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

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 stereo...

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Main Authors: Kiyoshi Kakuta, Taiichi Sakamoto, Hajime Sato, Kazuki Sato, Takeshi Wada
Format: Article
Language:English
Published: The Royal Society 2025-04-01
Series:Royal Society Open Science
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Online Access:https://royalsocietypublishing.org/doi/10.1098/rsos.241797
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author Kiyoshi Kakuta
Taiichi Sakamoto
Hajime Sato
Kazuki Sato
Takeshi Wada
author_facet Kiyoshi Kakuta
Taiichi Sakamoto
Hajime Sato
Kazuki Sato
Takeshi Wada
author_sort Kiyoshi Kakuta
collection DOAJ
description 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.
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spelling doaj-art-02aed5797f344631b3eb4a91eb04a9cd2025-08-20T03:06:06ZengThe Royal SocietyRoyal Society Open Science2054-57032025-04-0112410.1098/rsos.241797Stereocontrolled synthesis and nuclear magnetic resonance analysis of boranophosphate/phosphate chimeric oligonucleotidesKiyoshi Kakuta0Taiichi Sakamoto1Hajime Sato2Kazuki Sato3Takeshi Wada4Department of Medicinal and Life Sciences, Tokyo University of Science, Noda, Chiba, JapanDepartment of Life Science, Chiba Institute of Technology, Narashino, Chiba, JapanBioSpin Division, Bruker Japan K.K., Yokohama, Kanagawa, JapanDepartment of Medicinal and Life Sciences, Tokyo University of Science, Noda, Chiba, JapanDepartment of Medicinal and Life Sciences, Tokyo University of Science, Noda, Chiba, JapanThis 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.https://royalsocietypublishing.org/doi/10.1098/rsos.241797stereoselective synthesisboranophosphate DNAnuclear magnetic resonance analysis
spellingShingle Kiyoshi Kakuta
Taiichi Sakamoto
Hajime Sato
Kazuki Sato
Takeshi Wada
Stereocontrolled synthesis and nuclear magnetic resonance analysis of boranophosphate/phosphate chimeric oligonucleotides
Royal Society Open Science
stereoselective synthesis
boranophosphate DNA
nuclear magnetic resonance analysis
title Stereocontrolled synthesis and nuclear magnetic resonance analysis of boranophosphate/phosphate chimeric oligonucleotides
title_full Stereocontrolled synthesis and nuclear magnetic resonance analysis of boranophosphate/phosphate chimeric oligonucleotides
title_fullStr Stereocontrolled synthesis and nuclear magnetic resonance analysis of boranophosphate/phosphate chimeric oligonucleotides
title_full_unstemmed Stereocontrolled synthesis and nuclear magnetic resonance analysis of boranophosphate/phosphate chimeric oligonucleotides
title_short Stereocontrolled synthesis and nuclear magnetic resonance analysis of boranophosphate/phosphate chimeric oligonucleotides
title_sort stereocontrolled synthesis and nuclear magnetic resonance analysis of boranophosphate phosphate chimeric oligonucleotides
topic stereoselective synthesis
boranophosphate DNA
nuclear magnetic resonance analysis
url https://royalsocietypublishing.org/doi/10.1098/rsos.241797
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AT taiichisakamoto stereocontrolledsynthesisandnuclearmagneticresonanceanalysisofboranophosphatephosphatechimericoligonucleotides
AT hajimesato stereocontrolledsynthesisandnuclearmagneticresonanceanalysisofboranophosphatephosphatechimericoligonucleotides
AT kazukisato stereocontrolledsynthesisandnuclearmagneticresonanceanalysisofboranophosphatephosphatechimericoligonucleotides
AT takeshiwada stereocontrolledsynthesisandnuclearmagneticresonanceanalysisofboranophosphatephosphatechimericoligonucleotides