Convergent synthesis of complex diketopiperazines derived from pipecolic acid scaffolds and parallel screening against GPCR targets

Journal of Organic Chemistry

Volumn 71, Issue 23, 2006, Pages 8934-8945

  Dandapani, Sivaraman ^a   Lan, Ping ^a   Beeler, Aaron B ^a   Beischel, Scott ^b   Abbas, Athier ^b,c   Roth, Bryan L ^b,c   Porco Jr , John A ^a   Panek, James S ^a  

^a Boston University   (United States)

^b CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CARBOXYLIC ACIDS; DIMERIZATION; MOLECULAR STRUCTURE; SCANDIUM COMPOUNDS; STEREOCHEMISTRY; SYNTHESIS (CHEMICAL);

AZA-ANNULATION; DIKETOPIPERAZINES (DKP); G-PROTEIN-COUPLED RECEPTORS (GPCRS); PIPECOLIC ACIDS;

NITROGEN COMPOUNDS;

G PROTEIN COUPLED RECEPTOR; LIGAND; MONOMER; PIPECOLIC ACID; PIPERAZINE DERIVATIVE; PIPERAZINEDIONE;

ANNULATION REACTION; ARTICLE; COMPLEX FORMATION; CONVERGENT SYNTHESIS; DIMERIZATION; LIGAND BINDING; MOLECULAR MODEL; STEREOCHEMISTRY; SYNTHESIS;

AZA COMPOUNDS; CATALYSIS; COMBINATORIAL CHEMISTRY TECHNIQUES; CRYSTALLOGRAPHY, X-RAY; DRUG EVALUATION, PRECLINICAL; MODELS, MOLECULAR; MOLECULAR CONFORMATION; PIPECOLIC ACIDS; PIPERAZINES; RECEPTORS, G-PROTEIN-COUPLED; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33750845620     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo061758p     Document Type: Article

References (93)

