Solid-phase synthesis of dinucleoside and nucleoside-carbohydrate phosphodiesters and thiophosphodiesters

Unprotected nucleosides (ROH) were reacted with two polymers bound to N, N-diisopropylamino- 1,3,2-oxathiaphospholane in the presence of 1H-terazole. Oxidation with tertbutyl hydroperoxide or sulfurization with Beaucage's reagent, followed by the 1,3,2-oxathiaphospholane ring opening with unprotected nucleosides or carbohydrates (R'OH) in the presence of DBU, afforded nucleoside-(5'-5')-nucleoside or nucleoside- carbohydrate phosphodiester and thiophosphodiester derivatives through the elimination of polymer-bound ethylene episulfide. This strategy offers the advantages of facile isolation of final products and monosubstitution of unprotected nucleosides and carbohydrates.