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LETTER
(19) Selected Physicochemical Data for Compound 7
(2) (a) Applied Antisense Oligonucleotide Technology; Stein,
C. A.; Krieg, A. M., Eds.; Wiley-Liss: New York, 1998.
(b) Lee, L. K.; Roth, C. M. Curr. Opin. Biotechnol. 2003, 14,
505. (c) Crooke, S. T. Annu. Rev. Med. 2004, 55, 61.
(d) Van Aerschot, A. Antiviral Res. 2006, 71, 307.
(e) Rayburn, E. R.; Zhang, R. Drug Discov. Today 2008, 13,
513. (f) Seth, P. P.; Siwkowski, A.; Allerson, C. R.;
Vasquez, G.; Lee, S.; Prakash, T. P.; Wancewicz, E. V.;
Witchell, D. J. Med. Chem. 2009, 52, 10; and cited literature.
(3) Sorbera, L. A.; Rabasseda, X.; Castaner, J. Drugs Future
1998, 23, 1168.
(4) For reviews on this topic, see: (a) De Mesmaeker, A.;
Häner, R.; Martin, P.; Moser, H. E. Acc. Chem. Res. 1995,
28, 366. (b) Kurreck, J. Eur. J. Biochem. 2003, 270, 1628.
(c) Aboul-Fadl, T. Curr. Med. Chem. 2005, 12, 763.
(d) Seth, P. P.; Siwkowski, A.; Allerson, C. R.; Vasquez, G.;
Lee, S.; Prakash, T. P.; Wancewicz, E. V.; Witchell, D.;
Swayze, E. E. J. Med. Chem. 2009, 52, 10; and cited
literature. (e) For a very interesting discussion in several
aspects of nucleic acids research in the different areas,
including antisense oligonucleotides, see: Hecht, S. M.
J. Am. Chem. Soc. 2009, 131, 3791.
1H NMR (400 MHz, CDCl3): d = 1.99 (s, 9 H, t-Bu), 1.82–
1.92 (m, 1 H, H2¢¢), 1.89 (s, 3 H, CH3), 2.39 (ddd, 1 H,
J = 10.0, 6.5, 3.0 Hz, H2¢), 4.20 (ddd, 1 H, J = 10.0, 3.0 Hz,
H3¢), 4.24 (m, 1 H, H4¢), 6.23 (br s, 2 H, H5¢ and H6¢), 6.34 (dd,
1 H, J = 6.5 Hz, H1¢), 6.93 (d, 1 H, J = 1.0 Hz, H6), 7.38–7.50
(m, 6 H, Har), 7.59–7.67 (m, 4 H, Har), 9.28 (br s, 1 H, NH)
ppm. 13C NMR (100 MHz, CDCl3): d = 12.6 (CH3, CH3),
18.9 (C, t-Bu), 26.8 (CH3, t-Bu), 39.6 (CH, C2¢), 75.4 (CH,
C3¢), 80.7 (CH, C6¢), 84.8 (CH, C1¢), 88.2 (CH, C4¢), 111.3 (C,
C5), 127.9, 128.0 (CH, Car), 130.2 (CH, Car), 132.7 (C, Car),
134.9 (CH, C6), 135.6, 135.8 (CH, Car), 142.1 (CH, C5¢),
150.2 (C, C=O), 163.6 (C, C=O) ppm. MS (CI/NH3): m/z
(C27H31I N2O4Si) = 620 [M + NH4 ], 603 [M + H+].
+
(20) Takai, K.; Nitta, K.; Utimoto, K. J. Am. Chem. Soc. 1986,
108, 7408.
(21) For recent examples, see: (a) Van Daele, I.; Munier-
Lehmann, H.; Froeyen, M.; Balzarini, J.; Van Calenbergh, S.
J. Med. Chem. 2007, 50, 5281. (b) Nuzzi, A.; Massi, A.;
Dondoni, A. QSAR Comb. Sci. 2007, 26, 1191.
