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 nm. 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 ‘ T p C p C p C p T p 3 ‘ ), d( 5 ‘ T p A p A p A p A p 3 ‘ ), and d( 5 ‘ T p G p G p G p T p 3 ‘ ) and of dodecanucleoside t -Bu-SATE-phosphotriesters and -phosphorothioate d( 5‘ A p C p A p C p C p C p A p A p T p T p C p T p 3 ‘ ) and d( 5‘ A p G p A p A p T p T p G p G p G p T p G p T p 3‘ ) demonstrated the efficiency of the method.