STUDIES ON BASE-BORONATED OLIGONUCLEOTIDES .2.1. INCOMPATIBILITY OF DMT AND CYANOBORANE GROUPS DURING OLIGONUCLEOTIDE SYNTHESIS

The cyanoborane (-BH2CN) nucleosides and nucleotides are a new class o f compounds that mimic natural and synthetic congeners in many ways an d exhibit interesting biochemical and biophysical properties. The B-N bond is isoelectronic with the C-N+ bond of N-7-alkylated 2'-nucleosid es, as well as the C-C bond of naturally occurring 7-alkyl-7-deazanucl eosides. These compounds differ from normal guanosine in that they are incapable of hydrogen bonding at the 7-position. The syntheses of N-7 -cyanoborane 2'-deoxyguanosine, N-2-(dimethylaminomethylene)-N-7-cyano borane 5'-(dimethoxytrityl)-2'-deoxyguanosine (3), and N-2-isobutyryl- N-7-cyanoborane 5'-(dimethoxytrityl)-2'-deoxyguanosine (9) are describ ed. Removal of the dimethoxytrityl (DMT) group from 3 or 9 is accompan ied by significant loss of the cyanoborane moiety. Additionally, dimet hoxytritylation of a cyanoboronated nucleoside leads to partial deboro nation, thus limiting use of the commercially available 5'-DMT nucleos ides as viable precursors in base-boronated oligonucleotide synthesis. The incompatibility of the cyanoborane moiety under DMT removal/addit ion conditions necessitated the search for an alternative method of pr otecting the 5'-hydroxyl of the nucleoside. This paper addresses the p ossible cause of deboronation and describes the synthesis of N-7-cyano boronated nucleosides by a method that avoids transient protection of the sugar hydroxyls.