Use of a Dihydroxyacetone Derivative as Protecting Reagent to Phosphorylate Oligonucleotides

We present here a new reagent enabling the supported synthesis of oligodeoxynucleotides (ODNs) and oligoribonucleotides (ORNs) containing a phosphate group at the 5′‐terminal position after complete deprotection. This reagent, derived from a dihydroxyacetone core, contains a dimethoxytrityl (DMTr) group. The procedure for final deprotection is very similar to that routinely used in the synthesis of unmodified ODNs or ORNs. In particular, it preserves the advantages of the “trityl‐on” method, namely facile purification by reverse‐phase high‐performance liquid chromatography (RP‐HPLC), short treatment with an acetic acid solution in water, the possibility of on‐resin monitoring by trityl cation assay, and the use of equipment commonly founded in chemical laboratories.