3132
T. Mineno et al. / Tetrahedron Letters 52 (2011) 3131–3132
O
CO2H
CO2H
NHBoc
NH2
Cl
NHBoc
a
b
c
N
N
Cl
N
N
Cl
O
N
Cl
2
3
4
5
O
O
NHBoc
NH2
e
f
d
N
N
N
Cl
N
Cl
O
O
6
7
NH2
NH2
HN
NH2
Cl
g
N
N
N
Cl
8
9
Scheme 1. Synthetic route. Reagents and conditions: (a) Boc2O, DMAP, CH2Cl2, rt, 3 h, 89%; (b) (i) n-BuLi, THF, À78 °C, 1 h; (ii) CO2 excess, 75% in two steps; (c) (i) TFA, CH2Cl2,
rt, 30 min; (ii) phthalic anhydride, AcOH/TFA (10:1), 140 °C, 24 h, 68% in two steps; (d) (i) DPPA, toluene/1,3-dimethyl-2-imidazolidinone (9:1), 140 °C, 2 h; (ii) t-BuOH,
140 °C, overnight, 84% in two steps; (e) TFA, CH2Cl2, rt, 30 min, 97%; (f) 30% CH3NH2 in EtOH, 90 °C, 2 h, 91%; (g) CNBr, EtOH, rt, 1 h, 83%.
stituents of 8 were finally cyclised using CNBr,11 which gave the de-
sired product 9 in a good yield of 83%.
3. Silletti, S.; Kessler, T.; Goldberg, J.; Boger, D. L.; Cheresh, D. A. Proc. Natl. Acad.
Sci. U.S.A. 2001, 98, 119–124.
4. (a) Whittaker, M.; Floyd, C. D.; Brown, P.; Gearing, A. J. H. Chem. Rev. 1999, 99,
In summary, an efficient synthetic sequence for compound 9
was established—the composition of the imidazopyridine scaffold
of fluorescent alkaloid ageladine A. Compound 9 possesses a halo-
gen, one of the functional groups for coupling reactions, at the pyr-
role ring position of ageladine A. This synthetic approach was
designed with versatility in mind to enable structural modifica-
tions for an enhancement of characteristic analysis. The short
and efficient synthetic route introduced here should promote the
versatility of research. Studies of further applications are ongoing.
2735–2776; (b) Matter, A. Drug Discovery Today 2001, 6, 1005–1024.
5. (a) Mineno, T.; Ueno, T.; Urano, Y.; Kojima, H.; Nagano, T. Org. Lett. 2006, 8,
5963–5966; (b) Komatsu, T.; Urano, Y.; Fujikawa, Y.; Kobayashi, T.; Kojima, H.;
Terai, T.; Hanaoka, K.; Nagano, T. Chem. Commun. 2009, 7015–7017; (c)
Komatsu, T.; Kikuchi, K.; Takakusa, H.; Hanaoka, K.; Ueno, T.; Kamiya, M.;
Urano, Y.; Nagano, T. J. Am. Chem. Soc. 2006, 128, 15946–15947; (d) Kojima, H.;
Nanatsubo, N.; Kikuchi, K.; Kawahara, S.; Kirino, Y.; Nagoshi, H.; Hirata, Y.;
Nagano, T. Anal. Chem. 1998, 70, 2446–2453; (e) Shoda, T.; Kikuchi, K.; Kojima,
H.; Urano, Y.; Komatsu, H.; Suzuki, K.; Nagano, T. Analyst 2003, 128, 719–723;
(f) Setsukinai, K.; Urano, Y.; Kakinuma, K.; Majima, H. J. J. Biol. Chem. 2003, 278,
3170–3175; (g) Tobey, S. L.; Anslyn, E. V. Org. Lett. 2003, 5, 2029–2031; (h)
Paradiso, A. M.; Tsien, R. Y.; Machen, T. E. Proc. Natl. Acad. Sci. U.S.A. 1984, 81,
7436–7440; (i) Souto, A. A.; Acuna, A. U.; Andreu, J. M.; Barasoain, I.; Abal, M.;
Amat-Guerri, F. Angew. Chem., Int. Ed. Engl. 1995, 34, 2710–2712.
6. Meketa, M. L.; Weinreb, S. M. Org. Lett. 2006, 8, 1443–1446.
Acknowledgments
7. Shengule, S. R.; Karuso, P. Org. Lett. 2006, 8, 4083–4084.
8. Collin, X.; Robert, J.-M.; Wielgosz, G.; Baut, G. L.; Bobin-Dubigeon, C.; Grimaud,
N.; Petit, J.-Y. Eur. J. Med. Chem. 2001, 36, 639–649.
9. (a) Grunewald, G. L.; Ye, Q. J. Org. Chem. 1988, 53, 4021–4026; (b) Ye, Q.;
Grunewald, G. L. J. Med. Chem. 1989, 32, 478–486.
We are grateful to the Naito Foundation for financial support of
this research. We also thank Professor T. Kunieda (Sojo University)
for his helpful suggestions.
10. Motawia, M. S.; Wengel, J.; Abdel-Megid, A. E. S.; Pedersen, E. B. Synthesis 1989,
384–387.
References and notes
11. (a) Starcevic, K.; Kralj, M.; Ester, K.; Karminski-Zamola, G. Heterocycles 2007,
71, 647–656; (b) Jackson, M. D.; Gould, S. J.; Zabriskie, T. M. J. Org. Chem. 2002,
67, 2934–2941; (c) Rivara, M.; Zuliani, V.; Cocconcelli, G.; Morini, G.; Comini,
M.; Rivara, S.; Mor, M.; Bordi, F.; Barocelli, E.; Ballabeni, V.; Bertoni, S.; Plazzi, P.
V. Bioorg. Med. Chem. 2006, 14, 1413–1424.
1. Fujita, M.; Nakao, Y.; Matsunaga, S.; Seiki, M.; Itoh, Y.; Yamashita, J.; van Soest,
R. W. M.; Fusetani, N. J. Am. Chem. Soc. 2003, 125, 15700–15701.
2. Monsky, W. L.; Kelly, T.; Lin, C. Y.; Yeh, Y.; Stetler-Stevenson, W. G.; Mueller, S.
C.; Chen, W. T. Cancer Res. 1993, 53, 3159–3164.