Studies on base-boronated oligonucleotides. 2 (1). Incompatibility of DMT and cyanoborane groups during oligonucleotide synthesis.

Abstract

The cyanoborane (-BH2CN) nucleosides and nucleotides are a new class of compounds that mimic natural and synthetic congeners in many ways and exhibit interesting biochemical and biophysical properties. The B-N bond is isoelectronic with the C-N+ bond of N7-alkylated 2'-nucleosides, as well as the C-C bond of naturally occurring 7-alkyl-7-deazanucleosides. These compounds differ from normal guanosine in that they are incapable of hydrogen bonding at the 7-position. The syntheses of N7-cyanoborane 2'-deoxyguanosine, N2-(dimethylaminomethylene)-N7-cyanoborane 5'-(dimethoxytrityl)-2'-deoxyguanosine (3), and N2-isobutyryl-N7-cyanoborane 5'-(dimethoxytrityl)-2'-deoxyguanosine (9) are described. Removal of the dimethoxytrityl (DMT) group from 3 or 9 is accompanied by significant loss of the cyanoborane moiety. Additionally, dimethoxytritylation of a cyanoboronated nucleoside leads to partial deboronation, thus limiting use of the commercially available 5'-DMT nucleosides as viable precursors in base-boronated oligonucleotide synthesis. The incompatibility of the cyanoborane moiety under DMT removal/addition conditions necessitated the search for an alternative method of protecting the 5'-hydroxyl of the nucleoside. This paper addresses the possible cause of deboronation and describes the synthesis of N7-cyanoboronated nucleosides by a method that avoids transient protection of the sugar hydroxyls.