Elevated conformational rigidity in dipeptides incorporating piperazic acid derivatives

Journal of the American Chemical Society

Volumn 120, Issue 1, 1998, Pages 80-86

  Xi, Ning ^a   Alemany, Lawrence B ^a   Ciufolini, Marco A ^a  

^a RICE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DIPEPTIDE; PIPERAZINE DERIVATIVE;

ARTICLE; CHIRALITY; CRYSTAL STRUCTURE; DRUG SYNTHESIS; INFRARED SPECTROPHOTOMETRY; MASS SPECTROMETRY; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PROTEIN STRUCTURE; RIGIDITY;

EID: 0032515431     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja9729903     Document Type: Article

References (42)

1. Cf. (a) Regan, L.; DeGrado, W. F. Science 1988, 241, 976. (b) Hecht, M. H.; Richardson, J. S.; Richardson, D. C.; Ogden, R. C. Science 1990, 249, 884. (c) Osterhout, J. J., Jr.; Handel, T.; Na, G.; Arazdordi, T.; Long, R. C.; Connolly, P. J.; Hoch, J. C.; Johnson, W. C. Jr., Live, D.; DeGrado, W. F. J. Am. Chem. Soc. 1992, 114, 331.
2. Cf. (a) Regan, L.; DeGrado, W. F. Science 1988, 241, 976. (b) Hecht, M. H.; Richardson, J. S.; Richardson, D. C.; Ogden, R. C. Science 1990, 249, 884. (c) Osterhout, J. J., Jr.; Handel, T.; Na, G.; Arazdordi, T.; Long, R. C.; Connolly, P. J.; Hoch, J. C.; Johnson, W. C. Jr., Live, D.; DeGrado, W. F. J. Am. Chem. Soc. 1992, 114, 331.
3. Cf. (a) Regan, L.; DeGrado, W. F. Science 1988, 241, 976. (b) Hecht, M. H.; Richardson, J. S.; Richardson, D. C.; Ogden, R. C. Science 1990, 249, 884. (c) Osterhout, J. J., Jr.; Handel, T.; Na, G.; Arazdordi, T.; Long, R. C.; Connolly, P. J.; Hoch, J. C.; Johnson, W. C. Jr., Live, D.; DeGrado, W. F. J. Am. Chem. Soc. 1992, 114, 331.
4. Cf. Smith, C. K.; Regan, L. Acc. Chem. Res. 1997, 30, 153.
5. Cf. (a) Creighton, T. E. Proteins: Structure and Molecular Properties; Freeman: New York, 1983. (b) Rizo, J.; Gierasch, L. Annu. Rev. Biochem. 1992, 61, 387. (c) Rose, G. D.; Gierasch, L. M.; Smith, J. A. Adv. Protein Chem. 1985, 37, 1. (d) Ferguson, M. D.; Meara, J. P.; Nakanishi, H.; Lee, M. S.; Kahn, M. Tetrahedron Lett. 1997, 38, 6961 and references cited therein.
6. Cf. (a) Creighton, T. E. Proteins: Structure and Molecular Properties; Freeman: New York, 1983. (b) Rizo, J.; Gierasch, L. Annu. Rev. Biochem. 1992, 61, 387. (c) Rose, G. D.; Gierasch, L. M.; Smith, J. A. Adv. Protein Chem. 1985, 37, 1. (d) Ferguson, M. D.; Meara, J. P.; Nakanishi, H.; Lee, M. S.; Kahn, M. Tetrahedron Lett. 1997, 38, 6961 and references cited therein.
7. Cf. (a) Creighton, T. E. Proteins: Structure and Molecular Properties; Freeman: New York, 1983. (b) Rizo, J.; Gierasch, L. Annu. Rev. Biochem. 1992, 61, 387. (c) Rose, G. D.; Gierasch, L. M.; Smith, J. A. Adv. Protein Chem. 1985, 37, 1. (d) Ferguson, M. D.; Meara, J. P.; Nakanishi, H.; Lee, M. S.; Kahn, M. Tetrahedron Lett. 1997, 38, 6961 and references cited therein.
