Synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid vinyl-ACCA derivatives: Key intermediates for the preparation of inhibitors of the hepatitis C virus NS3 protease

Journal of Organic Chemistry

Volumn 70, Issue 15, 2005, Pages 5869-5879

  Beaulieu, Pierre L ^a   Gillard, James ^a   Bailey, Murray D ^a   Boucher, Colette ^a   Duceppe, Jean Simon ^a   Simoneau, Bruno ^a   Wang, Xiao Jun ^b   Zhang, Li ^b   Grozinger, Karl ^b   Houpis, Ioannis ^b,d   Farina, Vittorio ^b   Heimroth, Heidi ^c   Krueger, Thomas ^c   Schnaubelt, Jürgen ^c  

^a BOEHRINGER INGELHEIM CANADA LTD   (Canada)

^b BOEHRINGER INGELHEIM PHARMACEUTICALS INC   (United States)

^c BOEHRINGER INGELHEIM PHARMA GMBH AND CO KG   (Germany)

^d Eli Lilly Benelux   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACIDS; BUTENES; DERIVATIVES; ENZYMES; GENES; PATIENT TREATMENT; SYNTHESIS (CHEMICAL); VIRUSES;

DIALKYLATION; ENZYMATIC RESOLUTION; ESTERASE ENZYMES; INHIBITORS;

CARBOXYLIC ACIDS;

1 AMINO 2 VINYLCYCLOPROPANECARBOXYLIC ACID; 1 TERT BUTOXYCARBONYLAMINO 2 VINYLCYCLOPROPANECARBOXYLIC ACID ETHYL ESTER; 1 TERT BUTOXYCARBONYLAMINO 2 VINYLCYCLOPROPANECARBOXYLIC ACID METHYL ESTER; 1,4 DIBROMO 2 BUTENE; 7 PHENYL 6,7 DIHYDRO 1H AZEPINE 2 CARBOXYLIC ACID ETHYL ESTER; ANTIVIRUS AGENT; BUTANE; CILUPREVIR; GLYCINE; NS3 PROTEINASE; PEGINTERFERON; PROTEINASE; RIBAVIRIN; SCHIFF BASE; SUBTILISIN; UNCLASSIFIED DRUG; VINYL DERIVATIVE;

ALKYLATION; ARTICLE; DIASTEREOISOMER; DRUG DESIGN; DRUG STRUCTURE; DRUG SYNTHESIS; GENOTYPE; HEPATITIS C VIRUS; SCALE UP; STEREOCHEMISTRY; VIRUS LOAD;

ALKYLATION; AMINO ACIDS, CYCLIC; ANTIVIRAL AGENTS; MODELS, CHEMICAL; PROTEASE INHIBITORS; STEREOISOMERISM; VIRAL NONSTRUCTURAL PROTEINS;

EID: 22244469722     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo050468q     Document Type: Article

References (58)