1. (a) Brevianamide B: Birch, A. J.; Wright, J. J. J. Chem. Soc., Chem. Commun. 1969, 644.
2. (b) Gypsetin: Shinohara, C.; Hasumi, K.; Takei, Y.; Endo, A. J. Antibiot. 1994, 47, 163.
3. (c) Cyclotryprostatin A: Cui, C.-B.; Kakeya, H.; Osada, H. Tetrahedron 1997, 53, 59.
4. (a) Szardenings, A. K.; Harris, D.; Lam, S.; Shi, L.; Tien, D.; Wang, Y.; Patel, D. V.; Navre, M.; Campbell, D. A. J. Med. Chem. 1998, 41, 2194.
5. (b) Guo, T.; Adang, A. E. P.; Dong, G.; Fitzpatrick, D.; Geng, P.; Ho, K.; Jibilian, C. H.; Kultgen, S. G.; Liu, R.; McDonald, E.; Saionz, K. W.; Valenzano, K. J.; van Straten, N. C. R.; Xie, D.; Webb, M. L. Bioorg. Med. Chem. Lett. 2004, 14, 1717.
6. (c) Lin, Q.; Blackwell, H. E. Chem. Commun. 2006, 2884.
7. For reviews on the synthesis and reactivity of DKPs, see: (a) Dinsmore, C. J.; Beshore, D. C. Tetrahedron 2002, 58, 3297.
8. (b) Fischer, P. M. J. Peptide Sci. 2003, 9, 9.
9. (c) Groger, H. Chem. Rev. 2003, 103, 2795.
10. (a) Blaha, K.; Budesinsky, M.; Fric, I.; Smolikova, J.; Vicar, J. Tetrahedron Lett. 1972, 1437.
11. (b) Ong, C. W.; Chang, Y. A.; Wu, J. Y.; Cheng, C. C. Tetrahedron 2003, 59, 8245.
12. (c) Andrei, M.; Romming, C.; Undheim, K. Tetrahedron: Asymmetry 2004, 15, 1359.
13. Huang, H.; Spande, T. F.; Panek, J. S. J. Am. Chem. Soc. 2003, 125, 626.
14. For dimerization strategies to produce chemical libraries, see: (a) Boger, D. L.; Goldberg, J.; Jiang, W.; Chai, W.; Ducray, P.; Lee, J. K.; Ozer, R. S.; Anderson, C. M. Bioorg. Med. Chem. 1998, 6, 1347.
15. (b) Goldberg, J.; Jin, Q.; Ambroise, Y.; Satoh, S.; Desharnais, J.; Capps, K.; Boger, D. L. J. Am. Chem. Soc. 2001, 123, 544.
16. (c) Blackwell, H. E.; demons, P. A.; Schreiber, S. L. Org. Lett. 2001, 3, 1185.
17. (d) Nicolaou, K. C.; Hughes, R.; Cho, S. Y.; Winssinger, N.; Labischinski, H.; Endermann, R. Chem.-Eur. J. 2001, 7, 3824.
18. (e) Schmidt, D. R.; Kwon, O.; Schreiber, S. L. J. Comb. Chem. 2004, 6, 286.
19. Beeler, A. B.; Acquilano, D. E.; Su, Q.; Yan, F.; Roth, B. L.; Panek, J. S.; Porco, J. A., Jr. J. Comb. Chem. 2005, 7, 673.
20. Bertram, A.; Blake, A. J.; Turiso, F. G.; Hannam, J. S.; Jolliffe, K. A.; Pattenden, G.; Skae, M. Tetrahedron 2003, 59, 6979.
21. For select examples, see: (a) Sutherlin, D. P.; Armstrong, R. W. J. Am. Chem. Soc. 1996, 118, 9802.
22. (b) Annis, D. A.; Helluin, O.; Jacobsen, E. N. Angew. Chem., Int. Ed. 1998, 37, 190.
23. (c) Koide, K.; Finkelstein, J. M.; Ball, Z.; Verdine, G. L. J. Am. Chem. Soc. 2001, 123, 398.
24. (d) Stavenger, R. A.; Schreiber, S. L. Angew. Chem., Int. Ed. 2001, 40, 3417.
25. (e) Harrison, B. A.; Gierasch, T.; Neilan, C.; Pasternak, G. W.; Verdine, G. L. J. Am. Chem. Soc. 2002, 124, 13352.
26. (f) Krishnan, S. Schreiber, S. L. Org. Lett. 2004, 6, 4021.
27. For reviews on rare-earth metal Inflates in organic synthesis, see: (a) Kobayashi, S. Synlett 1994, 689.
28. (b) Kobayashi, S. Eur. J. Org. Chem. 1999, 15.
29. (c) Kobayashi, S.; Sugiura, M.; Kitagawa, H.; Lam, W. W.-L. Chem. Rev. 2002, 102, 2227.
30. 3.
31. See Supporting Information for complete experimental details.
32. (a) Ishihara, K.; Kubota, M.; Kurihara, H.; Yamamoto, H. J. Am. Chem. Soc. 1995, 117, 4413.
33. (b) Ishihara, K.; Kobota, M.; Kurihara, H.; Yamamoto, H. J. Org. Chem. 1996, 61, 4560.
34. (a) Ciufolini, M. A.; Deaton, M. V.; Zhu, S.; Chen, M. Tetrahedron 1997, 53, 16299.
35. (b) Aspinall, H. C.; Greeves, N.; Mciver, B. G. Tetrahedron Lett. 1998, 39, 9283.
36. (c) Aspinall, H. C.; Bissett, J. S.; Greeves, N.; Levin, D. Tetrahedron Lett. 2002, 43, 323.
