LETTER
Synthesis of Luotonin B and E
87
(2) Ali, M. M.; Tasneem, K. C.; Rajanna, P. K.; Sai Prakash
Synlett 2001, 251.
(3) (a) Amin, A. H.; Mehta, D. R.; Samarth, S. G. Prog. Drug
Res. 1970, 14, 218. (b) Johne, S. Prog. Drug Res. 1982, 26,
259.
off, and further purified by column chromatography using
EtOAc and hexane (7:3) to yield the lutonin B. The filtrate
was diluted with H2O, and extracted with EtOAc, and dried.
Concentration and purification by column chromatography
yielded 11.
(4) Cagir, A.; Jones, S. H.; Gao, R.; Eisenhauer, B. M.; Hecht,
S. M. J. Am. Chem. Soc. 2003, 125, 13628.
(16) To a suspension of cyanoaldehyde (1 g, 0.5 mmol, 1 equiv)
in AcOH (10 mL) and Ac2O (0.2 mL), methyl anthranilate
(0.554 g, 0.71 mmol, 1.5 equiv) was added, and the reaction
mixture was heated to reflux for a period of 12–14 h. The
reaction mass was then cooled to r.t., and precipitated
product was filtered off. The mother liquor was then diluted
with H2O, and extracted with EtOAc. The precipitated
product mixture and the EtOAc extracts were combined
together, concentrated under vacuum. The product was then
purified by column chromatography using EtOAc and
hexane (7:3), and pure luotonin B was isolated as white to
off-white solid in 0.890 g, 54% of yield. Also 12% of 11 was
also isolated from the column.
(17) Methyl-2-(11-oxo-11,13-dihydroquinolino[2¢,3¢:3,4]-
pyrrolo[2,1-b]quinazolin-13-yl)amino benzoate (11)
Yield 20%; mp 312–314 °C. 1H NMR (400 MHz, CDCl3):
d = 3.80 (s, 3 H), 6.77 (t, J = 7.2 Hz, 1 H), 7.26 (s, 1 H), 7.27
(s, 1 H), 7.35 (t, J = 7.6 Hz, 1 H), 7.52 (t, J = 6.8 Hz, 1 H),
7.69 (t, J = 7.6 Hz, 1 H), 7.80–7.97 (m, 4 H), 8.1 (d, J = 8.0
Hz, 1 H), 8.34 (dd, J = 1.6, 7.8 Hz, 1 H), 8.48 (s, 1 H) 8.52
(d, J = 8.8 Hz, 1 H), 8.85 (d, J = 9.6 Hz, 1 H). 13C NMR (400
MHz, CDCl3): d = 51.8, 68.4, 112, 113.6, 117.6, 122.4,
126.7, 127.6, 128.4, 128.6, 128.8, 129.1, 130.8, 131.2,
131.7, 132.2, 132.6, 134.4, 134.6, 148.0, 149.0, 150.0,
150.4, 151.4, 160.6, 168.9. MS: m/z (%) = 435 [M + 1],
302.2, 137.1. Anal Calcd for C26H18N4O3: C, 71.88; H, 4.18;
N, 12.90. Found: C, 71.86; H, 4.15; N, 12.87.
(5) (a) Zhao, H.; Lee, C.; Sai, P.; Choe, Y. H.; Boro, M.; Pendri,
A.; Guan, S.; Greenwald, R. B. J. Org. Chem. 2000, 65,
4601. (b) Fassberg, J.; Stella, V. J. J. Pharm. Sci. 1992, 81,
676. (c) Burke, T. G.; Mi, Z. Anal. Biochem. 1993, 212, 285.
(d) Burke, T. G.; Mi, Z. J. Med. Chem. 1994, 37, 40.
(6) (a) Suresh Babu, M.; Raghunadh, A.; Anil Kumar, N.;
Syam Kumar, U. K.; Vasu Dev, R.; Dubey, P. K.
J. Heterocycl. Chem. 2010, 47, in press. (b) Sawada, S.;
Okajima, S.; Aiyama, R.; Nokota, K.; Furuta, T.; Yokokura,
T.; Sugino, E.; Yamaguchi, K.; Miyasaka, T. Chem. Pharm.
Bull. 1991, 39, 1446. (c) Kingsbury, W. D.; Boehm, J. C.;
Jacas, D. R.; Holden, K. G.; Hecht, S. M.; Gallagher, G.;
Caranfa, M. J.; McCabe, F. L.; Faucette, L. F.; Johnson,
R. P.; Hertzberg, R. P. J. Med. Chem. 1991, 34, 98.
(d) Subrahmanyam, D.; Venkateswarlu, A.; Sarma, V. M.;
Sastry, T. V. R. S.; Krishna, C. V.; Madabhushi, S. US
6177439 B1, 2001. (e) Subrahmanyam, D.; Sarma, V. M.;
Venkateswarlu, A.; Sastry, T. V. R. S.; Srinivas, A. S. S. V.;
Krishna, C. V.; Deevi, D. S.; Kumar, S. A.; Babu, M. J.;
Damodaran, N. K. Bioorg. Med. Chem. Lett. 2000, 10, 369.
(f) Subrahmanyam, D.; Venkateswarlu, A.; Venkateswarao,
K.; Sastry, T. V. R. S.; Vandana, G.; Kumar, S. A. Bioorg.
Med. Chem. Lett. 1999, 9, 1633. (g) Kim, D.-K.; Lee, N.
Mini Rev. Med. Chem. 2002, 2, 611. (h) Hatefi, A.;
Amsden, B. Pharm. Res. 2002, 19, 1389.