8. Cf. (a) Creighton, T. E. Proteins: Structure and Molecular Properties; Freeman: New York, 1983. (b) Rizo, J.; Gierasch, L. Annu. Rev. Biochem. 1992, 61, 387. (c) Rose, G. D.; Gierasch, L. M.; Smith, J. A. Adv. Protein Chem. 1985, 37, 1. (d) Ferguson, M. D.; Meara, J. P.; Nakanishi, H.; Lee, M. S.; Kahn, M. Tetrahedron Lett. 1997, 38, 6961 and references cited therein.
9. One of the earliest examples of the turn-forming ability of N-acyl proline dipeptides composed of amino acids of opposite configurations ("heterochiral sequences") may be found in the structure of gramicidin: Hull, S. E.; Karlsson, R.; Main, P.; Woolfson, M. M.; Dodson, E. J. Nature 1978, 275, 206. An excellent discussion of the turn-forming ability of heterochiral sequences appears in ref 3c, p 22 ff. a
10. Alternative techniques used to stabilize turns may include formation of disulfide bridges (cf. Quinn, T. P.; Tweedy, N. B.; Williams, R. W.; Richardson, J. S.; Richardson, D. C. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 8747) or metal ligation (cf. Handel, T. M.; Williams, S. A.; DeGrado, W. F. Science 1993, 261, 879). In extreme cases, a rigid scaffolding resembling the environment of turns has been used to enforce a desired conformation: e.g., Kim, K.; Germanas, J. P. J. Org. Chem. 1997, 62, 2847, 2853. Lombart, H. G.; Lubell, W. D. J. Org. Chem. 1996, 61, 9437.
11. Alternative techniques used to stabilize turns may include formation of disulfide bridges (cf. Quinn, T. P.; Tweedy, N. B.; Williams, R. W.; Richardson, J. S.; Richardson, D. C. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 8747) or metal ligation (cf. Handel, T. M.; Williams, S. A.; DeGrado, W. F. Science 1993, 261, 879). In extreme cases, a rigid scaffolding resembling the environment of turns has been used to enforce a desired conformation: e.g., Kim, K.; Germanas, J. P. J. Org. Chem. 1997, 62, 2847, 2853. Lombart, H. G.; Lubell, W. D. J. Org. Chem. 1996, 61, 9437.
12. Alternative techniques used to stabilize turns may include formation of disulfide bridges (cf. Quinn, T. P.; Tweedy, N. B.; Williams, R. W.; Richardson, J. S.; Richardson, D. C. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 8747) or metal ligation (cf. Handel, T. M.; Williams, S. A.; DeGrado, W. F. Science 1993, 261, 879). In extreme cases, a rigid scaffolding resembling the environment of turns has been used to enforce a desired conformation: e.g., Kim, K.; Germanas, J. P. J. Org. Chem. 1997, 62, 2847, 2853. Lombart, H. G.; Lubell, W. D. J. Org. Chem. 1996, 61, 9437.
13. Alternative techniques used to stabilize turns may include formation of disulfide bridges (cf. Quinn, T. P.; Tweedy, N. B.; Williams, R. W.; Richardson, J. S.; Richardson, D. C. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 8747) or metal ligation (cf. Handel, T. M.; Williams, S. A.; DeGrado, W. F. Science 1993, 261, 879). In extreme cases, a rigid scaffolding resembling the environment of turns has been used to enforce a desired conformation: e.g., Kim, K.; Germanas, J. P. J. Org. Chem. 1997, 62, 2847, 2853. Lombart, H. G.; Lubell, W. D. J. Org. Chem. 1996, 61, 9437.
