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 N- 6-benzyl-2'-deoxy-5'- O-(4,4'-dimethoxytrityl)adenosin-3'-yl 2'-deoxy-4-O-( 4-nitrophenyl)uridin-5'-yl boranophosphates, were synthesized via stereospe cific silylation and boronation of their H-phosphonate precursors. 2D-NMR S pectroscopic studies yielded an initial assignment of the isomer configurat ion, which was further confirmed unambiguously by a parallel chemical synth esis. 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 towar d phosphodiesterase I were identical to those of the previously characteriz ed isomers of dithymidine boranophosphate. The protected 'dimers' 5a and Sb can be used as synthons to incorporate the boranophosphate linkage with a defined configuration to selected positions of an oligonucleotide chain.