A novel method for the synthesis of DNA using 2'-deoxyribonucleoside 5'-phosphites as monomer units.

We propose a new method for the synthesis of DNA analogs completely different from the conventional methods (Scheme 1). Base-unprotected 2'-deoxyribo-nucleoside 5'-phosphites were employed as monomer units in this method. The 3'-OH of the monomer unit is condensed with the H-phosphonate monoester group at the 5'-terminus of the oligomer. The removal of the phosphite protecting groups gave the corresponding H-phosphonate monoester, which was allowed to condense with the 3'-OH of the monomer unit again. The synthesis of the monomer units by a simple one-step reaction from base-unprotected 2'-deoxyribo-nucleosides, and mild reaction conditions for the quantitative and rapid conversion of phosphites into H-phosphonate monoesters are described.