Stereocontrolled synthesis and nuclear magnetic resonance analysis of boranophosphate/phosphate chimeric oligonucleotides

Abstract

This report describes the stereoselective synthesis of boranophosphate/phosphate (PB/PO) chimeric oligodeoxynucleotides (ODNs) and the nuclear magnetic resonance (NMR) analysis of oligomers containing PB linkages. This stereoselective synthesis involved dimer building blocks containing highly stereopure boranophosphotriester linkages, which enabled the synthesis of PB/PO chimeric ODNs via the standard phosphoramidite method. The stereochemistry of dinucleoside and trinucleoside PBs was confirmed by nuclear Overhauser effect spectroscopy (NOESY) experiments. In the NOESY experiments, the stereochemistry was determined from the correlation of the protons of the borane (BH3) group with those of neighbouring 2'-deoxyribose moieties or nucleobases. Thus, the stereochemistry of the PB linkages within the oligomer was determined, and the stereopurity was also confirmed. A PB linkage was introduced into ODNs with retention of the P-configuration of the dimer building blocks without any loss of stereopurity during solid-phase synthesis. This synthetic approach is expected to be a reliable method for introducing PB linkages with precise stereochemistry. Additionally, detailed analysis of the PB linkages via NMR allowed accurate determination of the stereochemistry.

Keywords

• stereoselective synthesis
• boranophosphate DNA
• nuclear magnetic resonance analysis