Hybrid Solid/Solution-Phase Synthesis of Di- and Trinucleotides

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Recyclable solid-supported reagents were applied to a new solution-phase phosphoramidite approach. Nucleoside-3′-O-phosphoramidite 1 was coupled with a nucleoside 2 by using polyvinyl pyridinium tosylate as an activator to give the desired phosphite triester 3. The resulting triester 3 was treated with polystyrene-bound trimethylammonium tetrathionate or periodiate to give the phosphotriester or thiono-phosphotriester analogue 4. Treatment of 4 with p-toluenesulfonic acid gave the 5′-OH nucleoside 5. Representative results are shown in the scheme (81-96% yields, 88-96% purity).