Synthesis and biological evaluation of highly functionalized analogues of ingenol

Journal of the American Chemical Society

Volumn 121, Issue 2, 1999, Pages 296-300

  Winkler, Jeffrey D ^a   Kim, Sanghee ^a   Harrison, Sean ^a   Lewin, Nancy E ^a   Blumberg, Peter M ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

INGENOL; NATURAL PRODUCT; PROTEIN KINASE C; RECEPTOR;

ARTICLE; CHEMICAL ANALYSIS; HYDROPHOBICITY; RECEPTOR BINDING; SYNTHESIS;

EID: 0033585571     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja9741842     Document Type: Article

References (29)

1. Baringa, M. Science 1997, 278, 1036.
2. For recent reviews, see: (a) Blackshear, P. J. J. Biol. Chem. 1993, 268, 1501. (b) Dekker, L. V.; Parker, P. J. Trends Biochem. Sci. 1994, 19, 73.
3. For recent reviews, see: (a) Blackshear, P. J. J. Biol. Chem. 1993, 268, 1501. (b) Dekker, L. V.; Parker, P. J. Trends Biochem. Sci. 1994, 19, 73.
4. (a) Hecker, E. In Carcinogenesis: A Comprehensive Survey, Mechanisms of Tumor Promotion and Cocarcinogenesis; Slaga, T. J., Sivak, A., Boutwell, R. K., Eds.; Raven: New York, 1987; Vol. 2, pp 11-48.
5. (b) Sugimura, T.; Fujiki, H. In Gann Monograph on Cancer Research; Makita, A., Tsuiki, S., Fujiki, H., Warren, L., Eds.; University of Tokyo Press: Tokyo, 1983; Vol. 29, pp 3-15.
6. (c) Mechanisms of Tumor Promotion; Slaga, T. J., Ed.; CRC: Boca Raton, FL, 1993-94; Vols. 1-4.
7. (d) Schmidt, R.; Aitken, A. In Naturally Occurring Phorbol Esters; Evans, F., Ed., CRC Press: Boca Raton, FL, 1986; pp 245-289.
8. (a) Jeffrey, A.; Liskamp, R. Proc. Natl. Acad. Sci. U.S.A. 1986, 83, 241.
9. (b) Wender, P.; Cribb, C.; Koehler, K.; Sharkey, M.; Herald, C.; Kamano, Y.; Pettit, G.; Blumberg, P. Proc. Natl. Acad. Sci. U.S.A. 1988, 85, 7197.
10. (c) Itai, A.; Kato, Y.; Tomioka, N.; Iitaka, Y.; Endo, Y.; Hasegawa, M.; Shudo, K.; Fujiki, H.; Sakai, S. Proc. Natl. Acad. Sci. U.S.A. 1988, 85, 3688.
11. (d) Cuthbertson, A.; Thomson, C. J. Mol. Graphics 1987, 192.
12. (e) Thomson, C.; Wilkie, J. Carcinogenesis 1989, 10, 531.
13. (f) Nakamura, H.; Kishi, Y.; Pajares, M.; Rando, R. Proc. Natl. Acad. Sci. U.S.A. 1989, 86, 9672.
14. Bradshaw, D.; Hill, C.; Nixon, J.; Wilkinson, S. Agents Actions 1993, 58, 135.
15. For recent reviews on the synthesis of ingenanes, see: (a) Kim, S.; Winkler, J. Chem. Soc. Rev. 1997, 26, 387. (b) Rigby, J. Stud. Nat. Prod. Chem. 1993, 12, 233.
16. For recent reviews on the synthesis of ingenanes, see: (a) Kim, S.; Winkler, J. Chem. Soc. Rev. 1997, 26, 387. (b) Rigby, J. Stud. Nat. Prod. Chem. 1993, 12, 233.
17. For synthetic studies since 1993, see: (a) Nakamura, T.; Matsui, T.; Tanino, K.; Kuwajima, I. J. Org. Chem. 1997, 62, 3032. (b) Rigby, J.; Claire, V.; Cuisiat, S.; Heeg, M. J. Org. Chem. 1996, 61, 7992. (c) Harmata, M.; Elahmad, S.; Barnes, C. Tetrahedron Lett. 1995, 36, 1397. (d) Winkler, J.; Hong, B.; Bahador, A.; Kazanietz, M.; Blumberg, P. J. Org. Chem. 1995, 60, 1381. (e) Winkler, J.; Hong, B.; Kim, S.; Lewin, N.; Blumberg, P. Synlett 1995, 533. (f) Winkler, J.; Henegar, K.; Hong, B.; Williard, P. J. Am. Chem. Soc. 1994, 116, 4183. (g) Rigby, J.; Cuisiat, S. J. Org. Chem. 1993, 58, 6286. (h) Funk, R.; Olmstead, T.; Parvez, M.; Stallman, J. J. Org. Chem. 1993, 58, 5873. (i) Winkler, J.; Gretler, E.; Williard, P. J. Org. Chem. 1993, 58, 1973. (j) Winkler, J.; Hong, B.; Bahador, A.; Kazanietz. M.; Blumberg, P. Bioorg. Med. Chem. Lett. 1993, 3, 577.