1. Choo, Q.-L.; Kuo, G.; Weiner, A. J.; Overby, L. R.; Bradley, D. W.; Houghton, M. Science 1989, 244, 359.
2. (a) Di Bisceglie, A. M. Lancet 1998, 351, 351.
3. (b) Wasley, A.; Alter, M. J. Semin. Liver Dis. 2000, 20, 1.
4. (a) Chander, G. Hepatology 2002, 36, S135.
5. (b) Burak, K. W.; Lee, S. S. Can. J. Public Health 2000, 91 (Suppl 1), S22.
6. (c) Zein, C. O.; Zein, N. N. Microbes Infect. 2002, 4, 1237.
7. (a) Beaulieu, P. L.; Llinàs-Brunet, M. Curr. Med. Chem.: Anti-Infect. Agents 2002, 1, 163.
8. (b) McPhee, F.; Yeung, K.-S.; Good, A. C.; Meanwell, N. A. Drugs Future 2003, 28, 465.
9. (a) Tsantrizos, Y. S.; Boler, G.; Bonneau, P.; Cameron, D. R.; Goudreau, N.; Kukolj, G.; LaPlante, S. R.; Llinàs-Brunet, M.; Nar, H.; Lamarre, D. Angew. Chem., Int. Ed. 2003, 42, 1356.
10. (b) Llinàs-Brunet, M.; Bailey, M. D.; Bolger, G.; Brochu, C.; Faucher, A.-M.; Ferland, J.-M.; Garneau, M.; Ghiro, E.; Gorys, V.; Grand-Maître, C.; Halmos, T.; Lapeyre-Paquette, N.; Liard, F.; Poirier, M.; Rhéaume, M.; Tsantrizos, Y. S.; Lamarre, D. J. Med. Chem. 2004, 47, 1605.
11. (c) Lamarre, D.; Anderson, P. C.; Bailey, M.; Beaulieu, P.; Bolger, G.; Bonneau, P.; Bös, M.; Cameron, D.; Cartier, M.; Cordingley, M. G.; Faucher, A.-M.; Goudreau, N.; Kawai, S. H.; Kukolj, G.; Lagacé, L.; LaPlante, S. R.; Narjes, H.; Poupart, M.-A.; Rancourt, J.; Sentjens, R. E.; St-George, R.; Simoneau, B.; Steinmann, G.; Thibeault, D.; Tsantrizos, Y. S.; Weldon, S. M.; Yong, C.-L.; Llinàs-Brunet, M. Nature 2003, 426, 186.
12. Hinrichsen, H.; Benhamou, Y.; Wedemeyer, H.; Reiser, M.; Sentjens, R. E.; Calleja, J. L.; Forns, X.; Erhardt, A.; Cröenlein, J.; Chaves, R.; Yong, C.-L.; Nehmiz, G.; Steinmann, G. G. Gastroenterology 2004, 127, 1347.
13. Faucher, A.-M.; Bailey, M. D.; Beaulieu, P. L.; Brochu, C.; Duceppe, J.-S.; Ferland, J.-M.; Ghiro, E.; Gorys, V.; Halmos, T.; Kawai, S. H.; Poirier, M.; Simoneau, B.; Tsantrizos, Y. S.; Llinàs-Brunet, M. Org. Lett. 2004, 6, 2901.
14. Rancourt, J.; Cameron, D. R.; Gorys, V.; Lamarre, D.; Poirier, M.; Thibeault, D.; Llinàs-Brunet, M. J. Med. Chem. 2004, 47, 2511.
15. Since the initial discovery that vinyl-ACCA confers exceptional potency when incorporated in the P1 position of peptidomimetic-based HCV protease inhibitors (Llinas-Brunet, M.; Bailey, M. D.; Cameron, D. R.; Faucher, A.-M.; Ghiro, E.; Goudreau, N.; Halmos, T.; Poupart, M.-A.; Rancourt, J.; Tsantrizos, Y. S.; Wernic, D.; Simoneau, B. PCT Int. Appl. 2000, WO 00/09543 A2), others have since adopted the use of this fragment and derivatives thereof for the design of HCV protease inhibitors.
16. See for example: (a) Campbell, J. A.; Good, A. PCT Int. Appl. 2002, WO 02/060926 A2.
17. (b) Wang, X.-d. A.; Sun, L.-Q.; Sit, S,-Y.; Sin, N.; Scola, P. M.; Hewawasam, P.; Good, A. C.; Chen, Y.; Campbell, J. A. PCT Int. Appl. 2003, WO 03/099274 A1.
18. (c) Miao, Z.; Sun, Y.; Wu, F.; Nakajima, S.; Xu, G.; Or, Y. S.; Wang, Z. PCT Int. Appl. 2004, WO 04/072243 A2.
19. Salaün, J. Top. Curr. Chem. 2000, 207, 1.
20. (a) Jiménez, J. M.; Rifé, J.; Ortuño, R. M. Tetrahedron: Asymmetry 1996, 7, 537.
21. (b) Cativiela, C.; Díaz-de-Villegas, M. D.; Jiménez, A. I. Tetrahedron: Asymmetry 1995, 6, 177.
22. (c) Fliche, C.; Braun, J.; Le Goffic, F. Synth. Commun. 1994, 24, 2873.
23. (a) Park, K.-H.; Kurth, T. M.; Olmstead, M. M.; Kurth, M. J. Tetrahedron Lett. 2001, 42, 991.
24. (b) Dorizon, P.; Su, G.; Ludvig, G.; Nikitina, L.; Ollivier, J.; Salaün, J. Synlett 1998, 483.
25. (c) Paugam, R.; Gaucher, A.; Dorizon, P.; Ollivier, J.; Salaün, J. Tetrahedron 2000, 56, 8495.
26. O'Donnell, M. J.; Bennett, W. D.; Bruder, W. A.; Jacobsen, W. N.; Knuth, K.; LeClef, B.; Polt, R. L.; Bordwell, F. G.; Mrozack, S. R.; Cripe, T. A. J. Am. Chem. Soc. 1988, 110, 8520.
27. See for example: (a) O'Donnell, M. J.; Bennett, W. D.; Wu, S. J. Am. Chem. Soc. 1989, 111, 2353.
28. (b) O'Donnell, M. J.; Wu, S.; Huffman, J. C. Tetrahedron 1994, 50, 4507.
