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

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.