reagents. The synthesized reagents are first immobilized on appropriate polymer-bound linkers. Rigid and sterically hindered polymer-bound diphosphitylating and triphosphitylating reagents are then reacted selectively with the 5'-hydroxyl group of nucleosides in the presence of excess nucleosides. Typical oxidation with tert-butyl hydroperoxide, deprotection, and final cleavage of the products from the resins using a trifluoroacetic acid cocktail afford various nucleoside 5'-O-diphosphate and nucleoside 5'-O-triphosphate analogs. The use of the diphosphitylating and polymer-bound diphosphitylating reagents in preparation of oligodeoxynucleotides containing diphosphodiester internucleotide bridges is also described. This solid-phase strategy allows for the synthesis of the phosphorylated compounds without the need for nucleoside phosphate precursors, protected nucleosides, or purification of intermediates.