Trifluoromethyl-substituted imidazolines: Novel precursors of trifluoromethyl ketones amenable to peptide synthesis

Journal of the American Chemical Society

Volumn 118, Issue 35, 1996, Pages 8485-8486

  Derstine, Christopher W ^a   Smith, David N ^a,b   Katzenellenbogen, John A ^a  

^a UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

^b GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; PEPTIDE SYNTHESIS; TECHNIQUE;

EID: 0029836113     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja9614833     Document Type: Article

References (32)

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2. Representative serine proteases. (a) Human neutrophil elastase: Edwards, P. D.; Bernstein, P. R. Med. Res. Rev. 1994, 14, 127-194.
3. (b) α-Chymotrypsin: Imperiali, B.; Abeles, R. H. Biochemistry 1986, 25, 3760-3767.
4. Representative aspartic proteases. (a) HIV protease: Hodge, C. N.; Aldrich, P. E.; Fernandez, C. H.; Otto, M. J.; Rayner, M. M.; Wong, Y. N.; Erickson-Viitanen S. Antiviral Chem. Chemother. 1994, 5, 257-262.
5. (b) Pepsin: Gelb, M. H.; Svaren, J. P.; Abeles, R. H. Biochemistry 1985, 24, 1813-1817.
6. (c) Renin: Patel, D. V.; Rielly-Gauvin, K.; Ryono, D. E.; Free, C. A.; Smith, S. A.; Petrillo, E. D. J. Med. Chem. 1993, 36, 2431-2447.
7. Representative metallo proteases. (a) Angiotensin-converting enzyme: ref 3b.
8. (b) Carboxypeptidase A: ref 3b
9. Representative cysteine proteases. (a) Cathepsin G: Peet, N. P.; Burkhart, J. P.; Angelastro, M. R.; Giroux, E. L.; Mehdi, S.; Bey, P.; Kolb, M. Neises, B. Schirlin, D. J. Med. Chem. 1990, 33, 394-407.
10. (b) Cathepsin B: Smith, R. A.; Copp, L. J.; Donnelly, S. L.; Spencer, R. W.; Krantz, A. Biochemistry 1988, 27, 6568-6573.
11. 3ZnI addition to an isomerically pure peptidyl aldehyde: Edwards, P. D. Tetrahedron Lett. 1992, 33, 4279-4282.
12. (b) Modified Dakin-West procedure: Kolb, M.; Barth, J.; Neises, B. Tetrahedron Lett. 1986, 27, 1579-1582. Kolb, M.; Neises, B. Tetrahedron Lett. 1986, 27, 4437-4440.
13. (b) Modified Dakin-West procedure: Kolb, M.; Barth, J.; Neises, B. Tetrahedron Lett. 1986, 27, 1579-1582. Kolb, M.; Neises, B. Tetrahedron Lett. 1986, 27, 4437-4440.
14. (c) Henry reaction: Imperiali, B.; Abeles, R. H. Tetrahedron Lett. 1986, 27, 135-138.
15. (d) Curtius rearrangement: Patel, D. V.; Gauvin, K. R.; Ryono, D. E. Tetrahedron Lett. 1988, 29, 4665-4668.
16. (a) Achiwa, K.; Sekiya, M. Chem. Lett. 1981, 1213-1216.
17. (b) Achiwa, K.; Motoyama, T.; Sekiya, M. Chem. Pharm. Bull. 1983, 31, 3939-3945.
18. For references on 1,3-dipolar cycloadditions, see: (a) Lown, J. W. In 1,3-Dipolar Cycloaddition Chemistry; Padwa, A., Ed.; Wiley: New York, 1984. (b) Vedejs, E. In Advances in Cycloaddition; Curran, D. P., Ed; JAI: Greenwich, CT, 1988.
19. For references on 1,3-dipolar cycloadditions, see: (a) Lown, J. W. In 1,3-Dipolar Cycloaddition Chemistry; Padwa, A., Ed.; Wiley: New York, 1984. (b) Vedejs, E. In Advances in Cycloaddition; Curran, D. P., Ed; JAI: Greenwich, CT, 1988.
20. (c) Carruthers, W. Cycloaddition Reactions in Organic Synthesis; Pergamon: Oxford, 1990; Chapter 6, pp 269-331.
21. (d) Padwa, A. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 4, Chapter 4.9, pp 1069-1109.
22. (e) Wade, P. A. In Comprehensive Organic Synthesis; Trost, B. M.; Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 4, Chapter 4.10, pp 1111-1168.
23. For reviews of azomethine ylides, see ref 8 and: Terao, Y.; Aono, M.; Achiwa, K. Heterocycles 1988, 27, 981-1008.
24. Trifluoroacetonitrile as a dipolarophile: (a) Kobayashi, Y.; Kumadaki, I.; Kobayashi, E. Heterocycles 1981, 15, 1223-1225.
25. (b) Banks, R. E.; Thompson, J. J. Fluorine Chem. 1983, 22, 589-592.
26. Popowski, E.; Franz, K. Z. Chem. 1979, 19, 103.
27. Since trifluoroacetonitrile (bp -65°C) is a gas, cycloaddition reactions were carried out in stainless steel sample cylinders which were sealed and placed in an oven at the appropriate temperature.
28. Carpino, L. A.; Sadat-Aalaee, D.; Chao, H. G.; DeSelms, R. H. J. Am. Chem. Soc. 1990, 112, 9651-9652. Carpino, L. A.; Mansour, E. M. E.; Sadat-Aalaee, D. J. Org. Chem. 1991, 56, 2611-2614.
29. Carpino, L. A.; Sadat-Aalaee, D.; Chao, H. G.; DeSelms, R. H. J. Am. Chem. Soc. 1990, 112, 9651-9652. Carpino, L. A.; Mansour, E. M. E.; Sadat-Aalaee, D. J. Org. Chem. 1991, 56, 2611-2614.
30. 3-imidazoline, it would appear to be generally useful with Fmoc N-terminal protection/acyl fluoride coupling, using acid labile groups (Boc and trityl) for side chain protection.
31. P. D. Edwards, Zeneca Pharmaceuticals, personal communication.
32. 1 position, it would be necessary to have a general method for the synthesis of substituted α-silylimines. Also, if unsymmetrical α-silylimines and/or azomethine ylides are utilized, it is necessary for the cycloaddition reaction to operate with appropriate regioselectivity, so that the desired substituent would become attached to the C-5 vs the C-2 positions. From our present studies, it appears that the α-silylimine synthesis can be generalized (C. W. Derstine and J. A. Katzenellenbogen, unpublished results), and, at least in the one unsymmetrical case we studied (ca. synthesis of 6), that the cycloaddition can be quite regioselective, although it is not yet certain how selective the cycloaddition will be with the more complex unsymmetrical disubstituted α-silylimines.