An efficient two-step synthesis of mono-, di- and triureas from resin- bound amides

Tetrahedron Letters

Volumn 41, Issue 29, 2000, Pages 5441-5446

  Nefzi, Adel ^a   Ong, Nhi A ^a   Houghten, Richard A ^a  

^a TORREY PINES INSTITUTE FOR MOLECULAR STUDIES   (United States)

Author keywords

Combinatorial chemistry; Diurea; Peptidomimetics; Solid phase synthesis; Triurea; Urea

Indexed keywords

AMIDE; DIAMINE; ISOCYANIC ACID DERIVATIVE; MONOAMINE; RESIN; UREA DERIVATIVE;

ACYLATION; ARTICLE; CHEMICAL STRUCTURE; COMPLEX FORMATION; PURIFICATION; SYNTHESIS;

EID: 0034661560     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(00)00845-5     Document Type: Article

References (28)

1. (a) Geysen, H. M.; Meloen, R. H.; Barteling, S. J. Proc. Natl. Acad. Sci. USA 1984, 81, 3998.
2. (b) Houghten, R. A. Proc. Natl. Acad. Sci. USA 1985, 82, 5131.
3. (a) Houghten, R. A.; Pinilla, C.; Blondelle, S. E.; Appel, J. R.; Dooley, C. T.; Cuervo, J. H. Nature 1991, 354, 84-86.
4. (b) Thompson, L. A.; Ellman, J. A. Chem. Rev. 1996, 96, 555.
5. (c) Fruchtel, J. S.; Jung, G. Angew. Chem., Int. Ed. Engl. 1996, 35, 17.
6. (d) Hermkens, P. H. H.; Ottenheijm, H. C. J.; Rees, D. C. Tetrahedron 1996, 52, 4527.
7. (e) Nefzi, A.; Ostresh, J. M.; Houghten, R. A. Chem. Rev. 1997, 97, 449.
8. (a) Dressman, B. A.; Singh, U.; Kaldor, S. W. Tetrahedron Lett. 1998, 39, 3631.
9. (b) Xiao, X-y.; Ngu, K.; Chao, C.; Patel, D. V. J. Org. Chem. 1997, 62, 6968.
10. (c) Wang, G. T.; Chen, Y.; Wang, S.; Sciotti, R.; Sowin, T. Tetrahedron Lett. 1997, 38, 1895.
11. (d) Limal, D.; Semetey, V.; Dalbon, P.; Jolivet, M.; Briand, J.-P. Tetrahedron Lett. 1999, 40, 2749.
12. (e) Norwick, J. S.; Abdi, M.; Bellamo, K. A.; Love, J. A.; Martinez, E. J.; Noroha, G.; Smith, E. M.; Ziller, J. W. J. Am. Chem. Soc. 1995, 117, 89.
13. (f) Hutchins, S. M.; Chapman, K. T. Tetrahedron Lett. 1994, 35, 4055.
14. (g) Burgess, K.; Linthicum, D. S.; Shin, H. Angew. Chem., Int. Ed. Engl. 1995, 34, 907.
15. The MDDR database contains more than 6000 compounds having the urea scaffold.
16. Amagase, K.; Ikeda, K.; Okabe, S. Dig. Dis. Sci. 1999, 44, 879.
17. Tanaka, A.; Terasawa, T.; HaGihara, H.; Sakuma, Y.; Ishibe, N.; Sawada, M.; Takasugi, H.; Tanaka, H. Bioorg. Med. Chem. 1998, 6, 15.
18. Nakao, K.; Shimizu, R.; Hitoshi, K.; Yasuhara, M.; Hashimura, Y.; Suzuki, T.; Fujita, T.; Ohmizu, H. Bioorg. Med. Chem. 1998, 6, 849.
19. (a) Majer, P.; Randad, R. S. J. Org. Chem. 1994, 49, 1937.
20. (b) Norwick, J. S.; Holmes, D. L.; Noronha, G.; Smith, E. M.; Nguyen, T. M.; Huang, S.-L. J. Org. Chem. 1996, 61, 3929.
21. (a) Ostresh, J. M.; Schoner, C. C.; Hamashin, V. T.; Nefzi, A.; Meyer, J.-P.; Houghten, R. A. J. Org. Chem. 1998, 63, 8622.
22. (b) Nefzi, A.; Ostresh, J. M.; Houghten, R. A. Tetrahedron 1999, 55, 335.
23. (c) Nefzi, A.; Ostresh, J. M.; Giulianotti, M.; Houghten, R. A. J. Comb. Chem. 1999, 1, 195.
24. (d) Nefzi, A.; Ostresh, J. M.; Meyer, J.-P.; Houghten, R. A. Tetrahedron Lett. 1997, 38, 931.
25. Yields were ranging from 85 to 98% according to the loading of the resin.
26. Kaiser, E. T.; Colescott, R. L.; Blossinger, C. D.; Cook, P. I. Anal. Biochem. 1970, 34, 595.
27. 6) δ 8.69 (s, 1H), 8.29 (s, 1H), 7.46 (d, J=7.97 Hz, 2H), 7.37 (d, J=8.13 Hz, 2H), 7.28 (m, 4H), 7.21 (m, 5H), 6.92 (t, J=7.10 Hz, 1H), 6.87 (t, J=7.02 Hz, 1H), 6.09 (m, 1H), 3.55 (m, 2H), 3.46 (m, 1H), 3.26 (m, 1H), 2.90 (m, 1H), 2,80 (m, 1H), 1.91 (m, 1H), 0.99 (d, J=6.50 Hz, 3H), 0.86 (d, J=6.49 Hz, 3H).
28. Houghten, R. A.; Pinilla, C.; Appel, J. R.; Blondelle, S. E.; Dooley, C. T.; Eichler, J.; Nefzi, A.; Ostresh, J. M. J. Med. Chem. 1999, 42, 3743.