SOLID PHASE SYNTHESIS OF OLIGONUCLEOTIDE N3'}P5' PHOSPHORAMIDATES

摘要

The invention provides a method of synthesizing oligonucleotide N3'}P5' phosphoramidates using an amine-exchange reaction of phosphoramidites in which a deprotected 3'-amino group of a solid phase supported oligonucleotide chain is exchanged for the amino portion of a 5'-phosphoramidite of an incoming monomer which has a protected 3'-amino group. The resulting internucleotide phosphoramidite linkage is then oxidized to form a stable protected phosphoramidate linkage. The method of the invention greatly improves product yields and reduces reagent usage over currently available methods for synthesizing the above class of compound.