A novel method for the synthesis of dinucleoside boranophosphates by a boranophosphotriester method.
2'-Deoxyribonucleoside-3'-boranophosphates (nucleotide monomers), including four kinds of nucleobases, were synthesized in good yields by the use of new boranophosphorylating reagents. We have explored various kinds of condensing reagents as well as nucleophilic catalysts for the boranophosphorylation reaction with nucleosides. In the synthesis of dinucleoside boranophosphates, undesirable side reactions occurred at the O-4 of thymine and the O-6 of N2-phenylacetylguanine bases. To avoid these side reactions, additional protecting groups, benzoyl (Bz) and diphenylcarbamoyl (Dpc) groups, were introduced to thymine and guanine bases, respectively. As a result, the condensation reactions proceeded smoothly without any side reactions, and the dimers including four kinds of nucleobases were obtained in excellent yields. In the deprotection of the 5'-DMTr group, Et3SiH was found to be effective as a scavenger for the DMTr cation which caused a P-B bond cleavage. After removal of the other protecting groups by the conventional procedure, four kinds of dinucleoside boranophosphates were obtained in good yields.
Shimizu
Mamoru
M
Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Bioscience Building 702, Kashiwa, Chiba 277-8562, Japan.
Wada
Takeshi
T
Oka
Natsuhisa
N
Saigo
Kazuhiko
K
D001896:Boron Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D007202:Indicators and Reagents; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry
D001896:Boron Compounds; D007202:Indicators and Reagents; D009705:Nucleosides; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; C028270:dinucleoside dimers; D013936:Thymidine