Total synthesis of (+)-RK-286c, (+)-MLR-52, (+)-staurosporine, and (+)-K252a

Journal of the American Chemical Society

Volumn 118, Issue 43, 1996, Pages 10656-10657

  Wood, John L ^a   Stoltz, Brian M ^a   Goodman, Steven N ^a  

^a YALE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4' DEMETHYLAMINO 4' HYDROXYSTAUROSPORINE; K 252A; STAUROSPORINE; UNCLASSIFIED DRUG;

ARTICLE; CHIRALITY; DRUG SYNTHESIS; ENANTIOMER; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0029841520     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja9626143     Document Type: Article

References (24)

1. For reviews on the synthesis and biological activity of indolocarbazoles, see: (a) Bergman, J. Stud. Nat. Prod. Chem., Part A 1988, 1, 3. (b) Gribble, G. W.; Berthel, S. J. Stud. Nat. Prod. Chem. 1993, 12, 365. (c) Steglich, W. Fortschr. Chem. Org. Naturst. 1987, 51, 216. (d) Omura, S.; Sasaki, Y.; Iwai, Y.; Takeshima, H. J. Antibiot. 1995, 48, 535.
2. For reviews on the synthesis and biological activity of indolocarbazoles, see: (a) Bergman, J. Stud. Nat. Prod. Chem., Part A 1988, 1, 3. (b) Gribble, G. W.; Berthel, S. J. Stud. Nat. Prod. Chem. 1993, 12, 365. (c) Steglich, W. Fortschr. Chem. Org. Naturst. 1987, 51, 216. (d) Omura, S.; Sasaki, Y.; Iwai, Y.; Takeshima, H. J. Antibiot. 1995, 48, 535.
3. For reviews on the synthesis and biological activity of indolocarbazoles, see: (a) Bergman, J. Stud. Nat. Prod. Chem., Part A 1988, 1, 3. (b) Gribble, G. W.; Berthel, S. J. Stud. Nat. Prod. Chem. 1993, 12, 365. (c) Steglich, W. Fortschr. Chem. Org. Naturst. 1987, 51, 216. (d) Omura, S.; Sasaki, Y.; Iwai, Y.; Takeshima, H. J. Antibiot. 1995, 48, 535.
4. For reviews on the synthesis and biological activity of indolocarbazoles, see: (a) Bergman, J. Stud. Nat. Prod. Chem., Part A 1988, 1, 3. (b) Gribble, G. W.; Berthel, S. J. Stud. Nat. Prod. Chem. 1993, 12, 365. (c) Steglich, W. Fortschr. Chem. Org. Naturst. 1987, 51, 216. (d) Omura, S.; Sasaki, Y.; Iwai, Y.; Takeshima, H. J. Antibiot. 1995, 48, 535.
5. For the enantioselective total synthesis of (+)- and (-)-K252a, see: Wood, J. L.; Stoltz, B. M.; Dietrich, H.-J. J. Am. Chem. Soc. 1995, 117, 10413.
6. For the isolation of (+)-K252a, see: Kase, H.; Iwahashi, K; Matsuda, Y. J. Antibiot. 1986, 39, 1059.
7. For an excellent full account of the landmark Danishefsky-Link synthesis of staurosporine, see: Link, J. T.; Raghavan, S.; Gallant, M.; Danishefsky, S. J.; Chou, T. C.; Ballas, L. M. J. Am. Chem. Soc. 1996, 118, 2825.
8. For the isolation of (+)-staurosporine, see: Omura, S.; Iwai, Y.; Hirano, A.; Nakagawa, A.; Awaya, J.; Tsuchiya, H.; Takahashi, Y.; Masuma, R. J. Antibiot. 1977, 30, 275.
9. Takahashi, H.; Osada, H.; Uramoto, M.; Isono, K. J. Antibiot. 1990, 43, 168.
10. McAlpine, J. B.; Karwowski, J. P.; Jackson, M.; Mullally, M. M.; Hochlowski, J. E.; Premachandran, U.; Burres, N. S. J. Antibiot. 1994, 47, 281.
11. Our initial model system work in developing this approach has been disclosed in part, see: (a) Stoltz, B. M.; Wood, J. L. Tetrahedron Lett. 1995, 36, 8543. (b) Stoltz, B. M.; Wood, J. L. Tetrahedron Lett. 1996, 37, 3929.
12. Our initial model system work in developing this approach has been disclosed in part, see: (a) Stoltz, B. M.; Wood, J. L. Tetrahedron Lett. 1995, 36, 8543. (b) Stoltz, B. M.; Wood, J. L. Tetrahedron Lett. 1996, 37, 3929.
13. 3).
14. Pfitzner, K. E.; Moffatt, J. G. J. Am. Chem. Soc. 1965, 87, 5670.
15. 8b
16. 2
17. 4
18. Arhart, R. J.; Martin, J. C. J. Am. Chem. Soc. 1972, 94, 5003.
19. This approach was adopted following failed attempts to oxidize (+)-11 to the elusive 9.
20. Tanida, S.; Takizawa, M.; Takahashi, T.; Tsubotani, S.; Harada, S. J. Antibiot. 1989, 42, 1619.
21. Krishnamurthy, S. Tetrahedron Lett. 1982, 23, 3315.
22. Spectroscopic data for our synthetic staurosporine were identical to a sample kindly provided by Professor Danishefsky.
23. The indicated number of steps refer to the total number of transformations required to convert o-toluidine, glycine ethyl ester, and methyl-2-diazo-3-oxobutyrate to the specified product.
24. 7 and the recent report that Streptomyces longisporoflavus R-19 produces both staurosporine and K252a, see: Fredenhagen, A.; Peter, H. H. Tetrahedron 1996, 52, 1235.