CHEMICAL SYNTHESIS OF OLIGODEOXYRIBONUCLEOTIDES USING N-UNPROTECTED H-PHOSPHONATE MONOMERS AND CARBONIUM AND PHOSPHONIUM CONDENSING REAGENTS - O-SELECTIVE PHOSPHONYLATION AND CONDENSATION

Oligodeoxyribonucleotides were synthesized using H-phosphonate monomer s without amino protection. The H-phosphonate monomers of deoxyadenosi ne, deoxycytidine, and deoxyguanosine bearing the free amino groups we re synthesized in good yields by O-selective phosphonylation of the pa rent 5'-O-(dimethoxytrityl)deoxyribonucleosides. It was found that the amino groups of the nucleosides were not modified during internucleot idic bond formation where (benzotriazol-1-yloxy)carbonium and -phospho nium compounds were employed as condensing reagents. The most effectiv e condensing reagent for rapid internucleotidic bond formation was fou nd to be riazol-1-yloxy)-1,1-dimethyl-2-hexafluorophosphate (BOMP). In the present H-phosphonate method, 2-(phenylsulfonyl)-3-(3-nitrophenyl )oxaziridine (PNO) was employed as a new oxidizing reagent for the oxi dation of internucleotidic H-phosphonate linkages under anhydrous cond itions in the presence of N,O-bis(trimethylsilyl)acetamide. The reacti on mechanism for the O-selective condensation was investigated in deta il by means of P-31 NMR spectroscopy. Unprecedented oxidation of the H -phosphonate monomers was observed during activation of the monomers w ith (benzotriazol-1-yloxy)phosphonium and -carbonium condensing reagen ts in the absence of the 5'-hydroxyl components. A mechanism for the O -selective condensation was proposed on the basis of ab initio molecul ar orbital calculations for the model compounds at the HF/6-31G level .