37. (d) Mouhtady, O.; Gaspard-Iloughmane, H.; Roques, N.; Le Rouxa, C. Tetrahedron Lett. 2003, 44, 6379.
38. Kudzin, Z. H.; Lyzwa, P.; Luczak, J. Andrijewski, G. Synthesis 1997, 44.
39. Sonogashira, K. J. Organomet. Chem. 2002, 653, 46.
40. Farina, V.; Krishnamurthy, V.; Scott, W. J. Org. React. 1997, 50, 1.
41. Wolfe, J. P.; Tomori, H.; Sadighi, J. P.; Yin, J.; Buchwald, S. L. J. Org. Chem. 2000, 65, 1158.
42. Klapars, A.; Huang, X.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 7421.
43. For epimerization during peptide coupling with N-trifluoroacetylated amino acids, see: (a) Benourgha, A.; Verducci, J.; Jacquier, R. Bull. Soc. Chim. Fr. 1995, 135, 824.
44. (b) Rajaram, S.; Sigman, M. Org. Lett. 2002, 4, 3399.
45. Mota, A. J.; Castellanos, E.; Juaristi, E. Org. Prep. Proc. Int. 2003, 35, 414.
46. For a comprehensive review of polymeric reagents and scavengers, see: Ley, S. V.; Baxendale, I. R.; Bream, R. N.; Jackson, P. S.; Leach, A. G.; Longbottom, D. A.; Nesi, M.; Scott, S. S.; Storer, R. I.; Taylor, S. J. J. Chem. Soc., Perkin Trans. 1 2000, 3815.
47. (a) Keating, T. A.; Armstrong, R. W. J. Am. Chem. Soc. 1996, 118, 2574.
48. (b) Siegel, M. G.; Hahn, P. J.; Dressman, B. A.; Fritz, J. E.; Grunwell, J. R.; Kaldor, S. W. Tetrahedron Lett. 1997, 38, 3357.
49. For reviews on catch and release using polymer resins, see: (c) Kirschning, A.; Monenschein, H.; Wittenberg, R. Chem.-Eur. J, 2000, 6, 4445.
50. (d) Thompson, L. A. Curr. Opin. Chem. Biol. 2000, 4, 324.
51. (d) Kirschning, A.; Wittenberg, R. Organic Synthesis Highlights V 2003, 265.
52. (a) Reed, L. A., III; Risbood, P. A.; Goodman, L. J. Chem. Soc., Chem. Commun. 1981, 15, 760.
53. (b) Kulkarni, B.; Ganesan, A. Chem. Commun. 1998, 7, 785.
54. (c) Morwick, T. M. J. Comb. Chem. 2006, 8, 649.
55. Sebahar, P. R.; Osada, H.; Usui, T.; Williams, R. W. Tetrahedron 2002, 58, 6311.
56. Sakaitani, M.; Ohfune, Y. J. Org. Chem. 1990, 55, 870.
57. For epimerization during peptide segment coupling, see: (a) Sieber, P.; Kamber, B.; Hartman, A.; Johl, A.; Riniker, B.; Rittel, W. Helv. Chim. Acta 1977, 60, 27.
58. (b) Bodanszky, M. Principles of Peptide Synthesis; Springer-Verlag: Berlin, 1984.
59. For an example of DKP synthesis by coupling of unprotected amino acids, see: Santagada, V.; Fiorino, F.; Perissutti, E.; Severino, B.; Terracciano, S.; Cirino, G.; Caliendo, G. Tetrahedron Lett. 2003, 44, 1145.
60. (a) Carpino, L. A. J. Am. Chem. Soc. 1993, 115, 4397.
61. (b) Carpino, L. A.; El-Faham, A. J. Org. Chem. 1995, 60, 3561.
62. (c) Humphrey, J. M.; Aggen, J. B.; Chamberlin, A. R. J. Am. Chem. Soc. 1996, 118, 11759.
63. (d) Ohshima, T.; Gnanadesikan, V.; Shibuguchi, T.; Fukuta, Y.; Nemoto, T.; Shibasaki, M. J. Am. Chem. Soc. 2003, 125, 11206.
64. Hoffmann, R. W. Chem. Rev. 1989, 89, 1841.
65. (a) Blom, K. F.; Sparks, R.; Doughty, J.; Everlof, G. J.; Haque, T.; Combs, A. P. J. Comb. Chem. 2003, 5, 670.
66. (b) Rosentreter, U.; Huber, U. J. Comb. Chem. 2004, 6, 159.
67. (a) Hanai, T.; Koizumi, K.; Kinoshita, T. J. Liq. Chrom. Relat. Technol. 2000, 23, 363.
68. (b) Djakovic-Sekulic, T.; Acanski, M.; Perisic-Janjic, N. J. Chromatogr. B 2001, 766, 67.
69. (c) Xing, L.; Glen, R. C. J. Chem. Inf. Comput. Sci. 2002, 42, 796.
70. (d) Eros, D.; Kovesdi, I.; Orfi, L.; Novak-Takacs, K.; Acsady, G.; Keri, G. Curr. Med. Chem. 2002, 9, 1819.