18. For synthetic studies since 1993, see: (a) Nakamura, T.; Matsui, T.; Tanino, K.; Kuwajima, I. J. Org. Chem. 1997, 62, 3032. (b) Rigby, J.; Claire, V.; Cuisiat, S.; Heeg, M. J. Org. Chem. 1996, 61, 7992. (c) Harmata, M.; Elahmad, S.; Barnes, C. Tetrahedron Lett. 1995, 36, 1397. (d) Winkler, J.; Hong, B.; Bahador, A.; Kazanietz, M.; Blumberg, P. J. Org. Chem. 1995, 60, 1381. (e) Winkler, J.; Hong, B.; Kim, S.; Lewin, N.; Blumberg, P. Synlett 1995, 533. (f) Winkler, J.; Henegar, K.; Hong, B.; Williard, P. J. Am. Chem. Soc. 1994, 116, 4183. (g) Rigby, J.; Cuisiat, S. J. Org. Chem. 1993, 58, 6286. (h) Funk, R.; Olmstead, T.; Parvez, M.; Stallman, J. J. Org. Chem. 1993, 58, 5873. (i) Winkler, J.; Gretler, E.; Williard, P. J. Org. Chem. 1993, 58, 1973. (j) Winkler, J.; Hong, B.; Bahador, A.; Kazanietz. M.; Blumberg, P. Bioorg. Med. Chem. Lett. 1993, 3, 577.
19. For synthetic studies since 1993, see: (a) Nakamura, T.; Matsui, T.; Tanino, K.; Kuwajima, I. J. Org. Chem. 1997, 62, 3032. (b) Rigby, J.; Claire, V.; Cuisiat, S.; Heeg, M. J. Org. Chem. 1996, 61, 7992. (c) Harmata, M.; Elahmad, S.; Barnes, C. Tetrahedron Lett. 1995, 36, 1397. (d) Winkler, J.; Hong, B.; Bahador, A.; Kazanietz, M.; Blumberg, P. J. Org. Chem. 1995, 60, 1381. (e) Winkler, J.; Hong, B.; Kim, S.; Lewin, N.; Blumberg, P. Synlett 1995, 533. (f) Winkler, J.; Henegar, K.; Hong, B.; Williard, P. J. Am. Chem. Soc. 1994, 116, 4183. (g) Rigby, J.; Cuisiat, S. J. Org. Chem. 1993, 58, 6286. (h) Funk, R.; Olmstead, T.; Parvez, M.; Stallman, J. J. Org. Chem. 1993, 58, 5873. (i) Winkler, J.; Gretler, E.; Williard, P. J. Org. Chem. 1993, 58, 1973. (j) Winkler, J.; Hong, B.; Bahador, A.; Kazanietz. M.; Blumberg, P. Bioorg. Med. Chem. Lett. 1993, 3, 577.
20. For synthetic studies since 1993, see: (a) Nakamura, T.; Matsui, T.; Tanino, K.; Kuwajima, I. J. Org. Chem. 1997, 62, 3032. (b) Rigby, J.; Claire, V.; Cuisiat, S.; Heeg, M. J. Org. Chem. 1996, 61, 7992. (c) Harmata, M.; Elahmad, S.; Barnes, C. Tetrahedron Lett. 1995, 36, 1397. (d) Winkler, J.; Hong, B.; Bahador, A.; Kazanietz, M.; Blumberg, P. J. Org. Chem. 1995, 60, 1381. (e) Winkler, J.; Hong, B.; Kim, S.; Lewin, N.; Blumberg, P. Synlett 1995, 533. (f) Winkler, J.; Henegar, K.; Hong, B.; Williard, P. J. Am. Chem. Soc. 1994, 116, 4183. (g) Rigby, J.; Cuisiat, S. J. Org. Chem. 1993, 58, 6286. (h) Funk, R.; Olmstead, T.; Parvez, M.; Stallman, J. J. Org. Chem. 1993, 58, 5873. (i) Winkler, J.; Gretler, E.; Williard, P. J. Org. Chem. 1993, 58, 1973. (j) Winkler, J.; Hong, B.; Bahador, A.; Kazanietz. M.; Blumberg, P. Bioorg. Med. Chem. Lett. 1993, 3, 577.