(22) Sanghvi, Y. S.; Bharadwaj, R.; Debart, F.; De Mesmaeker,
A. Synthesis 1994, 1163.
(5) (a) De Mesmaeker, A.; Lebreton, J.; Waldner, A. WO 92/
20,823, 1992; Chem. Abstr. 1993, 118, 192190m. (b) De
Mesmaeker, A.; Lebreton, J.; Waldner, A.; Bévièrre, M.-O.;
Lesueur, C. WO 95/20,597, 1995; Chem. Abstr. 1996, 124,
202954d.
(6) For a review on amide substituted oligodeoxynucleotide
analogues, see: De Mesmaeker, A.; Waldner, A.; Lebreton,
J.; Fritsch, V.; Wolf, R. M. In Carbohydrate Modifications
in Antisense Research; Sanghvi, Y. S.; Cook, P. D., Eds.;
ACS Symposium Series 580, ACS: Washington DC, 1994,
24–39.
(23) (a) Hanessian, S.; Giroux, S.; Larsson, A. Org. Lett. 2006, 8,
5481. (b) See also: Wipf, P.; Spencer, S. R. J. Am. Chem.
Soc. 2005, 127, 225.
(24) For initial work on this transformation, see: (a) Chu, C. K.;
Doboszewski, B.; Schmidt, W.; Ullas, G. V.; Van Roey, P.
J. Org. Chem. 1989, 54, 2767. For recent examples, see:
(b) See ref. 8. (c) Li, X.; Zhan, Z.-Y. J.; Knipe, R.; Lynn,
D. G. J. Am. Chem. Soc. 2002, 124, 747. For an interesting
discussion on C-3¢ radical allylation on thymidine, see:
(d) Horton, D.; Chen, K.; No, Z.; Lee, H. C. Carbohydr. Res.
2007, 342, 259.
(7) For more work in this field, see: De Mesmaeker, A.;
Lebreton, J.; Jouanno, C.; Fritsch, V.; Wolf, R. M.;
Wendeborn, S. Synlett 1997, 1287; and cited literature.
(8) Rozners, E.; Katkevica, D.; Bizdena, E.; Strömberg, R.
J. Am. Chem. Soc. 2003, 125, 12125.
(9) Whelan, J. Drug Discov. Today 2005, 10, 1014.
(10) Wendeborn, S.; Wolf, R.; De Mesmaeker, A. Tetrahedron
Lett. 1995, 36, 6879.
(25) Selected Physicochemical Data for Compound 6
1H NMR (400 MHz, CDCl3): d = 0.70–0.80 (15 H, 3 CH3
and 3 CH2, CH3 and CH2 n-Bu), 1.02 (s, 9 H, 3 CH3, t-Bu),
1.10–1.27 (m, 6 H, 3 CH2, n-Bu), 1.38 (m, 6 H, 3 CH2, n-Bu),
2.26 (m, 1 H, H2¢), 2.40 (m, 1 H, H2¢), 2.40 (s, 3 H, CH3), 3.14
(m, 1 H, H3¢), 3.75–3.86 (m, 2 H, H4¢ and H5¢), 4.11 (m, 1 H,
H5¢), 5.76 (dd, 1 H, J = 7.0, 19.0 Hz, H3¢¢), 6.15 (d, 1 H,
J = 19.0 Hz, H3¢¢¢), 6.16 (dd, 1 H, J = 3.0, 7.0 Hz, H1¢), 7.22–
7.49 (m, 6 H, Har), 7.66 (s, 1 H, H6), 7.62–7.84 (m, 4 H, Har),
9.50 (s, 1 H, NH) ppm. 13C NMR (100 MHz, CDCl3): d = 9.4
(CH2, n-Bu), 11.9 (CH3, CH3), 13.6 (CH3, n-Bu), 19.4 (C, t-
Bu), 27.1 (CH3, t-Bu), 27.4 (CH2, n-Bu), 29.0 (CH2, n-Bu),
39.3 (CH2, C2¢), 45.0 (CH, C3¢), 62.5 (CH2, C5¢), 84.7 (CH,
C1¢), 85.6 (CH, C4¢), 110.5 (C, C5), 127.8 (CH, Car), 129.8
(CH, Car), 132.5 (CH, C3¢¢¢), 132.8, 133.3 (C, Car), 135.2,
135.4 (CH, Car), 135.6 (CH, C6), 145.5 (CH, C3¢¢), 150.5
(C=O), 164.2 (C=O) ppm. ESI-HRMS: m/z [M + H+] calcd
for C40H61N2O4SiSn [M(119Sn) + H]+: 780.3433; found:
780.3431.