71. For a recent publication describing enolization/alkylation of DKPs, see: Davies, S. G.; Rodriguez-Solla, H.; Tamayo, J. A.; Cowley, A. R.; Concellon, C.; Garner, A. C.; Parkes, A. L.; Smith, A. D. Org. Biomol. Chem. 2005, 3, 1435.
72. For an example of DBU-mediated epimerization of an α-alkoxy ester, see: Kadota, I.; Kadowaki, C.; Yoshida, N.; Yamamoto, Y. Tetrahedron Lett. 1998, 39, 6369.
73. All calculations were performed using Spartan 04 for Windows; Wavefunction: Irvine, CA.
74. http://www.spectroscopynow.com/FCKeditor/UserFiles/File/specNOW/ HTML%20files/proton-proton2.htm (accessed August 23, 2006).
75. Armbruster, B. N.; Roth, B. L. J. Biol. Chem. 2005, 280, 5129.
76. O'Connor, K. A.; Roth, B. L. Nat. Rev. Drug Discovery 2005, 4, 1005.
77. Fliri, A. F.; Loging, W. T.; Thadeio, P. F.; Volkmann, R. A. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 261.
78. Melnick, J. S.; Janes, J.; Kim, S.; Chang, J. Y.; Sipes, D. G.; Gunderson, D.; Jarnes, L.; Matzen, J. T.; Garcia, M. E.; Hood, T. L.; Beigi, R.; Xia, G.; Harig, R. A.; Asatryan, H.; Yan, S. F.; Zhou, Y.; Gu, X. J.; Saadat, A.; Zhou, V.; King, F. J.; Shaw, C. M.; Su, A. I.; Downs, R.; Gray, N. S.; Schultz, P. G.; Warmuth, M.; Caldwell, J. S. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 3153.
79. Elphick, G. F.; Querbes, W.; Jordan, J. A.; Gee, G. V.; Eash, S.; Manley, K.; Dugan, A.; Stanifer, M.; Bhatnagar, A.; Kroeze, W. K.; Roth, B. L.; Atwood, W. J. Science 2004, 306, 1380.
80. Roth, B. L.; Baner, K.; Westkaemper, R.; Siebert, D.; Rice, K. C.; Steinberg, S.; Ernsberger, P.; Rothman, R. B. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 11934.
81. Setola, V.; Dukat, M.; Glennon, R. A.; Roth, B. L. Mol. Pharmacol. 2005, 68, 20.
82. Setola, V.; Hufeisen, S. J.; Grande-Allen, K. J.; Vesely, I.; Glennon, R. A.; Blough, B.; Rothman, R. B.; Roth, B. L. Mol. Pharmacol. 2003, 63, 1223.
83. Rothman, R. B.; Baumann, M. H.; Savage, J. E.; Rauser, L.; McBride, A.; Hufeisen, S. J.; Roth, B. L. Circulation 2000, 102, 2836.
84. Borthwick, A. D.; Davies, D. E.; Exall, A. M.; Livermore, D. G.; Sollis, S. L.; Nerozzi, F.; Allen, M. J.; Perren, M.; Shabbir, S. S.; Woollard, P. M.; Wyatt, P. G. J. Med. Chem 2005, 48, 6956.
85. Besada, P.; Mamedova, L.; Thomas, C. J.; Costanzi, S.; Jacobson, K. A. Org. Biomol. Chem 2005, 3, 2016.
86. Prakash, K. R.; Tang, Y.; Kozikowski, A. P.; Flippen-Anderson, J. L.; Knoblach, S. M.; Faden, A. I. Bioorg. Med. Chem. 2002, 10, 3043.
87. Faden, A. I.; Knoblach, S. M.; Cernak, I.; Fan, L.; Vink, R.; Araldi, G. L.; Fricke, S. T.; Roth, B. L.; Kozikowski, A. P. J. Cereb. Blood Flow Metab. 2003, 23, 342.
88. Shapiro, D. A.; Renock, S.; Arlington, E.; Chiodo, L. A.; Liu, L. X.; Sibley, D. R.; Roth, B. L.; Mailman, R. Neuropsychopharmacology 2003, 28, 1400.
89. Rothman, R. B.; Vu, N.; Partilla, J. S.; Roth, B. L.; Hufeisen, S. J.; Compton-Toth, B. A.; Birkes, J.; Young, R.; Glennon, R. A. J. Pharmacol. Exp. Ther. 2003, 307, 138.
90. Shi, Q.; Savage, J. E.; Hufeisen, S. J.; Rauser, L.; Grajkowska, E.; Ernsberger, P.; Wroblewski, J. T.; Nadeau, J. H.; Roth, B. L. J. Pharmacol. Exp. Ther. 2003, 305, 131.
91. Roth, B. L.; Sheffler, D. J.; Kroeze, W. K. Nat. Rev. Drug Discovery 2004, 3, 353.
92. For a recent example of stereochemical influence on biological activity, see: Kim, Y. K.; Arai, M. A.; Arai, T.; Lamenzo, J. O.; Dean, E. F.; Patterson, N.; demons, P. A.; Schreiber, S. L. J. Am. Chem. Soc. 2004, 126, 14740.
93. 13C NMR spectra, X-ray crystal structure analysis for compound 33, and data for Figures 6 and 7 are provided in the Supporting Information.