Synthesis and selective cleavage of oligodeoxyribonucleotides containing non-chiral internucleotide phosphoramidate...

Oligodeoxynucleotides containing phosphoramidate internucleotide links 3'-OP(O)NH-5' have been prepared using standard solid phase phosphoramidite techniques. For the incorporation of the phosphoramidate linkages we have used monomer as well as dimer building blocks. With the monomer 3'-phosphoramidite building blocks, which are derived from 5'-amino-2',5'-dideoxynucleosides, it is possible to incorporate phosphoramidate links into specific positions within an oligodeoxynucleotide. Furthermore the synthesis of several dinucleoside phosphate derivatives which are linked by phosphoramidate bonds are described. The internucleotide phosphoramidate linkage was performed using the Staudinger reaction followed by a Michaelis-Arbuzov type transformation. After 3'-phosphitylation these dinucleosides are compatible with the current phosphoramidite methodology of oligodeoxynucleotide synthesis.