2ꢁ-Deoxy-2ꢁ-fluoroarabinofuranosyl Purine Nucleosides
1129
1H NMR (DMSO-d6): δ 10.50 (1H, br s), 7.80 (1H, s), 6.54 (2H, br s), 6.13
(1H, dd, J = 4.2 and 16.0 Hz), 5.94 (1H, d, J = 4.5Hz), 5.11 (1H, dt, J =
3.8 and 52.4 Hz), 5.08 (1H, t, J = 5.7 Hz), 4.37 (1H, dd, J = 3.9 and 17.8
Hz), 3.82–3.79 (1H, m), 3.66–3.57 (2H, m); FAB MS (m/z) 286 (M++H).
Anal. Calcd for C10H12FN5O4·0.3H2O: C, 41.33; H, 4.37; N, 24.10. Found:
C, 41.57; H, 4.33; N, 23.69.
REFERENCES
1. a) Damha, M.J.; Wilds, C.J.; Noronha, A.; Brukner, I.; Borkow, G.; Arion, D.; Parniak, M.A. Hybrids
of RNA and arabinonucleic acids (ANA and 2ꢁF-ANA) are substrates of ribonuclease H. J. Am. Chem.
Soc. 1998, 120, 12976–12977; b) Wilds, C.J.; Damha, M.J. 2ꢁ-Deoxy-2ꢁ-fluoro-β-D-arabinonucleosides
and oligonucleotides (2ꢁF-ANA): synthesis and physicochemical studies. Nucleic Acids Res. 2000,
28, 3625–3635 c) Kalota, A.; Karabon, L.; Swider, C.R.; Viazovkina, E.; Eizagheid, M.; Damha,
M.J.; Gewirtz, A.M. 2ꢁ-Deoxy-2ꢁ-fluoro-β-D-arabinonucleic acid (2ꢁF-ANA) modified oligonucleotides
(ON) effect highly efficient, and persistent, gene silencing. Nucleic Acids Res., 2006, 34, 451–461;
d) Dowler, T.; Bergeron, D.; Tedeschi, A.; Paquet, L.; Ferrari, N.; Damha, M.J. Improvements in
siRNA properties mediated by 2ꢁ-deoxy-2ꢁ-fluoro-β-D-arabinonucleic acid (FANA). Nucleic Acids Res.,
2006, 34, 1669–1675.
2. a) Pankeiwicz, K.W.; Krzeminski, J.; Ciszewski, L.A.; Ren, W.-Y.; Watanabe, K.A. A synthesis of 9-
(2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenine and hypoxanthine. An effect of C3ꢁ-endo to C2ꢁ-
endo conformational shift on the reaction course of 2ꢁ-hydroxyl group with DAST. J. Org. Chem.
1992, 57, 553–559 b) Maruyama, T.; Takamatsu, S.; Kozai, S.; Satoh, Y.; Izawa, K. Synthesis of 9-
(2-deoxy-2-fluoro-β-D-arabinofuranosyl)adenine bearing a selectively removable protecting group.
Chem. Pharm. Bull. 1999, 47, 966–970.
3. Marquez, V.E.; Tseng, C.K..-H.; Mitsuya, H.; Aoki, S.; Kelly, J.A.; Ford, Jr., H.; Roth, J.S.; Broder, S.;
Johns, D.G.; Driscoll, J.S. Acid-stable 2ꢁ-fluoro purine dideoxynucleosides as active agents against
HIV. J. Med. Chem. 1990, 33, 978–985.
4. Barchi, J.J.; Marquez, V.E.; Driscoll, J.S.; Ford, Jr., H.; Mitsuya, H.; Shirasaka, T.; Aoki, S.; Kelly, J.A.
Potential anti-AIDS drugs. Lipophilic, adenosine deaminase-activated prodrugs. J. Med. Chem. 1991,
34, 1647–1655.
5. Howell, H.G.; Brodfuehrer, P.R.; Brundidge, S.P.; Benigni, D.A.; Sapino Jr., C. Antiviral nucleosides.
A stereospecific, total synthesis of 2ꢁ-fluoro-2ꢁ-deoxy-β-D-arabinofuranosyl nucleosides. J. Org. Chem.
1988, 53, 85–88.
6. Tennila¨, T.; Azhayeva, E.; Vepsa¨la¨inen, J.; Laatikainen, R.; Azyhayev, A.; Mikhailopulo, I.A. Oligonu-
cleotides containing 9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-adenine and guanine: synthesis, hy-
bridization and antisense properties. Nucleosides Nucleotides Nucleic Acids 2000, 19, 1861–1884.
7. Elzagheid, M.I.; Viazovkina, E.; Damha, M.J.
A new synthesis of 9-(2-deoxy-2-fluoro-β-D-
arabinofuranosyl)guanine (araF-G). Nucleosides Nucleotides Nucleic Acids 2003, 22, 1339–1342.
8. William, E.B.; Brian, E.S.; Brian, B.; Jose, F.P.; William, R.C., Jr.; Dennis, L.; James, G.; Bruce, A.;
Dumitru, I.; Ruichao, G. A new process for antineoplastic agent clofarabine. Org. Process Res. Dev.
2004, 8, 889–896.
9. Krenitsky, T.A.; Koszalka, G.W.; Tuttle, J.V. Purine nucleoside synthesis, an efficient method
employing nucleoside phosphorylases. Biochemistry 1981, 20, 3615–3621.
10. a) Tuttle, J.V.; Krenitsky, T.A. Antiviral nucleoside derivatives and pharmaceutical compositions
containing them. Eur. Pat. Appl. 1988, EP 285432 A2; b) Tuttle, J.V.; Tisdale, M.; Krenitsky, T.A.
Purine 2ꢁ-deoxy-2ꢁ-fluororibosides as antiinfluenza virus agents. J. Med. Chem. 1993, 36, 119–125.
11. a) Siddiqui, M.A.; Discoll, J.S.; Marquez, V.E.; Roth, J.S.; Shirasaka, T.; Mitsuya, H.; Barchi Jr., J.J.; Kel-
ley, J.A. Chemistry and anti-HIV properties of 2ꢁ-fluoro-2ꢁ,3ꢁ-dideoxyarabinofuranosylpyrimidines. J.
Med. Chem., 1992, 35, 2195–2201;. b) Stoeckler, J.D.; Bell, C.A.; Parks, P.E., Jr.; Chu, C.K.; Fox, J.J.;
Ikehara, M. C(2ꢁ)-Substituted purine nucleoside analogs. Interactions with adenosine deaminase
and purine nucleoside phosphorylase and formation of analog nucleotides. Biochem. Pharmacol.
1982, 31, 1723–1728.