(7) (a) Servais, A.; Azzouz, M.; Lopes, D.; Courillon, C.;
Malacria, M. Angew. Chem. Int. Ed. 2007, 46, 576.
(b) Beaume, A.; Courillon, C.; Derat, E.; Malacria, M.
Chem. Eur. J. 2008, 16, 1228.
(8) Twin, H.; Batey, R. Org. Lett. 2004, 6, 4913.
(9) (a) Nacro, K.; Zha, C. C.; Guzzo, P. R.; Herr, J.; Peace, D.;
Friedrich, T. D. Bioorg. Med. Chem. 2007, 13, 4237.
(b) Harayama, T.; Hori, A.; Serban, G.; Morikami, Y.;
Matsumoto, T.; Abe, H.; Takeuchi, Y. Tetrahedron 2004,
60, 10645. (c) Mason, J. J.; Bergman, J. Org. Biomol. Chem.
2007, 5, 2486. (d) Mhaske, S. B.; Argade, N. P. J. Org.
Chem. 2004, 69, 4563. (e) Chavan, S. P.; Sivappa, R.
Tetrahedron 2004, 60, 9931. (f) Mhaske, S. B.; Argade,
P. N. J. Org. Chem. 2004, 69, 4563.
(18) Luotonin B (2)
Yield 0.89 g (54%); mp 273–275 °C. IR (KBr): 1028, 1266,
1449, 2041, 2945, cm–1. 1H NMR (400 MHz, DMSO-d6):
d = 6.98 (d, J = 8.4 Hz, 1 H), 7.62–7.66 (m, 2 H), 7.78 (t,
J = 7.2 Hz, 1 H), 7.92–7.96 (m, 3 H), 8.23 (d, J = 8.0 Hz, 1
H), 8.28 (dd, J = 3.6 Hz, 8.4 Hz, 2 H), 8.80 (s, 1 H). 13
C
NMR (400 MHz, DMSO-d6): d = 80.5, 122.2, 126.1, 127.5,
128.2, 128.3, 128.7, 128.8, 129.6, 131.0, 132.8, 133.8,
134.7, 148.7, 149.1, 150.3, 151.5, 159.4. MS m/z (%) =
302.1 [M + 1], 246.2, 150.1. Anal Calcd for C18H11N3O2: C,
71.75; H, 3.68; N, 13.95. Found: C, 71.77; H, 3.69; N, 13.90.
(19) To a solution of luotonin B (0.35 g, 0.16 mol, 1 equiv) in
MeOH (3.5 mL, 10 V), Indion resin (0.1 g, 0.01 mmol, 0.1
equiv) was added, and the reaction mixture was heated at
55 °C for a period of 6–7 h. The reaction mixture was then
cooled, and the resin was filtered off and washed with
MeOH (1 mL). The filtrate was concentrated under reduced
pressure, and purified on a filter column using EtOAc–
hexane (30:70). The product was isolated as a white to off-
white solid in 80% (0.29 g) yield.
(10) Zhou, H.-B.; Liu, G.-S.; Yao, Z.-J. J. Org. Chem. 2007, 73,
6270.
(11) Sridharan, V.; Ribelles, P.; Ramos, T.; Menendez, J. C.
J. Org. Chem. 2009, 74, 5715.
(12) (a) Baruah, B.; Bhuyan, J. P. Tetrahedron 2009, 65, 7099.
(b) Baruah, B.; Deb, M. L.; Bhuyan, P. J. Synlett 2007, 1873.
(13) (a) Jana, G. P.; Ghorai, B. K. Tetrahedron 2007, 63, 12015.
(b) Chavan, S. P.; Pasupathy, K.; Sivappa, R.; Venkatraman,
M. S. Synth. Commun . 2004, 34, 3099. (c) Chavan, S. P.;
Sivappa, R. Tetrahedron Lett. 2004, 45, 3113.
(14) Takao, S.; Kazutoshi, O. J. Chem. Soc., Perkin Trans. 1
1999, 16, 2323.
(15) To a suspension of 2-cyanoquinoline-3-acetal (9, 1 g, 0.004
mol, 1 equiv) in AcOH (10 mL), methyl anthranilate (0.7 g,
0.005 mol, 1.05 equiv) was added, and the reaction mixture
was heated to reflux for a period of 12–14 h. The reaction
mass was then cooled, the precipitated product was filtered
Luotonin E
Yield 0.29 g (80%).; mp 222–224 °C. IR (KBr): 1047, 1237,
1300, 1375, 1730, 2985 cm–1. 1H NMR (400 MHz, CDCl3):
d = 3.60 (s, 3 H), 6.90 (s, 1 H), 7.58 (dt, J = 0.8, 7.6, 11.2 Hz,
1 H), 7.71 (t, J = 6.8 Hz, 1 H), 7.82–7.88 (m, 2 H), 7.99 (d,
J = 8.4 Hz, 1 H), 8.09 (d, J = 8.0 Hz, 1 H) 8.41 (dd, J = 1.2,
8.0 Hz, 1 H), 8.47 (d, J = 8.4 Hz, 1 H), 8.5 (s, 1 H). 13C NMR
(400 MHz, CDCl3): d = 56.3, 87.0, 122.2, 126.8, 127.8,
128.4, 128.6, 128.8, 130.0, 130.7, 131.3, 133.0, 134.8,
148.9, 150.4, 151.3, 160.7. MS: m/z (%) = 316.2 [M + 1],
Synlett 2011, No. 1, 84–88 © Thieme Stuttgart · New York