The first chemical synthesis of wortmannin by starting from hydrocortisone

Tetrahedron Letters

Volumn 37, Issue 34, 1996, Pages 6141-6144

  Sato, Seiji ^a   Nakada, Masahisa ^a   Shibasaki, Masakatsu ^a  

^a UNIVERSITY OF TOKYO   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ENZYME INHIBITOR; HYDROCORTISONE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; UNCLASSIFIED DRUG; WORTMANNIN;

ARTICLE; DRUG SYNTHESIS; REACTION ANALYSIS;

EID: 0030593589     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)01332-9     Document Type: Article

References (30)

1. 1. a) Brian, P. W.; Curtis, P. J.; Hemming, H. G.; Norris, G. L. F. Trans. Brit. Mycol. Soc., 1957, 40, 366.
2. b) Petcher, T. J.; Weber, H. -P.; Kis, Z. J. Chem. Soc., Chem. Commun. 1972, 1061-1062.
3. c) MacMillan, J.; Simpson, T. J.; Yeboah, S. K. J. Chem. Soc., Chem. Commun. 1972, 1063.
4. d) MacMillan, J.; Vanstone, A. E.; Yeboah, S. K. J. Chem. Soc., Perkin Trans. 1 1972, 2898-2903.
5. 2. a) Dodge, J. A.; Bryant, H. U.; Kim, J.; Matter, W. F.; Norman, B. H.; Srinivasan, U.; Vlahos, C. J.; Sato, M. Bioorg. Med. Chem. Lett. 1995, 5, 1713-1718
6. b) Nakanishi, S.; Kakita, S.; Takahashi, I.; Kawahara, K.; Tsukuda, E.; Sano, T.; Yamada, K.; Yoshida, M.; Kase, H.; Matsuda, Y. J. Biol. Chem. 1992, 267, 2157-2163.
7. c) Wiesinger, D.; Gubler, H. U.; Haefliger, W.; Hauser, D. Experientia 1974, 135-136.
8. 3. a) Kanai, F.; Ito, K.; Todaka, M.; Hayashi, H.; Kamohara, S.; Ishii, K.; Okada, T.; Hazeki, O.; Ui, M.; Ebina, Y. Biochem. Biophys. Res. Commun. 1993, 195, 762-768.
9. b) Yano, H.; Nakanishi, S.; Kimura, K.; Hanai, N.; Saitoh, Y.; Fukui, Y.; Nonomura, Y.; Matsuda, Y. J. Biol. Chem. 1993, 268, 25846-25856.
10. c) Arcaro, A.; Wymann, M. P. Biochem. J. 1993, 296, 297-301.
11. d) Okada, T.; Sakuma, L.; Fukui, Y.; Hazeki, O.; Ui, M. J. Biol. Chem. 1994, 269, 3563-3567. For review, see,
12. a) Stephens, L. Biochem. Soc. Trans. 1995, 23, 207-221.
13. b) Vlahos, C. J. Drugs of the Future 1995, 20, 165-171.
14. c) Stephens, L. R.; Jackson, T. R.; Hawkins, P. T. Biochim. Biophys. Acta 1993, 1179, 27-75.
15. d) Parker, P. J.; Waterfield, M. D. Cell Growth Diff. 1992, 3, 747-752.
16. 4. Honzawa, S.; Nakada, M.; Kurosu, H.; Hazeki, O.; Katada, T.; Shibasaki, M. Chem. Pharm. Bull. 1995, 43, 2276-2278.
17. b) Kurosu, H.; Hazeki, O.; Kukimoto, I.; Honzawa, S.; Shibasaki, M.; Nakada, M.; Ui, M.; Katada, T. Biochem. Biophys. Res. Commun. 1995, 216, 655-661.
18. 5. Zhao, Q.; Li, Z. Steroids 1994, 59, 190 -195.
19. 6. ApSimon, J. W.; King, R. R.; Rosenfeld, J. J. Can. J. Chem. 1969, 47, 1989-1998.
20. 7. The results of the NOE experiments are as follow. (equation presented)
21. 8. Many attempts to invert its configuration without opening an epoxide functionality were unsuccessful.
22. 9. The results of the NOE experiments are as follow. (equation presented)
23. 10. Evans, D. A.; Chapman, K. T.; Carreira, E. M. J. Am. Chem. Soc. 1988, 110, 3560-3578.
24. 11. The allylic alcohol 27 was readily formed by treatment of 16 with base. However, conversion of 27 to 25 was unsuccessful. (equation presented)
25. 4 and pyridine.
26. 13. The stereochemistries of 17 and 18 were determined by NOE experiments. (equation presented)
27. 14. Conversion of 18 to wortmannin (25) was unsuccessful owing to the difficulty in forming a furan ring.
28. 15. For a synthetic approach to 25, see: Broka, C. A.; Ruhland, B. J. Org. Chem. 1992, 57, 4888-4894.
29. 16. Many direct transformations of 20 to 22 were unsuccessful.
30. 17. Haefliger, W.; Kis, Z.; Hauser, D. Helv. Chim. Acta 1975, 58, 1620-1628.