An expeditious route to methylphosphonate analogues of DNA

Abstract

AbstractProtection 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.