J. J. Strouse et al. / Tetrahedron Letters 46 (2005) 5699–5702
5701
Table 2. Protecteda N1-aryl guanosine derivatives
K.; Ngassa, F. N.; Keeler, J. C.; Dinh, Y. Q. V.; Hilmer, J.
H.; Russon, L. M. Org. Lett. 2000, 2, 927–930; (d) Gerster,
J. F.; Robins, R. K. J. Am. Chem. Soc. 1965, 87, 3752–
3759; (e) Cooper, M. D.; Hodge, R. P.; Tamura, P. J.;
Wilkinson, A. S.; Harris, C. M.; Harris, T. M. Tetrahedron
Lett. 2000, 41, 3555–3558.
O
R
N
N
N
TBSO
NH2
O
N
3. (a) Lakshman, M. K. Curr. Org. Synth. 2005, 2, 83–112;
(b) Hocek, M. Eur. J. Org. Chem. 2003, 245–254; (c)
Brathe, A.; Gundersen, L. L.; Rise, F.; Eriksen, A. B.;
Vollsnes, A. V.; Wang, L. Tetrahedron 1999, 55, 211–
228.
4. Huang, X.; Anderson, K. W.; Zim, D.; Jiang, L.; Klapars,
A.; Buchwald, S. L. J. Am. Chem. Soc. 2003, 125, 6653–
6655.
5. (a) Chan, D. M. T.; Monaco, K. L.; Wang, R. P.; Winters,
M. P. Tetrahedron Lett. 1998, 39, 2933–2936; (b) Evans,
D. A.; Katz, J. L.; West, T. R. Tetrahedron Lett. 1998, 39,
2937–2940; (c) Lam, P. Y. S.; Clark, C. G.; Saubern, S.;
Adams, J.; Winters, M. P.; Chan, D. M. T.; Combs, A.
Tetrahedron Lett. 1998, 39, 2941–2944.
6. (a) Ding, S.; Gray, N. S.; Ding, Q.; Schultz, P. G.
Tetrahedron Lett. 2001, 42, 8751–8755; (b) Bakkestuen, A.
K.; Gundersen, L. L. Tetrahedron Lett. 2003, 44, 3359–
3362; (c) Joshi, R. A.; Patil, P. S.; Muthukrishnan, M.;
Ramana, C. V.; Gurjar, M. K. Tetrahedron Lett. 2004, 45,
195–197; (d) Hari, Y.; Shoji, Y.; Aoyama, T. Tetrahedron
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B.; Arik, L.; Zhang, H.; Fawzi, A. Bioorg. Med. Chem.
Lett. 2005, 15, 2119–2122.
TBSO
OTBS
Entry
1
Compd
R
Yield (%)
46 (61)b
OMe
NO2
17
2
3
4
5
6
18
19
20
21
22
32 (51)b
84 (89)b
53
F
Cl
Br
I
56
7. (a) De Napoli, L.; Messere, A.; Montesarchio, D.;
Piccialli, G. J. Org. Chem. 1995, 60, 2251–2253; (b) De
Napoli, L.; Messere, A.; Montesarchio, D.; Piccialli, G.;
Varra, M. J. Chem. Soc., Perkin Trans. 1 1997, 2079–2082.
8. (a) Maruyama, T.; Sato, Y.; Goto, T.; Fukuhara, M.
Nucleosides Nucleotides 1997, 16, 1079–1082; (b) Maruy-
ama, T.; Kozai, S.; Uchida, M. Nucleosides Nucleotides
1999, 18, 661–671.
43
a TBS = tert-butyldimethylsilyl.
b Yield with 1.1 equiv Cu(OAc)2.
9. (a) Lam, P. Y. S.; Vincent, G.; Clark, C. G.; Deudon, S.;
Jadhav, P. K. Tetrahedron Lett. 2001, 42, 3415–3418; (b)
Mederski, W. W. K. R.; Lefort, M.; Germann, M.; Kux,
D. Tetrahedron 1999, 55, 12757–12770.
In summary, we have described an efficient procedure
for synthesizing novel N1-aryl inosine and guanosine
derivatives. We are currently investigating the anti-viral
activity, metabolism, and toxicological properties of
these compounds.
10. Typical procedure: To an oven dried Schlenk tube were
added the protected nucleoside (0.2 mmol), the boronic
acid (0.4 mmol), anhydrous copper(II) acetate (0.04
˚
mmol), pyridine-N-oxide (0.4 mmol), ground 4 A mole-
cular sieves (ꢀ20 mg), and a stir bar. The tube was sealed
with a septum then evacuated and flushed with oxygen.
Dry pyridine (0.4 mmol) and dichloromethane (2 mL,
dried over molecular sieves) were then added and the
solution was stirred vigorously at room temperature for
24 h. The reaction was then quenched with ammonium
hydroxide in methanol (ꢀ0.05 mL in 1 mL, respectively)
followed by dilution with hexanes (to 50 mL) and washed
with one 25 mL portion each of water, saturated ammo-
nium chloride, 1 M sodium hydroxide, and saturated
sodium chloride. The organics were dried over sodium
sulfate and concentrated in vacuo. Compounds were
purified by medium pressure flash chromatography (Isco
CombiFlash) with methanol/dichloromethane.
Acknowledgments
This research was supported by R21 AI053304 from
NIAID. J.J.S. was supported by NIH/RISE GM61222.
F.T. thanks R25 GM048998 from the MORE Division
of the NIGMS for summer internship support.
References and notes
1. (a) De Clercq, E. Mini-Rev. Med. Chem. 2002, 2, 163–175;
(b) Bishop, A.; Buzko, O.; Heyeck-Dumas, S.; Jung, I.;
Kraybill, B.; Liu, Y.; Shah, K.; Ulrich, S.; Witucki, L.;
Yang, F.; Zhang, C.; Shokat, K. M. Annu. Rev. Biophys.
Biomol. Struct. 2000, 29, 577–606; (c) Galmarini, C. M.;
Mackey, J. R.; Dumontet, C. Lancet Oncol. 2002, 3, 415–
424; (d) Gupta, M.; Nair, V. Tetrahedron Lett. 2005, 46,
1165–1167.
11. Selected data for Table 1: Entry 2, white solid, mp 78 °C
1
(dec), IR (PTFE card, cmꢁ1) 1716; H NMR (400 MHz,
CDCl3) d 8.19, 8.01 (each 1H, s, H-8, H-2), 7.29 (2H, br d,
J = 9.0 Hz), 7.01 (2H, br d, J = 9.0 Hz), 6.00 (1H, d,
J = 4.9 Hz, H-10), 4.50 (1H, m, H-20), 4.30 (1H, m, H-30),
4.13 (1H, m, H-40), 3.98 (1H, m, H-50), 3.85 (3H, s,
–OCH3), 3.79 (1H, m, H-50), 0.95–0.92 (mult. s, 27H),
13
2. (a) Veliz, E. A.; Beal, P. A. J. Org. Chem. 2001, 66, 8592–
8598; (b) Francom, P.; Janeba, Z.; Shibuya, S.; Robins, M.
J. J. Org. Chem. 2002, 67, 6788–6796; (c) Lakshman, M.
0.13–0.14 (mult. s, 18H); C NMR (400 MHz, CDCl3) d
159.9, 156.6, 147.2, 147.1, 138.7, 129.9, 128.3, 124.8, 114.7,
88.1, 85.4, 76.6, 71.7, 62.3, 55.5, TBS signals not listed;