Formation of N -Branched Oligonucleotides as By-products in Solid-Phase Oligonucleotide Synthesis

Abstract

During the synthesis of oligonucleotides by the standard phosphoramidite method using 2′-deoxycytidine- derivatized solid support, a side reaction was observed that gave rise to the formation of high molecular weight N-branched oligomers having two identical chains linked to the 3′-terminal 2′-deoxycytidine.Postsynthesis treatment with neat triethylamine trihydrofluoride selectively cleaved the phosphoramidate linkage and converted the N-branched oligomers back to the expected oligonucleotides.