2',3'-二脱氧-2'-氟-3'-硫代阿拉伯胸苷及其3'-亚磷酰胺衍生物的合成。
Synthesis of 2',3'-dideoxy-2'-fluoro-3'-thioarabinothymidine and its 3'-phosphoramidite derivative.
作者信息
Elzagheid Mohamed I, Tedeschi Anna Lisa, Damha Masad J
机构信息
Department of Chemistry, McGill University, Montreal, Quebec, Canada.
出版信息
Nucleosides Nucleotides Nucleic Acids. 2003 May-Aug;22(5-8):1343-6. doi: 10.1081/NCN-120022961.
An efficient method for the synthesis of 5'-O-monomethoxytrityl-2',3'-dideoxy-2'-fluoro-3'-thioarabinothymidine [(5'MMT)araF-T(3'SH), (5)] and its 3'-phosphoramidite derivative (6) suitable for automated incorporation into oligonucleotides, is demonstrated. A key step in the synthesis involves reaction of 5'-O-MMT-2,3'-O-anhydrothymidine (4) (Eleuteri, A.; Reese, C.B.; Song, Q. J. Chem. Soc. Perkin Trans. 1 1996, 2237 pp.) with sodium thioacetate to give (5'-MMT)araF-T(3'SAc) (5) (Elzagheid, M.I.; Mattila, K.; Oivanen, M.; Jones, B.C.N.M.; Cosstick, Lönnberg, H. Eur. J. Org. Chem. 2000, 1987-1991). This nucleoside was then converted to its corresponding phosphoramidite derivative, 6, as described previously ((a) Sun, S.; Yoshida, A.; Piccirilli, J.A. RNA, 1997, 3, 1352-1363; (b) Matulic-Adamic, J.; Beigelman, L. Helvetica Chemica Acta 1999, 82, 2141-2150: (c) Fettes, K.J.; O'Neil, I.; Roberts, S.M.; Cosstick, R. Nucleosides, Nucleotides and Nucl. Acids 2001, 20, 1351-1354).
展示了一种合成5'-O-单甲氧基三苯甲基-2',3'-二脱氧-2'-氟-3'-硫代阿拉伯胸苷[（5'MMT）araF-T（3'SH），（5）]及其3'-亚磷酰胺衍生物（6）的有效方法，该衍生物适用于自动掺入寡核苷酸。合成中的关键步骤涉及5'-O-MMT-2,3'-O-脱水胸苷（4）（Eleuteri，A.；Reese，C.B.；Song，Q. J. Chem. Soc. Perkin Trans. 1 1996，2237页）与硫代乙酸钠反应生成（5'-MMT）araF-T（3'SAc）（5）（Elzagheid，M.I.；Mattila，K.；Oivanen，M.；Jones，B.C.N.M.；Cosstick，Lönnberg，H. Eur. J. Org. Chem. 2000，1987 - 1991）。然后如前所述将该核苷转化为其相应的亚磷酰胺衍生物6（（a）Sun，S.；Yoshida，A.；Piccirilli，J.A. RNA，1997，3，1352 - 1363；（b）Matulic-Adamic，J.；Beigelman，L. Helvetica Chemica Acta 1999，82，2141 - 2150：（c）Fettes，K.J.；O'Neil，I.；Roberts，S.M.；Cosstick，R. Nucleosides，Nucleotides and Nucl. Acids 2001，20，1351 - 1354）。
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