21. For synthetic studies since 1993, see: (a) Nakamura, T.; Matsui, T.; Tanino, K.; Kuwajima, I. J. Org. Chem. 1997, 62, 3032. (b) Rigby, J.; Claire, V.; Cuisiat, S.; Heeg, M. J. Org. Chem. 1996, 61, 7992. (c) Harmata, M.; Elahmad, S.; Barnes, C. Tetrahedron Lett. 1995, 36, 1397. (d) Winkler, J.; Hong, B.; Bahador, A.; Kazanietz, M.; Blumberg, P. J. Org. Chem. 1995, 60, 1381. (e) Winkler, J.; Hong, B.; Kim, S.; Lewin, N.; Blumberg, P. Synlett 1995, 533. (f) Winkler, J.; Henegar, K.; Hong, B.; Williard, P. J. Am. Chem. Soc. 1994, 116, 4183. (g) Rigby, J.; Cuisiat, S. J. Org. Chem. 1993, 58, 6286. (h) Funk, R.; Olmstead, T.; Parvez, M.; Stallman, J. J. Org. Chem. 1993, 58, 5873. (i) Winkler, J.; Gretler, E.; Williard, P. J. Org. Chem. 1993, 58, 1973. (j) Winkler, J.; Hong, B.; Bahador, A.; Kazanietz. M.; Blumberg, P. Bioorg. Med. Chem. Lett. 1993, 3, 577.
22. For synthetic studies since 1993, see: (a) Nakamura, T.; Matsui, T.; Tanino, K.; Kuwajima, I. J. Org. Chem. 1997, 62, 3032. (b) Rigby, J.; Claire, V.; Cuisiat, S.; Heeg, M. J. Org. Chem. 1996, 61, 7992. (c) Harmata, M.; Elahmad, S.; Barnes, C. Tetrahedron Lett. 1995, 36, 1397. (d) Winkler, J.; Hong, B.; Bahador, A.; Kazanietz, M.; Blumberg, P. J. Org. Chem. 1995, 60, 1381. (e) Winkler, J.; Hong, B.; Kim, S.; Lewin, N.; Blumberg, P. Synlett 1995, 533. (f) Winkler, J.; Henegar, K.; Hong, B.; Williard, P. J. Am. Chem. Soc. 1994, 116, 4183. (g) Rigby, J.; Cuisiat, S. J. Org. Chem. 1993, 58, 6286. (h) Funk, R.; Olmstead, T.; Parvez, M.; Stallman, J. J. Org. Chem. 1993, 58, 5873. (i) Winkler, J.; Gretler, E.; Williard, P. J. Org. Chem. 1993, 58, 1973. (j) Winkler, J.; Hong, B.; Bahador, A.; Kazanietz. M.; Blumberg, P. Bioorg. Med. Chem. Lett. 1993, 3, 577.
23. For synthetic studies since 1993, see: (a) Nakamura, T.; Matsui, T.; Tanino, K.; Kuwajima, I. J. Org. Chem. 1997, 62, 3032. (b) Rigby, J.; Claire, V.; Cuisiat, S.; Heeg, M. J. Org. Chem. 1996, 61, 7992. (c) Harmata, M.; Elahmad, S.; Barnes, C. Tetrahedron Lett. 1995, 36, 1397. (d) Winkler, J.; Hong, B.; Bahador, A.; Kazanietz, M.; Blumberg, P. J. Org. Chem. 1995, 60, 1381. (e) Winkler, J.; Hong, B.; Kim, S.; Lewin, N.; Blumberg, P. Synlett 1995, 533. (f) Winkler, J.; Henegar, K.; Hong, B.; Williard, P. J. Am. Chem. Soc. 1994, 116, 4183. (g) Rigby, J.; Cuisiat, S. J. Org. Chem. 1993, 58, 6286. (h) Funk, R.; Olmstead, T.; Parvez, M.; Stallman, J. J. Org. Chem. 1993, 58, 5873. (i) Winkler, J.; Gretler, E.; Williard, P. J. Org. Chem. 1993, 58, 1973. (j) Winkler, J.; Hong, B.; Bahador, A.; Kazanietz. M.; Blumberg, P. Bioorg. Med. Chem. Lett. 1993, 3, 577.
24. For synthetic studies since 1993, see: (a) Nakamura, T.; Matsui, T.; Tanino, K.; Kuwajima, I. J. Org. Chem. 1997, 62, 3032. (b) Rigby, J.; Claire, V.; Cuisiat, S.; Heeg, M. J. Org. Chem. 1996, 61, 7992. (c) Harmata, M.; Elahmad, S.; Barnes, C. Tetrahedron Lett. 1995, 36, 1397. (d) Winkler, J.; Hong, B.; Bahador, A.; Kazanietz, M.; Blumberg, P. J. Org. Chem. 1995, 60, 1381. (e) Winkler, J.; Hong, B.; Kim, S.; Lewin, N.; Blumberg, P. Synlett 1995, 533. (f) Winkler, J.; Henegar, K.; Hong, B.; Williard, P. J. Am. Chem. Soc. 1994, 116, 4183. (g) Rigby, J.; Cuisiat, S. J. Org. Chem. 1993, 58, 6286. (h) Funk, R.; Olmstead, T.; Parvez, M.; Stallman, J. J. Org. Chem. 1993, 58, 5873. (i) Winkler, J.; Gretler, E.; Williard, P. J. Org. Chem. 1993, 58, 1973. (j) Winkler, J.; Hong, B.; Bahador, A.; Kazanietz. M.; Blumberg, P. Bioorg. Med. Chem. Lett. 1993, 3, 577.
