An expeditious route to methylphosphonate analogues of DNA

Protection of the exocyclic amino groups of both nucleobases adenine and guanine with the N,N-dimethylformamidine and cytosine with the isobutyryl group presents a convenient and economical N-protective-group-strategy for the solid-phase synthesis of DNA fragments containing methylphosphonate linkages at predetermined locations. Thus, the post-synthesis removal of the N-protective groups with hydrazine hydrate (16 h at 20°C) afforded immobilized fragments, which were then cleaved from the solid support and deprotected at the phosphorus by treatment with ammonia in methanol (2 h at 20°C) to yield high-quality products.

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