(11) (a) Lebreton, J.; De Mesmaeker, A.; Waldner, A. Synlett
1994, 54. (b) De Mesmaeker, A.; Waldner, A.; Sanghvi,
Y. S.; Lebreton, J. Bioorg. Med. Chem. Lett. 1994, 4, 395.
(12) Sharma, R. A.; Bobeck, M. J. Org. Chem. 1978, 43, 367.
(13) De Mesmaeker, A., Lebreton, J. 1992, unpublished results.
(14) (a) Muller, S.; Liepold, B.; Roth, G. J.; Bestmann, H. J.
Synlett 1996, 521. (b) Ohira, S. Synth. Commun. 1989, 19,
561. The Bestmann–Ohira reagent is prepared by treatment
of dimethyl(2-oxopropyl)phosphonate with tosylazide in the
presence of NaH followed by purification on silica gel
chromatography, see: (c) Callant, P.; D’Haenens, L.;
Vandewalle, M. Synth. Commun. 1984, 14, 155.
(15) Wnuk, S. F.; Robins, M. J. Can. J. Chem. 1993, 71, 192.
(16) (a) Wnuk, S. F.; Yuan, C.-S.; Borchardt, R. T.; Balzarini, J.;
De Clercq, E.; Robins, M. J. J. Med. Chem. 1994, 37, 3579.
(b) Wnuk, S. F.; Ro, B.-O.; Valdez, C. A.; Lewandowska, E.;
Valdez, N. X.; Sacasa, P. R.; Yin, D.; Zhang, J.; Borchardt,
R. T.; De Clercq, E. J. Med. Chem. 2002, 45, 2651.
(c) Rapp, M.; Haubrich, T. A.; Perrault, J.; Mackey, Z. B.;
McKerrow, J. H.; Chiang, P. K.; Wnuk, S. F. J. Med. Chem.
2006, 49, 2096.
(26) For a general review, see: Espinet, P.; Echavarren, A. M.
Angew. Chem. Int. Ed. 2004, 43, 4704; and references cited
therein.
(27) Selected Physicochemical Data for Compound 8
1H NMR (400 MHz, CDCl3): d = 1.09 (s, 9 H, t-Bu), 1.10 (s,
9 H, t-Bu), 1.58 (s, 3 H, CH3A), 1.86 (s, 3 H, CH3B), 2.44–
2.19 (m, 4 H, H2¢A and H2¢B), 3.18–3.02 (tdd, 1 H, J = 8.0,
8.0, 8.0 Hz, H3¢A), 3.79 (m, 1 H, H4¢A), 3.75 (dd, part A of an
AB system, 1 H, J = 12.0, 3.0 Hz, H5¢A), 4.13–4.03 (dd, part
B of an AB system, 1 H, J = 12.0, 3.0 Hz, H5¢A), 4.22–4.14
(1 H, dt, J = 6.0, 3.0 Hz, H4¢B), 4.42–4.33 (dd, 1 H, J = 7.0,
4.0 Hz, H3¢B), 5.34–5.21 (m, 1 H, Hd), 5.52–5.38 (m, 1 H,
Ha), 6.05–5.90 (2 dd, 2 H, J = 8.0 Hz, Hb and Hc), 6.19–6.09
(dd, 1 H, J = 4.0, 7.0 Hz, H1¢A), 6.40–6.30 (dd, 1 H, J = 7.0
Hz, H1¢B), 7.00 (s, 1 H, H6B), 7.49–7.27 (m, 12 H, Har), 7.51
(17) Jung, P. M. J.; Burger, A.; Biellmann, J.-F. J. Org. Chem.
1997, 62, 8309.
(18) Thibonnet, J.; Abarbri, M.; Parrain, J.-L.; Duchêne, A.
Tetrahedron 2003, 56, 4433.
Synlett 2009, No. 20, 3341–3345 © Thieme Stuttgart · New York