Oligodeoxynucleotide Synthesis: H-Phosphonate Approach

Ribonucleoside H-phosphonates were introduced by Todd in 1957 to prepare diribonucleotide phosphate diesters (1 ). The H-phosphonates were activated for condensation with diphenyl chlorophosphate, and this activator was later extended to the synthesis of deoxyribonucleotide dimers (2 ). Activation of deoxynucleoside H-phosphonates with acyl chlorides allows for the synthesis of oligodeoxynucleotides greater than 100 bases in length (3 ,4 ). Since these initial results, a number of laboratories have used acyl chlorides and nucleoside H-phosphonates in the synthesis of oligodeoxynucleotides (5 –9 ). This chemistry has also been extended to the synthesis of phosphate analogs of oligodeoxynucleotides (10 –16 ).