Preparation of Short Oligonucleotides via the Phosphoramidite Method Using a Tetrazole Promoter in a Catalytic Manner
1997; American Chemical Society; Volume: 119; Issue: 49 Linguagem: Inglês
10.1021/ja970685b
ISSN1943-2984
AutoresYoshihiro Hayakawa, Masanori Kataoka,
Tópico(s)Synthesis of Tetrazole Derivatives
ResumoA facile phosphoramidite method using a tetrazole promoter in a catalytic manner has been developed for the condensation of a nucleoside 3‘-phosphoramidite and a nucleoside. This method is particularly useful for a large-scale synthesis of short oligonucleotides. For example, dinucleoside phosphates are prepared on a multigram scale in 92−99% yields through the reaction of nucleoside 3‘-N,N-diethylphosphoramidites (1.05 equiv) and 5‘-O-free nucleosides (1.00 equiv) with 5-(p-nitrophenyl)-1H-tetrazole (NPT) (0.05 equiv) in the presence of molecular sieves 13X in acetonitrile (40 °C, 60 min) followed by trimethylsilyl triflate-catalyzed oxidation with bis(trimethylsilyl) peroxide in dichloromethane (40 °C, 10 min). The NPT-catalytic approach is also effective for the synthesis of longer deoxyribonucleotides such as d(5‘CTACCTGT3‘) and 2‘−5‘- or 3‘−5‘-linked ribonucleotides.
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