Novel syntheses of camptothecin alkaloids. Part I. Intramolecular [4 + 2] cycloadditions of N-arylimidates and 4H-3,1-benzoxazin-4-ones as 2-aza-1,3-dienes

Tetrahedron Letters

Volumn 37, Issue 32, 1996, Pages 5679-5682

  Fortunak, Joseph M D ^a   Mastrocola, Antonietta R ^a   Mellinger, Mark ^a   Sisti, Nicolas J ^a   Wood, Jeffery L ^a   Zhuang, Zhi Ping ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

CAMPTOTHECIN DERIVATIVE; PYRROLO[3,4 B]QUINOLINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG SYNTHESIS; REACTION ANALYSIS;

EID: 0030570906     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)01204-X     Document Type: Article

References (34)

1. 1. Wall, M.E.; Wani, M.C.; Cook, C.E.; Palmer, K.H.; McPhail, A.T.; Sim, G.A. J.Am. Chem. Soc. 1966, 88, 3888.
2. 2. Hsiang, Y.-H.; Hertzberg, R.; Hecht, S.; Liu, L.F. J. Biol. Chem. 1985, 260, 14873.
3. 3. Giovanella, B.C.; Stehlin, J.S.; Wall, M.E.; Wani, M.C.; Nicholas, A.W.; Liu, L.F.; Silber, R. Potmesil, M. Science 1989, 246, 1046.
4. 4. a) Kingsbury, W.D.; et. al. J. Med. Chem. 1991, 34, 98.
5. b) Sawada, S.; et al. Chem. Pharm. Bull. 1991, 39, 1446.
6. c) Miyasaka, T.; Sawada, S.; Nokata, K.; Mutai, M. U.S. Patent 4 545 880, 1985.
7. d) Luzzio, M.J.; et. al. Proc. Am Assoc. Cancer Res. 1993, 34, 332..
8. 5. Irinotecan (2) is a marketed anticancer agent in Japan and is currently in Clinical development in the United States sponsored by the Upjohn/Pharmacia Corp.
9. 6. a) Wani, M.C.; et. al. J. Med. Chem. 1980, 23, 554.
10. b) Eckert, H. Angew. Chem. Int'l. Ed. Engl. 1981, 20, 208.
11. c) Pan, P.C.; et. al. Acta Chim. Sinica 1975, 33, 71.
12. d) Cia, J.C.; Hutchinson, C.R. Chem. Heterocycl. Compd. 1983, 25, 753.
13. e) Cia, J.C.; Hutchinson, C.R. The Alkaloids: Chemistry and Pharmacology, Brossi, A., Ed.; Academic Press: New York, 1983; Vol. 21, p. 101.
14. f) Shen, W.; Coburn, C.A.; Bornmann, W.G.; Danishefsky, S.J. J. Org. Chem. 1993, 58, 611.
15. g) Curran, D.P.; Bo, S.-B.; Josien, H. Angew. Chem. Int'l. Ed. Engl. 1995, 54, 2683; Curran, D.P.; Liu, H. J. Am. Chem. Soc., 1992, 114, 5863; Curran, D.P.; Ko, S.-B. J. Org. Chem., 1994, 59, 6139.
16. g) Curran, D.P.; Bo, S.-B.; Josien, H. Angew. Chem. Int'l. Ed. Engl. 1995, 54, 2683; Curran, D.P.; Liu, H. J. Am. Chem. Soc., 1992, 114, 5863; Curran, D.P.; Ko, S.-B. J. Org. Chem., 1994, 59, 6139.
17. g) Curran, D.P.; Bo, S.-B.; Josien, H. Angew. Chem. Int'l. Ed. Engl. 1995, 54, 2683; Curran, D.P.; Liu, H. J. Am. Chem. Soc., 1992, 114, 5863; Curran, D.P.; Ko, S.-B. J. Org. Chem., 1994, 59, 6139.
18. h) Jew, S.-s.; Ok, K.-d.; Kim, H.-j.; Kim, M.G.; Kim, J.M.; Hah, J.M.; Cho, Y.-s. Tetrahedron: Asymmetry 1995, 6, 1245.
19. i) Fang, F.G.; Xie, S.; Lowery, M.W. J. Org. Chem., 1994, 59, 6142.
20. 7. a) Comins, D.L.; Hong, H.; Jianhua, G. Tetrahedron Lett. 1994, 35 5331.
21. b) Comins, D.L.; Hong, H.; Saha, J.K.; Jianhua, G. J. Org. Chem. 1994, 59, 5120.
22. c) Comins, D.L.; Saha, J.K. Tetrahedron Lett. 1995, 36, 7995.
23. d) Comins, D.L.; Baevsky, M.F.; Hong, H. J. Am. Chem. Soc. 1992, 114, 10971.
24. 13C NMR, exact mass determination and/or elemental analysis. Yields are given after purification.
25. 9. Barluenga, J.; et. al. Synlett. 1990, 129.
26. 10. Grieco, P.A.; Bahsas, A.; Tetrahedron Lett. 1988, 29, 5855.
27. 11. Mellor, J.M.; Merriman, G.D.; Mitchell, P.L.; Tetrahedron 1995, 51, 12383.
28. 12. For a review of applicable references see Boger, D.L.; Weinreb, S.M. Hetero Diels-Alder Methodology in Organic Synthesis, Wasserman, H., Ed.; Academic Press: San Diego, 1987; Vol. 47, pp. 255-260, 278-299.
29. 13. Since formation of the imidate produces one mole equivalent of fluoroboric acid this reaction is likely an inverse electron-demand [4+2] cycloaddition of the protonated azadiene with the "electron-rich" alkyne. The reaction occurs, although more slowly, through the neutral imidate. Photolysis, radical traps or initiators have no significant effect on the reaction. The benzoxazinones react uniformly in a [4+2] fashion whereas the p-nitro-N-arylimidate reacts as below, giving the desired cycloaddition in poor yield (15-20%; compare with ref. 10). Lewis acid catalyzed reaction of various imidates or reaction through the O-silyl-imidates also gives primarily the reaction pathway indicated below. (formula presented)
30. 14. Heller, G.; Fiesselman, G. Justus Liebig's Ann. Chem. 1902, 324, 134.
31. 15. Fenton, G.; Newton, G.G.; et. al. J. Med. Chem. 1989, 32, 265.
32. 16. a) Hofle, G.; Hollitzer, O.; Steglich, W. Angew. Chem. Int'l. Ed. Engl. 1972, 11, 720.
33. b) Steglich, W.; Hollitzer, O. Angew. Chem. Int'l. Ed. Engl. 1973, 12, 495.
34. 17. A preliminary, partial disclosure of this work was first presented at the University of New Orleans, February 21, 1992.