Application of the Pictet-Spengler reaction in combinatorial chemistry

Tetrahedron Letters

Volumn 37, Issue 32, 1996, Pages 5633-5636

  Mayer, John P ^a   Bankaitis Davis, Danute ^a   Zhang, Jingwen ^a   Beaton, Graham ^a   Bjergarde, Kirsten ^a   Andersen, Catherine M ^a   Goodman, Burton A ^a   Herrera, Charles J ^a  

^a AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

TRYPTOLINE DERIVATIVE;

ARTICLE; DRUG SYNTHESIS; REACTION ANALYSIS;

EID: 0030570866     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)01219-1     Document Type: Article

References (26)

1. 1) a) Furka, A.; Sebestyen, F.; Asgedom, M.; Dibo, G. Int. J. Pept. Prot. Res. 1991, 37, 487.
2. b) Houghten, R. A.; Pinilla, C.; Blondelle, S. E.; Appel, J.R.; Dooley, C. T.; Cuervo, J. H. Nature. 1991, 354, 84.
3. c) Owens, R. A.; Gesellchen, P. D.; Houchins, B. J.; DiMarchi, R. D. Biochem. Biophys. Res. Comm., 1991, 181, 402.
4. d) Lam, K. S.; Salmon, S. E.; Hersh, E. M.; Hruby, V. J.; Kazmierski, W. M.; Knapp, R. J. Nature 1991, 354, 82.
5. e) For a discussion of recent developments in this field see: Chem. Eng. News 1996, 74, 28.
6. 2) Merrifield, R. B. J. Am. Chem. Soc. 1963, 85, 2149.
7. 3) a) Bunin, B. A.; Ellman, J. A. J. Am. Chem. Soc. 1992, 114, 10997.
8. b) DeWitt, S. H.; Kiely, J. S.; Stankovic, C. J.; Schroeder, M. C.; Reynolds Cody, D. M.; Pavia, M. R. Proc. Natl. Acad. Sci. USA 1993, 90, 6909.
9. c) Moon, H.; Schore, N. E.; Kurth, M. J. J. Org. Chem . 1992, 57, 6088.
10. d) Beebe, X.; Schore, N. E.; Kurth, M. J. J. Am. Chem. Soc. 1992, 114, 10061.
11. e) Patek, M.; Drake, B.; Lebl, M. Tetrahedron Lett. 1995, 36, 2227.
12. f) Murphy, M. M.; Schullek, J. R.; Gordon, E. M.; Gallop, M. A. J. Am. Chem. Soc. 1995, 117, 7029.
13. 4) The Alkaloids, Chemistry and Physiology; Manske, R. H. F. Ed.; Academic Press: New York, 1981; vol XX.
14. 5) a) Braestrup, C.; Nielsen, M.; Olsen, C. E. Proc. Natl. Acad. Sci. USA. 1980, 77, 2228. Braestrup, C. Neurochem., 1981, 37, 333.
15. 5) a) Braestrup, C.; Nielsen, M.; Olsen, C. E. Proc. Natl. Acad. Sci. USA. 1980, 77, 2228. Braestrup, C. Neurochem., 1981, 37, 333.
16. b) Abou-Gharbia, M.; Patel, R. U.; Moyer, J. A.; Muth, T. A. J. Med. Chem. 1987, 30, 1100.
17. c) Abou-Gharbia, M.; Patel, R. U.; Webb, M. B.; Moyer, J. A.; Andree, T. H.; Muth, T. A. J. Med. Chem. 1987, 30, 1818.
18. 6) During completion of this work a similar approach to β-carbolines utilizing the Pictet-Spengler reaction was reported: Kaljuste, K.; Unden, A. Tetrahedron Lett., 1995, 36, 9211.
19. 7) Pictet, A.; Spengler, T., Ber. 1911, 44, 1987. For an excellent discussion of the Pictet-Spengler reaction see: Cox. E.; Cook, J. M. Chem. Rev. 1995, 95, 1797.
20. 7) Pictet, A.; Spengler, T., Ber. 1911, 44, 1987. For an excellent discussion of the Pictet-Spengler reaction see: Cox. E.; Cook, J. M. Chem. Rev. 1995, 95, 1797.
21. 8) Wang, S. S. J. Am. Chem. Soc. 1973, 95, 1328.
22. 9) Kaiser, E.; Colescott, R. L.; Bossinger, C. D.; Cook, P. I. Anal. Biochem. 1970, 34, 595.
23. +], calc.: 306.
24. 11) a) Analysis was carried out by HPLC (Vydac C18 column, 4.6 × 250mm, 0-50% acetonitrile/water containing 0.1% TFA) with integration of peak areas at 220nm.
25. b) Mass recoveries were calculated from the weight of crude material and the initial loading level of Fmoc-Trp-Wang resin.
26. 12) In preliminary experiments we have tried to increase diversity within the carboline scaffold through alkylation of the position 2 nitrogen. While activated alkylating reagents such as α-bromomethyl acetate efficiently alkylated some carbolines, this reaction was not reproducible over a wide series of substrates. This chemistry is under investigation.