Aqueous Heck Cross-Coupling Preparation of Acrylate-Modified Nucleotides and Nucleoside Triphosphates for Polymerase Synthesis of Acrylate-Labeled DNA

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• 作者：Jitka Dadov谩 ; Pavl铆na Vidl谩kov谩 ; Radek Pohl ; Lud臎k Havran ; Miroslav Fojta ; Michal Hocek
• 刊名：Journal of Organic Chemistry
• 出版年：2013
• 出版时间：October 4, 2013
• 年：2013
• 卷：78
• 期：19
• 页码：9627-9637
• 全文大小：483K
• 年卷期：v.78,no.19(October 4, 2013)
• ISSN：1520-6904

文摘

Aqueous-phase Heck coupling methodology was developed for direct attachment of butyl acrylate to 5-iodoracil, 5-iodocytosine, 7-iodo-7-deazaadenine, and 7-iodo-7-deazaguanine 2鈥?deoxyribonucleoside 5鈥?O-monophosphates (dNMPs) and 5鈥?O-triphosphates (dNTPs) and compared with the classical approach of phosphorylation of the corresponding modified nucleosides. The 7-substituted 7-deazapurine nucleotides (dA^BAMP, dA^BATP, dG^BAMP, and dG^BATP) were prepared by the direct Heck coupling of nucleotides in good yields (35鈥?5%), whereas the pyrimidine nucleotides reacted poorly and the corresponding BA-modified dNTPs were prepared by triphosphorylation of the modified nucleosides. The acrylate-modified dN^BATPs (N = A, C, and U) were good substrates for DNA polymerases and were used for enzymatic synthesis of acrylate-modified DNA by primer extension, whereas dG^BATP was an inhibitor of polymerases. The butyl acrylate group was found to be a useful redox label giving a strong reduction peak at 鈭?.3 to 鈭?.4 V in cyclic voltammetry.