Synthesis of 2',3'-dideoxy-2'-fluoro-3'-thioarabinothymidine and its 3'-phosphoramidite derivative.
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).
Elzagheid
Mohamed I
MI
Department of Chemistry, McGill University, Montreal, Quebec, Canada.
Tedeschi
Anna Lisa
AL
Damha
Masad J
MJ
D000577:Amides; D001087:Arabinonucleosides / Q000138:chemical synthesis*; D005461:Fluorine; D007202:Indicators and Reagents; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry; D010756:Phosphoric Acids; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis
C479440:2',3'-dideoxy-2'-fluoro-3'-thioarabinothymidine; D000577:Amides; D001087:Arabinonucleosides; D007202:Indicators and Reagents; D009841:Oligonucleotides; D010756:Phosphoric Acids; D005461:Fluorine; C011067:phosphoramidic acid; D013936:Thymidine