14. Struthers, M. D.; Cheng, R. P.; Imperiali, B. Science 1996, 271, 342.
15. Ciufolini, M. A.; Xi, N. J. Org. Chem. 1997, 62, 2320.
16. Luzopeptins: (a) Konishi, M.; Ohkuma, H.; Sakai, F.; Tsuno, T.; Koshiyama, H.; Naito, T.; Kawaguchi, H. J. Am. Chem. Soc. 1981, 103, 1241. (b) Arnold, E.; Clardy, J. J. Am. Chem. Soc. 1981, 103, 1243 and references therein. Quinoxapeptins: (c) Lingham, R. B.; Hsu, A. H. M.; O'Brien, J. A.; Sigmund, J. M.; Sanchez, M.; Gagliardi, M. M.; Heimbuch, B. K.; Genilloud, O.; Martin, I.; Diez, M. T.; Hirsch, C. F.; Zink, D. L.; Liesch, J. M.; Koch, G. E.; Gartner, S. E.; Garrity, G. M.; Tsou, N. N.; Salituro, G. M. J. Antibiot. 1996, 49, 253. We propose the convenient descriptor "peptins" to refer to the entire class of these antibiotics.
17. Luzopeptins: (a) Konishi, M.; Ohkuma, H.; Sakai, F.; Tsuno, T.; Koshiyama, H.; Naito, T.; Kawaguchi, H. J. Am. Chem. Soc. 1981, 103, 1241. (b) Arnold, E.; Clardy, J. J. Am. Chem. Soc. 1981, 103, 1243 and references therein. Quinoxapeptins: (c) Lingham, R. B.; Hsu, A. H. M.; O'Brien, J. A.; Sigmund, J. M.; Sanchez, M.; Gagliardi, M. M.; Heimbuch, B. K.; Genilloud, O.; Martin, I.; Diez, M. T.; Hirsch, C. F.; Zink, D. L.; Liesch, J. M.; Koch, G. E.; Gartner, S. E.; Garrity, G. M.; Tsou, N. N.; Salituro, G. M. J. Antibiot. 1996, 49, 253. We propose the convenient descriptor "peptins" to refer to the entire class of these antibiotics.
18. Luzopeptins: (a) Konishi, M.; Ohkuma, H.; Sakai, F.; Tsuno, T.; Koshiyama, H.; Naito, T.; Kawaguchi, H. J. Am. Chem. Soc. 1981, 103, 1241. (b) Arnold, E.; Clardy, J. J. Am. Chem. Soc. 1981, 103, 1243 and references therein. Quinoxapeptins: (c) Lingham, R. B.; Hsu, A. H. M.; O'Brien, J. A.; Sigmund, J. M.; Sanchez, M.; Gagliardi, M. M.; Heimbuch, B. K.; Genilloud, O.; Martin, I.; Diez, M. T.; Hirsch, C. F.; Zink, D. L.; Liesch, J. M.; Koch, G. E.; Gartner, S. E.; Garrity, G. M.; Tsou, N. N.; Salituro, G. M. J. Antibiot. 1996, 49, 253. We propose the convenient descriptor "peptins" to refer to the entire class of these antibiotics.
19. Compound 4 was obtained by Schreiber ozonolysis of cyclopentene to methyl 5-oxopentanoate (Claus, R. E.; Schreiber, S. L. Organic Syntheses; Wiley: New York, 1990; Collect. Vol. VII, p 168) followed by ketalization, hydrolysis, and coupling to the Evans auxiliary. Relevant references for key steps: (step a) Gennari, C.; Colombo, L.; Bertolini, G. J. Am. Chem. Soc. 1986, 108, 6394. Evans, D. A.; Britton, T. C.; Dorow, R. L.; Dellaria, J. F. J. Am. Chem. Soc. 1986, 108, 6395. Trimble, L. A.; Vederas, J. C. J. Am. Chem. Soc. 1986, 108, 6397. (Step b) Evans, D. A.; Britton, T. C.; Dorow, R. L.; Dellaria, J. F. Tetrahedron 1988, 44, 5525. (Steps c and d) see refs 7 and 10. (Steps g and h) Ishizuka, T.; Kunieda, T. Tetrahedron Lett. 1987, 28, 4185.
