Photocleavable protecting groups as nucleobase protections allowed the solid-phase synthesis of base-sensitive SATE-prooligonucleotides

The first synthesis of oligodeoxynucleotide heteropolymers carrying base-sensitive S-pivaloylthioethyl (t-Bu-SATE) phosphotriester linkages has been performed. It is based on the use of 6-nitroveratryloxycarbonyl (NVOC) and 2,2'-bis(2-nitrophenyl)ethoxycarbonyl (diNPEOC) groups as nucleobase protections in combination with photolysis deprotection. The synthesis was realized using the phosphoramidite approach on solid support bearing a 1-(o-nitrophenyl)-1,3-propanediol linker. The removal of the protecting groups and the cleavage of the oligonucleotides from the solid support were accomplished in a single photolysis procedure upon UV irradiation at wavelengths >300 nn. Faster deprotection rates were observed for diNPEOC-protected nucleosides and oligomers than with NVOC-protected ones. The synthesis of pentanucleoside t-Bu-SATE-phosphotriesters d((5')TpCpCpCpTp(3')), d((5')TpApApApAp(3')), and d((5')TpGpGpGpTp(3')) and of dodecanucleoside t-Bu-SATE-phosphotriesters and -phosphorothioate d((5')ApCpApCpCpCpApApTpTpCpTp(3')) and d((5')ApGpApApTpTpGpGpGpTpGpTp(3')) demonstrated the efficiency of the method.