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R. Tangirala et al.
LETTER
via a syringe and the reaction mixture was stirred at r.t. for 6.5 h.
The final mixture was poured into brine (10 mL) and extracted with
EtOAc (3 × 10 mL). The combined organic extracts were dried over
MgSO4 and concentrated under reduced pressure. The crude prod-
uct was purified by flash chromatography (1:4 EtOAc–hexane) to
give N-propargylated quinazolinone 6 (81 mg, 66%). 1H NMR (300
MHz, CDCl3): d = 2.35 (t, J = 2.5 Hz, 1 H), 5.08 (d, J = 2.5 Hz, 2
H), 7.50 (ddd, J = 1.2, 7.4, 8.1 Hz, 1 H), 7.62 (dd, J = 0.6, 8.2 Hz, 1
H), 7.75 (ddd, J = 1.6, 7.2, 8.3 Hz, 1 H), 8.24 (dd, J = 1.2, 8.0 Hz, 1
H). 13C NMR (75 MHz, CDCl3): d = 38.2, 72.9, 76.8, 120.3, 126.9,
127.4, 127.7, 134.6, 135.1, 147.0, 160.5. IR (CH2Cl2, NaCl): 3267,
2980, 2361, 2125, 1690, 1577, 1557, 1332, 1152 cm–1. HRMS (EI):
m/z calcd for C11H779BrN2O [M+ – 1]: 261.9742; found: 261.9747.
LRMS (EI): m/z (%) = 262 (46) [M+ – 1], 262 (46) [M+ +1], 183
(100), 155 (20), 129 (31), 102 (19), 63 (14).
(5) (a) Yadav, J. S.; Reddy, B. V. S. Tetrahedron Lett. 2002, 43,
1905. (b) Wang, H.; Ganesan, A. Tetrahedron Lett. 1998,
39, 9097. (c) Kelly, R. T.; Chamberland, S.; Silva, R. A.
Tetrahedron Lett. 1999, 40, 2723. (d) Molina, P.; Tárraga,
A.; Gonzalez-Tejero, A. Synthesis 2000, 1523. (e) Toyota,
M.; Komori, C.; Ihara, M. Heterocycles 2002, 56, 101.
(f) Harayama, T.; Morikami, Y.; Shigeta, Y.; Abe, H.;
Takeuchi, Y. Synlett 2003, 847. (g) Chavan, S. P.; Sivappa,
R. Tetrahedron 2004, 60, 9931. (h) Harayama, T.; Hori, A.;
Serban, G.; Morikami, Y.; Matsumoto, T.; Abe, H.;
Takeuchi, Y. Tetrahedron 2004, 60, 10645. (i) Ma, Z.;
Hano, Y.; Nomura, T.; Chen, Y. Bioorg. Med. Chem. Lett.
2004, 14, 1193. (j) Twin, H.; Batey, R. A. Org. Lett. 2004, 6,
4913. (k) Bowman, W. R.; Cloonan, M. O.; Fletcher, A. J.;
Stein, T. Org. Biomol. Chem. 2005, 3, 1460.
(6) (a) Cagir, A.; Jones, S. H.; Eisenhauer, B. M.; Gao, R.;
Hecht, S. M. Bioorg. Med. Chem. Lett. 2004, 14, 2051.
(b) Cagir, A.; Eisenhauer, B. M.; Gao, R.; Thomas, S. J.;
Hecht, S. M. Bioorg. Med. Chem. 2004, 12, 6287.
(7) Dallavalle, S.; Merlini, L.; Beretta, G. L.; Tinelli, S.; Zunino,
F. Bioorg. Med. Chem. Lett. 2004, 14, 5757.
General Procedure for the Synthesis of Luotonins
A solution of N-propargylated quinazolinone 6 in benzene was add-
ed to a 15 × 45 mm cylindrical screw-cap glass vial. The appropri-
ate isonitrile followed by hexamethylditin were added at r.t. The
vial was capped and the reaction mixture was irradiated with a 275
W GE sunlamp for 8 h. The solvent was then evaporated and the res-
idue was purified by column chromatography (1:9 acetone–CH2Cl2
or 1:9 EtOAc–CH2Cl2) to give luotonins as pale yellow to tan solids.