20. Compound 4 was obtained by Schreiber ozonolysis of cyclopentene to methyl 5-oxopentanoate (Claus, R. E.; Schreiber, S. L. Organic Syntheses; Wiley: New York, 1990; Collect. Vol. VII, p 168) followed by ketalization, hydrolysis, and coupling to the Evans auxiliary. Relevant references for key steps: (step a) Gennari, C.; Colombo, L.; Bertolini, G. J. Am. Chem. Soc. 1986, 108, 6394. Evans, D. A.; Britton, T. C.; Dorow, R. L.; Dellaria, J. F. J. Am. Chem. Soc. 1986, 108, 6395. Trimble, L. A.; Vederas, J. C. J. Am. Chem. Soc. 1986, 108, 6397. (Step b) Evans, D. A.; Britton, T. C.; Dorow, R. L.; Dellaria, J. F. Tetrahedron 1988, 44, 5525. (Steps c and d) see refs 7 and 10. (Steps g and h) Ishizuka, T.; Kunieda, T. Tetrahedron Lett. 1987, 28, 4185.
21. Compound 4 was obtained by Schreiber ozonolysis of cyclopentene to methyl 5-oxopentanoate (Claus, R. E.; Schreiber, S. L. Organic Syntheses; Wiley: New York, 1990; Collect. Vol. VII, p 168) followed by ketalization, hydrolysis, and coupling to the Evans auxiliary. Relevant references for key steps: (step a) Gennari, C.; Colombo, L.; Bertolini, G. J. Am. Chem. Soc. 1986, 108, 6394. Evans, D. A.; Britton, T. C.; Dorow, R. L.; Dellaria, J. F. J. Am. Chem. Soc. 1986, 108, 6395. Trimble, L. A.; Vederas, J. C. J. Am. Chem. Soc. 1986, 108, 6397. (Step b) Evans, D. A.; Britton, T. C.; Dorow, R. L.; Dellaria, J. F. Tetrahedron 1988, 44, 5525. (Steps c and d) see refs 7 and 10. (Steps g and h) Ishizuka, T.; Kunieda, T. Tetrahedron Lett. 1987, 28, 4185.
22. Compound 4 was obtained by Schreiber ozonolysis of cyclopentene to methyl 5-oxopentanoate (Claus, R. E.; Schreiber, S. L. Organic Syntheses; Wiley: New York, 1990; Collect. Vol. VII, p 168) followed by ketalization, hydrolysis, and coupling to the Evans auxiliary. Relevant references for key steps: (step a) Gennari, C.; Colombo, L.; Bertolini, G. J. Am. Chem. Soc. 1986, 108, 6394. Evans, D. A.; Britton, T. C.; Dorow, R. L.; Dellaria, J. F. J. Am. Chem. Soc. 1986, 108, 6395. Trimble, L. A.; Vederas, J. C. J. Am. Chem. Soc. 1986, 108, 6397. (Step b) Evans, D. A.; Britton, T. C.; Dorow, R. L.; Dellaria, J. F. Tetrahedron 1988, 44, 5525. (Steps c and d) see refs 7 and 10. (Steps g and h) Ishizuka, T.; Kunieda, T. Tetrahedron Lett. 1987, 28, 4185.
23. Compound 4 was obtained by Schreiber ozonolysis of cyclopentene to methyl 5-oxopentanoate (Claus, R. E.; Schreiber, S. L. Organic Syntheses; Wiley: New York, 1990; Collect. Vol. VII, p 168) followed by ketalization, hydrolysis, and coupling to the Evans auxiliary. Relevant references for key steps: (step a) Gennari, C.; Colombo, L.; Bertolini, G. J. Am. Chem. Soc. 1986, 108, 6394. Evans, D. A.; Britton, T. C.; Dorow, R. L.; Dellaria, J. F. J. Am. Chem. Soc. 1986, 108, 6395. Trimble, L. A.; Vederas, J. C. J. Am. Chem. Soc. 1986, 108, 6397. (Step b) Evans, D. A.; Britton, T. C.; Dorow, R. L.; Dellaria, J. F. Tetrahedron 1988, 44, 5525. (Steps c and d) see refs 7 and 10. (Steps g and h) Ishizuka, T.; Kunieda, T. Tetrahedron Lett. 1987, 28, 4185.
