Individual Isomers of Dinucleoside Boranophosphates as Synthons for Incorporation into Oligonucleotides: Synthesis and Configurational Assignment

Abstract

Individual isomers of the protected boranophosphates 5a and 5b, i.e., the N⁶-benzyl-2′-deoxy-5′-O-(4,4′-dimethoxytrityl)adenosin-3′-yl 2′-deoxy-4-O-(4-nitrophenyl)uridin-5′-yl boranophosphates, were synthesized via stereospecific silylation and boronation of their H-phosphonate precursors. 2D-NMR Spectroscopic studies yielded an initial assignment of the isomer configuration, which was further confirmed unambiguously by a parallel chemical synthesis. Deprotection of the `dimers' 5a and 5b yielded the individual [P(R)]- and [P(S)]-isomers 7a and 7b, respectively, i.e., the 2′-deoxyadenosin-3′-yl 2′-deoxycytidin-5′-yl boranophosphates. Their substrate properties toward phosphodiesterase I were identical to those of the previously characterized isomers of dithymidine boranophosphate. The protected `dimers' 5a and 5b can be used as synthons to incorporate the boranophosphate linkage with a defined configuration to selected positions of an oligonucleotide chain.