Acid/Azole Complexes as Highly Effective Promoters in the Synthesis of DNA and RNA Oligomers via the Phosphoramidite Method

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• 作者：Yoshihiro Hayakawa ; Rie Kawai ; Akiyoshi Hirata ; Jun-ichiro Sugimoto ; Masanori Kataoka ; Akira Sakakura ; Masaaki Hirose ; and Ryoji Noyori
• 刊名：Journal of the American Chemical Society
• 出版年：2001
• 出版时间：August 29, 2001
• 年：2001
• 卷：123
• 期：34
• 页码：8165 - 8176
• 全文大小：169K
• 年卷期：v.123,no.34(August 29, 2001)
• ISSN：1520-5126

文摘

The utility of various kinds of acid salts of azole derivatives as promoters for the condensation ofa nucleoside phosphoramidite and a nucleoside is investigated. Among the salts, N-(phenyl)imidazolium triflate,N-(p-acetylphenyl)imidazolium triflate, N-(methyl)benzimidazolium triflate, benzimidazolium triflate, andN-(phenyl)imidazolium perchlorate have shown extremely high reactivity in a liquid phase. These reagentsserve as powerful activators of deoxyribonucleoside 3'-(allyl N,N-diisopropylphosphoramidite)s or 3'-(2-cyanoethyl N,N-diisopropylphosphoramidite)s employed in the preparation of deoxyribonucleotides, and 3'-O-(tert-butyldimethylsilyl)ribonucleoside 2'-(N,N-diisopropylphosphoramidite)s or 2'-O-(tert-butyldimethylsilyl)ribonucleoside 3'-(N,N-diisopropylphosphoramidite)s used for the formation of 2'-5' and 3'-5' internucleotidelinkages between ribonucleosides, respectively. The azolium salt has allowed smooth and high-yield condensationof the nucleoside phosphoramidite and a 5'-O-free nucleoside, in which equimolar amounts of the reactantsand the promoter are employed in the presence of powdery molecular sieves 3A in acetonitrile. It has beenshown that some azolium salts serve as excellent promoters in the solid-phase synthesis of oligodeoxyribonucleotides and oligoribonucleotides. For example, benzimidazolium triflate and N-(phenyl)imidazolium triflatecan be used as effective promoters in the synthesis of an oligodeoxyribonucleotide, ^5'CGACACCCAATTCTGAAAAT^3' (20mer), via a method using O-allyl/N-allyloxycarbonyl-protected deoxyribonucleoside 3'-phosphoramidites or O-(2-cyanoethyl)/N-phenoxyacetyl-protected deoxyribonucleotide 3'-phosphoramidite asbuilding blocks, respectively, on high-cross-linked polystyrene resins. Further, N-(phenyl)imidazolium triflateis useful for the solid-phase synthesis of oligoribonucleotides, such as ^5'AGCUACGUGACUACUACUUU^3'(20mer), according to an allyl/allyloxycarbonyl-protected strategy. The utility of the azolium promoter hasbeen also demonstrated in the liquid-phase synthesis of some biologically important substances, such as cytidine-5'-monophosphono-N-acetylneuraminic acid (CMP-Neu5Ac) and adenylyl(2'-5')adenylyl(2'-5')adenosine(2-5A core).