24. Compound 4 was obtained by Schreiber ozonolysis of cyclopentene to methyl 5-oxopentanoate (Claus, R. E.; Schreiber, S. L. Organic Syntheses; Wiley: New York, 1990; Collect. Vol. VII, p 168) followed by ketalization, hydrolysis, and coupling to the Evans auxiliary. Relevant references for key steps: (step a) Gennari, C.; Colombo, L.; Bertolini, G. J. Am. Chem. Soc. 1986, 108, 6394. Evans, D. A.; Britton, T. C.; Dorow, R. L.; Dellaria, J. F. J. Am. Chem. Soc. 1986, 108, 6395. Trimble, L. A.; Vederas, J. C. J. Am. Chem. Soc. 1986, 108, 6397. (Step b) Evans, D. A.; Britton, T. C.; Dorow, R. L.; Dellaria, J. F. Tetrahedron 1988, 44, 5525. (Steps c and d) see refs 7 and 10. (Steps g and h) Ishizuka, T.; Kunieda, T. Tetrahedron Lett. 1987, 28, 4185.
25. Cf. Ciufolini, M. A.; Xi, N. Tetrahedron Lett. 1995, 36, 6595.
26. + calculations are of qualitative, rather than quantitative, significance. We relied primarily on PM3 semiempirical methods, because this technique seems to reproduce experimental conformational population ratios rather well.
27. Repulsive forces are not as strong in PM3, a reparametrized form of AM1, as they are in other semiempirical methods (Hyperchem literature and manuals). Therefore the conformational energy differences calculated by this method are likely to represent lower-end estimates.
28. Blount, J. F.; Dunlop, R. W.; Erickson, K. L.; Wells, R. J. Aust. J. Chem. 1982, 35, 5, 145.
29. We are grateful to one of the reviewers for kindly bringing to our attention the work cited in refs 13, 17, and 20.
30. (a) Davies, D. B.; Abu Khaled, M.; Urry, D. W. J. Chem. Soc., Perkin Trans. 2 1977, 1294.
31. (b) Hayamizu, K.; Yamamoto, O. J. Mol. Spectrosc. 1967, 22, 119.
32. (c) Riggs, N. V.; Verma, S. M. Tetrahedron Lett. 1968, 19, 3767.
33. (a) Mersh, J. D.; Sanders, J. K. M. J. Magn. Reson. 1982, 50, 289.
34. (b) Hosur, R. V.; Ernst, R. R.; Wüthrich, K. J. Magn. Reson. 1983, 54, 142.
35. (c) Freeman, R. A Handbook of Nuclear Magnetic Resonance; John Wiley & Sons: New York, 1988; pp 14-16.
36. Bock, M. G.; DiPardo, R. M.; Williams, P. D.; Pettibone, D. J.; Clineschmidt, B. V.; Ball, R. G.; Veber, D. F.; Freidiger, R. M. J. Med. Chem. 1990, 33, 2321.
37. For a discussion of the ability of depsipeptides to establish turn motifs, see: Haque, T. S.; Little, J. C.; Gellman, S. H. J. Am. Chem. Soc. 1996, 218, 6915.
38. Cf. Stille, J. K.; Becker, Y. J. Org. Chem. 1980, 45, 2139.
39. Results of more sophisticated ab initio calculations concerning charge distribution and rotational barriers in various carbonyl compounds may be found in the following: (a) Wiberg, K. B.; Laidig, K. E. J. Am. Chem. Soc. 1987, 109, 5935. (b) Laidig, K. E.; Cameron, L. M. Can. J. Chem. 1993, 71, 872. These methods may permit calculation of rotational barriers in PCA peptides; however, we have not yet carried out such studies.
40. Results of more sophisticated ab initio calculations concerning charge distribution and rotational barriers in various carbonyl compounds may be found in the following: (a) Wiberg, K. B.; Laidig, K. E. J. Am. Chem. Soc. 1987, 109, 5935. (b) Laidig, K. E.; Cameron, L. M. Can. J. Chem. 1993, 71, 872. These methods may permit calculation of rotational barriers in PCA peptides; however, we have not yet carried out such studies.
41. After the submission of this paper the preparation of the remarkable ring system 24 was described: Mish, M. R.; Guerra, F. M.; Carreira, E. M. J. Am. Chem. Soc. 1997, 119, 8379.
42. 2.