29. (c) O'Donnell, M. J.; Delgado, F.; Hostettler, C.; Schwesinger, R. Tetrahedron Lett. 1998, 39, 8775.
30. (d) Lygo, B.; Wainwright, P. G. Tetrahedron Lett. 1997, 38, 8595.
31. (e) Corey, E. J.; Xu, F.; Noe, M. C. J. Am. Chem. Soc. 1997, 119, 12414.
32. (f) Corey, E. J.; Noe, M. C.; Xu, F. Tetrahedron Lett. 1998, 39, 5347.
33. The synthesis of 1-aminocyclopropane-1-carboxylic acid via bis-alkylation of a glycine-benzophenone imine was recently reported: Allwein, S. P.; Secord, E. A.; Martins, A.; Mitten, J. V.; Nelson, T. D.; Kress, M. H.; Dolling, U. H. Synlett 2004, 2489.
34. (a) O'Donnell, M. J.; Wu, S. Tetrahedron: Asymmetry 1992, 3, 587.
35. (b) Lygo, B.; Crosby, J.; Peterson, J. A. Tetrahedron Lett. 1999, 40, 8671.
36. (c) Belokon', Y. N.; Kochetkov, K. A.; Churkina, T. D.; Ikonnikov, N. S.; Chesnokov, A. A.; Larionov, O. V.; Parmár, V. S.; Kumar, R.; Kagan, H. B. Tetrahedron: Asymmetry 1998, 9, 851.
37. (d) Belokon', Y. N.; Kochetkov, K. A.; Churkina, T. D.; Ikonnikov, N. S.; Vyskocil, S.; Kagan, H. B. Tetrahedron: Asymmetry 1999, 10, 1723.
38. (e) Belokon', Y. N.; Davies, R. G.; North, M. Tetrahedron Lett. 2000, 41, 7245.
39. (f) Belokon', Y. N.; Kochetkov, K. A.; Churkina, T. D.; Ikonnikov, N. S.; Chesnokov, A. A.; Larionov, O. V.; Singh, I.; Parmar, V. S.; Vyskocyl, S.; Kagan, H. B. J. Org. Chem. 2000, 65, 7041.
40. (g) Belokon', Y. N.; Bhave, D.; D'Addario, D.; Groaz, E.; Maleev, V.; North, M.; Pertrosyan, A. Tetrahedron Lett. 2003, 44, 2045.
41. (h) Ooi, T.; Takeuchi, M.; Kameda, M.; Maruoka, K. J. Am. Chem. Soc. 2000, 122, 5228.
42. Haddow, J.; Suckling, C. J.; Wood, H. C. S. J. Chem. Soc., Perkin Trans. 1 1989, 1297.
43. Amino ester 7 is partially soluble in water and volatile under reduced pressure. Special precautions such as saturating aqueous phases with NaCl and evaporating organic solutions of 7 at room temperature under reduced pressure must be taken to ensure good recovery of the material.
44. O'Donnell, M. J.; Polt, R. L. J. Org. Chem. 1982, 47, 2663.
45. N2′ displacements have been observed in other systems; see for example: Boeckman, R. K., Jr.; Reeder, M. R. J. Org. Chem. 1997, 62, 6456.
46. Wiliams, R. M.; Glinka, T.; Kwast, E. J. Am. Chem. Soc. 1988, 110, 5927. Such behaviors can be ascribed to the existence of tight aggregational states of the enolate in nonpolar solvents: (diagram presented)
47. Keegstra, M. A.; Verkruijsse, H. D.; Andringa, H.; Brandsma, L. Synth. Commun. 1991, 21, 721.
48. Mixtures of imine 4 and 1,4-dibromo-2-butene generate small amounts of a white precipitate upon standing in toluene at room temperature. The solid was identified as glycine ethyl ester hydrobromide.
49. (a) Enzymes in Synthetic Organic Chemistry; Wong, C. H., Whitesides, G. M., Eds.; Elsevier Science, Inc.: New York, 1994.
50. (b) Enzyme Catalysis in Organic Synthesis. A Comprehensive Handbook; Drauz, K., Waldmann, H., Eds.; VCH Publishers: New York, 1995; Vol. 1.
51. See for example: (a) Weiguo, L.; Ray, P.; Benezra, S. A. J. Chem. Soc., Perkin Trans. 1 1995, 553.
52. (b) Spero, D. M.; Kapadia, S. R. J. Org. Chem. 1996, 61, 7398.
53. (c) Kaptein, B.; Boesten, W. H. J.; Broxterman, Q. B.; Peters, P. J. H.; Schoemaker, H. E.; Kamphuis, J. Tetrahedron: Asymmetry 1993, 4, 1113.
54. (d) Weiguo, L. Application of Biocatalysis in Chemical Process Development: A Few Case Studies; ACS Symposium Series 776; American Chemical Society: Washington, DC, 2001; p 178.
55. Bailey, M. D.; Halmos, T.; Adamson, D.; Bordeleau, J.; Grand-Maître, C.; Tetrahedron: Asymmetry 1999, 10, 3285.
56. Beaulieu, P. L.; Gillard, J.; Bailey, M.; Beaulieu, C.; Duceppe, J.-S.; Lavallée, P.; Wernic, D. J. Org. Chem. 1999, 64, 6622.
57. Charette, A. B.; Côté, B. J. Am. Chem. Soc. 1995, 117, 12721.
58. Bonneau, P. R.; Eyer, M.; Graycar, T. P.; Estell, D. A.; Jones, J. B. Bioorg. Chem. 1993, 21, 431.