Utilization of the benzo[c]phenanthridinones 16 in the total
syntheses of natural alkaloids has been demonstrated as shown
in Scheme 5. Oxidation of amides 16 with DDQ in either
benzene or 1,4-dioxane failed in giving the desired dehydrogenated
products. However, the N-methylated products 17 could be readily
aromatized by oxidation of DDQ. Thus, treatment of dihydro
benzo[c]phenanthridinones 16 with iodomethane and potassium
hydroxide in acetone afforded the corresponding N-methylated
products 17 in quantitative yields. Oxidation of 17 with DDQ was
successfully carried out, giving oxybenzo[c]phenanthridine alka-
loids in good yields. Reduction9 of oxybenzo[c]phenanthridines
with LiAlH4 followed by treatment with HCl gave the de-
sired quaternary benzo[c]phenanthridine chlorides in high yields
(Scheme 5).
Notes and references
1 V. Simanek, in The Alkaloids, ed. A. Brossi, Academic Press, New York,
1985, Vol. 26, pp. 185–229.
2 (a) C. Vavrecˇkova´, I. Gawlik and K. Mu¨ller, Planta Med., 1996, 62,
397; (b) T. Schemeller, B. Latz-Bruning and M. Wink, Phytochemistry,
1997, 44, 257; (c) F.-C. Huang and T. M. Kutchan, Phytochemistry,
2000, 53, 555.
3 (a) Z. Taira, M. Matsumoto, S. Ishida, T. Ichikawa and Y. Sakiya,
Chem. Pharm. Bull., 1994, 42, 1556; (b) J. M. Herbert, J. M. Augereau,
J. Gleye and J. P. Maffrand, Biochem. Biophys. Res. Commun., 1990,
172, 993; (c) S.-D. Fang, L.-K. Wang and S. M. Hecht, J. Org. Chem.,
1993, 58, 5025; (d) T. Nakanishi and M. Suzuki, J. Nat. Prod., 1998,
61, 1263.
4 (a) H. Ishii, Y.-I. Ichikawa, E. Kawanabe, M. Ishikawa, T. Ishikawa,
K. Kuretani, M. Inomata and A. Hoshi, Chem. Pharm. Bull., 1985, 33,
4139; (b) T. Harayama, Heterocycles, 2005, 65, 697; (c) T. Harayama,
T. Sato, Y. Nakano, H. Abe and Y. Takeuchi, Heterocycles, 2003,
59, 293; (d) R. P. Korivi and C.-H Cheng, Chem.–Eur. J., 2010, 16,
282.
5 (a) B. Clement, M. Weide, U. Wolschendorf and I. Kock, Angew. Chem.,
Int. Ed., 2005, 44, 635; (b) I. Kock and B. Clement, Synthesis, 2005,
1052.
6 J.-P. Duan and C.-H. Cheng, Tetrahedron Lett., 1993, 34, 4019.
7 D. K. Rayabarapu, P. Shukla and C.-H. Cheng, Org. Lett., 2003, 5,
4903.
8 S. Madan and C.-H. Cheng, J. Org. Chem., 2006, 71, 8312.
9 (a) M. Hanaoka, T. Motonishi and C. Mukai, J. Chem. Soc., Perkin
Trans. 1, 1986, 2253; (b) T. Harayama, T. Akiyama, H. Akamastsu, K.
Kawano, H. Abe and Y. Takeuchi, Synthesis, 2001, 444.
10 H. A. McManus, M. J. Fleming and M. Lautens, Angew. Chem., Int.
Ed., 2007, 46, 433.
11 (a) J.-P. Duan and C.-H. Cheng, Organometallics, 1995, 14, 1608; (b)
C.-C. Feng, M. Nandi, T. Sambaiah and C.-H. Cheng, J. Org. Chem.,
1999, 64, 3538; (c) D. K. Rayabarapu and C.-H. Cheng, Acc. Chem.
Res., 2007, 40, 971.
12 R. J. Mattson, C. P. Sloan, C. C. Lockhart, J. D. Catt, Q. Gao and S.
Huang, J. Org. Chem., 1999, 64, 8004.
Scheme 5 Syntheses of some benzo[c]phenanthridine alkaloids.
13 D. E. Bogucki and J. L. Charlton, J. Org. Chem., 1995, 60, 588.
14 B. A. Hathaway, K. L. White and M. E. McGill, Synth. Commun., 2007,
37, 3855.
15 Z.-Q. Cong, C.-L. Wang, T. Chen and B.-Z. Yin, Synth. Commun.,
2006, 36, 679.
16 (a) F. S. Gibson, S. C. Bergmeier and H. Rapoport, J. Org. Chem.,
1994, 59, 3216; (b) D. S. Bose and V. Lakshminarayana, Synthesis,
1999, 66; (c) T. Tsuji, T. Kataoka, M. Yoshioka, Y. Sendo, Y. Nishitani,
S. Hirai, T. Maeda and W. Nagata, Tetrahedron Lett., 1979, 20, 2793;
(d) R. S. Lott, V. S. Chauhan and C. H. Stammer, J. Chem. Soc., Chem.
Commun., 1979, 11, 495.
In conclusion, a concise and versatile strategy for the total syn-
thesis of benzo[c]phenanthridine alkaloids using readily available
starting materials and inexpensive reagents has been developed.
It features a palladium-catalyzed tandem ring-opening coupling–
cyclization process as a key synthetic step. This efficient strategy
should allow easy access to a variety of benzo[c]phenanthridine
alkaloids and their analogues.
Financial support from National Key Technology R&D Pro-
gram (grant No2011BAE06B05) is gratefully acknowledged.
17 H. Nagaoka, G. Schmid, H. Iio and Y. Kishi, Tetrahedron Lett., 1981,
22, 899.
This journal is
The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 3133–3135 | 3135
©