25. For synthetic studies since 1993, see: (a) Nakamura, T.; Matsui, T.; Tanino, K.; Kuwajima, I. J. Org. Chem. 1997, 62, 3032. (b) Rigby, J.; Claire, V.; Cuisiat, S.; Heeg, M. J. Org. Chem. 1996, 61, 7992. (c) Harmata, M.; Elahmad, S.; Barnes, C. Tetrahedron Lett. 1995, 36, 1397. (d) Winkler, J.; Hong, B.; Bahador, A.; Kazanietz, M.; Blumberg, P. J. Org. Chem. 1995, 60, 1381. (e) Winkler, J.; Hong, B.; Kim, S.; Lewin, N.; Blumberg, P. Synlett 1995, 533. (f) Winkler, J.; Henegar, K.; Hong, B.; Williard, P. J. Am. Chem. Soc. 1994, 116, 4183. (g) Rigby, J.; Cuisiat, S. J. Org. Chem. 1993, 58, 6286. (h) Funk, R.; Olmstead, T.; Parvez, M.; Stallman, J. J. Org. Chem. 1993, 58, 5873. (i) Winkler, J.; Gretler, E.; Williard, P. J. Org. Chem. 1993, 58, 1973. (j) Winkler, J.; Hong, B.; Bahador, A.; Kazanietz. M.; Blumberg, P. Bioorg. Med. Chem. Lett. 1993, 3, 577.
26. For synthetic studies since 1993, see: (a) Nakamura, T.; Matsui, T.; Tanino, K.; Kuwajima, I. J. Org. Chem. 1997, 62, 3032. (b) Rigby, J.; Claire, V.; Cuisiat, S.; Heeg, M. J. Org. Chem. 1996, 61, 7992. (c) Harmata, M.; Elahmad, S.; Barnes, C. Tetrahedron Lett. 1995, 36, 1397. (d) Winkler, J.; Hong, B.; Bahador, A.; Kazanietz, M.; Blumberg, P. J. Org. Chem. 1995, 60, 1381. (e) Winkler, J.; Hong, B.; Kim, S.; Lewin, N.; Blumberg, P. Synlett 1995, 533. (f) Winkler, J.; Henegar, K.; Hong, B.; Williard, P. J. Am. Chem. Soc. 1994, 116, 4183. (g) Rigby, J.; Cuisiat, S. J. Org. Chem. 1993, 58, 6286. (h) Funk, R.; Olmstead, T.; Parvez, M.; Stallman, J. J. Org. Chem. 1993, 58, 5873. (i) Winkler, J.; Gretler, E.; Williard, P. J. Org. Chem. 1993, 58, 1973. (j) Winkler, J.; Hong, B.; Bahador, A.; Kazanietz. M.; Blumberg, P. Bioorg. Med. Chem. Lett. 1993, 3, 577.
27. For a discussion of the role of the corresponding methyl group in the phorbol esters, see: Sugita, K.; Neville, C.; Sodeoka, M.; Sasai, H.; Shibasaki, M. Tetrahedron Lett. 1995, 1067.
28. For a recent discussion of the possible role of the ingenol cyclopropane, see: Krauter, G.; Von Der Lieth, C.; Schmidt, R.; Hecker, E. Eur. J. Biochem, 1996, 242, 417. For a discussion of the role of the cyclopropane ring of phorbol in the crystal structure of the PKC activator-binding domain in complex with phorbol 13-acetate, see: Zhang, G.; Kazanietz, M. G.; Blumberg, P. M.; Hurley, J. H. Cell 1995, 81, 917-924.
29. For a recent discussion of the possible role of the ingenol cyclopropane, see: Krauter, G.; Von Der Lieth, C.; Schmidt, R.; Hecker, E. Eur. J. Biochem, 1996, 242, 417. For a discussion of the role of the cyclopropane ring of phorbol in the crystal structure of the PKC activator-binding domain in complex with phorbol 13-acetate, see: Zhang, G.; Kazanietz, M. G.; Blumberg, P. M.; Hurley, J. H. Cell 1995, 81, 917-924.