o-Chlorobenzoyl Protected Nucleoside Succinates for Functionalization of the Solid Support Used in Oligoribonucleotide Synthesis

Abstract

In the final stages of automated oligonucleotide synthesis the oligomer has to be cleaved from the solid support. This is usually carried out using ammonolysis since the 3′-end of the oligomer is most commonly attached to the support via a succinate ester linkage. The t-butyldimethylsilyl (TBDMS) group is currently the most widely used 2′-hydroxyl in RNA-synthesis and is used together with phosphoroamidites¹ as well as with H-phosphonates². The nucleoside directly attached to the support, often carries the same TBDMS-protection on the secondary hydroxyl next to the succinate linker. The use of more labile acyl groups for N-protection in RNA-synthesis was suggested in reports where partial loss of the TBDMS groups during ammonolysis was detected^3,4. This has since been introduced^5,6 and is now general practice. However, one can question if all oligomer will be released from the support under the milder ammonolytic conditions used to remove these more labile N-protecting groups.