(8) (a) Curran, D. P.; Liu, H. J. Am. Chem. Soc. 1992, 114,
5863. (b) Curran, D. P.; Ko, S. B.; Josien, H. Angew. Chem.,
Int. Ed. Engl. 1995, 34, 2683. (c) Curran, D. P.; Liu, H.;
Josien, H.; Ko, S. B. Tetrahedron 1996, 52, 11385.
(d) Josien, H.; Bom, D.; Curran, D. P.; Zheng, Y.-H.; Chou,
T.-C. Bioorg. Med. Chem. Lett. 1997, 7, 3189. (e) Josien,
H.; Ko, S. B.; Bom, D.; Curran, D. P. Chem.–Eur. J. 1998,
4, 67. (f) Curran, D. P.; Josien, H.; Bom, D.; Gabarda, A.;
Du, W. In The Camptothecins: Unfolding their Anticancer
Potential, Vol. 922; Liehr, J. G.; Giovanella, B. C.;
Verschraegen, C. F., Eds.; NY Acad. Sci.: New York, 2000,
112–121. (g) Gabarda, A. E.; Du, W.; Isarno, T.; Tangirala,
R. S.; Curran, D. P. Tetrahedron 2002, 58, 6329.
(h) Gabarda, A. E.; Curran, D. P. J. Comb. Chem. 2003, 5,
617.
Acknowledgment
We thank the National Institutes of Health for funding this work.
References
(1) Ma, Z. Z.; Hano, Y.; Nomura, T.; Chen, Y.-J. Heterocycles
1997, 46, 541.
(2) Recent reviews on synthesis and medicinal chemistry of
camptothecins: (a) Thomas, C. J.; Rahier, N. J.; Hecht, S. M.
Bioorg. Med. Chem. 2004, 12, 1585. (b) Du, W.
(9) Representative experiments are provided at the end of the
paper. Complete details and characterization data are in:
Tangirala, R. PhD Thesis; University of Pittsburgh:
Pittsburgh, 2005.
(10) Liu, H.; Ko, S. B.; Josien, H.; Curran, D. P. Tetrahedron
Lett. 1995, 36, 8917.
Tetrahedron 2003, 59, 8649. (c) Pizzolato, J. F.; Saltz, L. B.
Lancet 2003, 361, 2235. (d) Ulukan, H.; Swaan, P. Drugs
2002, 62, 2039. (e) Kim, D.-K.; Lee, N. Mini-Rev. Med.
Chem. 2002, 2, 611. (f) Lerchen, H.-G. Drugs Fut. 2002, 29,
869. (g) Zunino, F.; Dallavalle, S.; Laccabue, D.; Beretta,
G.; Merlini, L.; Pratesi, G. Curr. Pharm. Design 2002, 8,
2505.
(11) Allen, C. F. H.; Vanallen, J. A. Org. Synth., Coll. Vol. III;
Wiley: New York, 1965, 275.
(3) Cagir, A.; Jones, S. H.; Gao, R.; Eisenhauer, B. M.; Hecht,
S. M. J. Am. Chem. Soc. 2003, 125, 13628.
(12) Antony, S.; Jayaraman, M.; Laco, G.; Kohlhagen, G.; Kohn,
K. W.; Cushman, M.; Pommier, Y. Cancer Res. 2003, 63,
7428.
(4) (a) Du, W.; Curran, D. P.; Bevins, R. L.; Zimmer, S. G.;
Zhang, J.; Burke, T. G. Bioorg. Med. Chem. 2002, 10, 103.
(b) Laco, G. S.; Du, W.; Kohlhagen, G.; Sayer, J. M.; Jerina,
D. M.; Burke, T. G.; Curran, D. P.; Pommier, Y. Bioorg.
Med. Chem. 2004, 12, 5225. (c) Hautefaye, P.; Cimetière,
B.; Pierre, A.; Léonce, S.; Hickman, J.; Laine, W.; Bailly, C.;
Lavelle, G. Bioorg. Med. Chem. Lett. 2003, 13, 2731.
Synlett 2005, No. 18, 2843–2846 © Thieme Stuttgart · New York