Synthesis of two conformationally restricted piperazine scaffolds for combinatorial chemistry

European Journal of Organic Chemistry

Volumn , Issue 20, 2004, Pages 4113-4118

  Opatz, Till ^a  

^a JOHANNES GUTENBERG UNIVERSITY   (Germany)

Author keywords

Combinatorial chemistry; Nitrogen heterocycles; Piperazines; Protecting groups; Scaffolds

Indexed keywords

BRIDGED COMPOUND; PIPERAZINE DERIVATIVE;

ARTICLE; CHIRALITY; COMBINATORIAL CHEMISTRY; CONFORMATION; SYNTHESIS;

EID: 8444237129     PISSN: 1434193X     EISSN: None     Source Type: Journal    
DOI: 10.1002/ejoc.200400358     Document Type: Article

References (25)

1. Database: ChemIDplus, Division of Specialized Information Services, National Library of Medicine, USA, http://chem.sis.nlm.nih.gov/chemidplus/.
2. M. Y. Cha, B. C. Choi, K. H. Kang, A. N. Pae, K. I. Choi, Y. S. Cho, H. Y. Koh, H. Y. Lee, D. Jung, J. Y. Kong, Bioorg. Med. Chem. Lett. 2002, 12, 1327-1330.
3. V. S. Goodfellow, C. P. Laudeman, J. I. Gerrity, M. Burkard, E. Strobel, J. S. Zuzack, D. A. McLeod, Mol. Divers. 1996, 2, 97-102.
4. T. F. Herpin, G. C. Morton, A. K. Dunn, C. Fillon, P. R. Menard, S. Y. Tang, J. M. Salvino, R. F. Labaudiniere, Mol. Divers. 1998, 4, 221-232.
5. I. Lewis, B. Rohde, M. Mengus, M. Weetall, S. Maida, R. Hugo, P. Lake, Mol. Divers. 2000, 5, 61-73.
6. For the preparation of a chiral bicyclic piperazine carboxylate scaffold for the construction of cocaine analogues, see: S. Pichlmair, K. Mereiter, U. Jordis, Tetrahedron Lett. 2004, 45, 1481-1483.
7. H. Kurihara, H. Mishima, Heterocycles 1982, 17, 191-199.
8. J. J. N. Veerman, R. S. Bon, B. T. B. Hue, D. Girones, F. P. J. T. Rutjes, J. H. van Maarseveen, H. Hiemstra, J. Org. Chem. 2003, 68, 4486-4494.
9. S. Shiotani, K. Mitsuhashi, Yakugaku Zasshi 1964, 84, 1032-1035.
10. S. Shiotani, K. Mitsuhashi, Yakugaku Zasshi 1966, 86, 169-173.
11. M. E. Freed, J. R. Potoski, E. H. Freed, G. L. Conklin, J. L. Malis, J. Med. Chem. 1973, 16, 595-599.
12. J. L. Malis, M. E. Rosenthale, M. I. Gluckman, J. Pharm. Exp. Ther. 1975, 194, 488-498.
13. E. L. May, E. M. Fry, J. Org. Chem. 1957, 22, 1366-1369.
14. J. F. Cavalla, R. Jones, M. Welford, J. Wax, C. V. Vinder, J. Med. Chem. 1964, 7, 412-415.
15. M. T. Rosseel, M. G. Bogaert, F. M. Belpaire, Curr. Med. Res. Opin. 1975, 3, 181-186.
16. H. Buschmann, T. Christoph, E. Friderichs, C. Maul, B. Sundermann (Eds.), Analgesics, Wiley-VCH, Weinheim, 2002.
17. P. Stelzel, in Synthese von Peptiden, 1512 (Ed.: E. Wünsch), Georg Thieme Verlag, Stuttgart, 1974, pp. 169-259.
18. Attempts to determine the extent of racemization in the coupling step and the subsequent cyclization by chiral HPLC of compounds 6 and 7 were unsuccessful. It should, however, be noted that two samples of compound 16 prepared under different reaction conditions showed identical optical rotations.
19. H. Uchida, T. Kato, K. Achiwa, Chem. Pharm. Bull. 1997, 45, 1228-1230.
20. The dihydropyrazinone is already formed at room temperature, whereas the second cyclization requires elevated temperatures.
21. W. J. Hoekstra, B. E. Maryanoff, B. P. Damiano, P. Andrade-Gordon, J. H. Cohen, M. J. Costanzo, B. J. Haertlein, L. R. Hecker, B. L. Hulshizer, J. A. Kauffman, P. Keane, D. F. McComsey, J. A. Mitchell, L. Scott, R. D. Shah, S. C. Yabut, J. Med. Chem. 1999, 42, 5254-5265.
22. J. Bonjoch, J.-C. Fernandez, N. Valls, J. Org. Chem. 1998, 63, 7338-7347.
23. E. Magnier, Y. Langlois, C. Merienne, Tetrahedron Lett. 1995, 36, 9475-9478.
24. The relative population of the rotamers about the CO-N bond of the Fmoc group is roughly 1:1, whereas there is a marked preference for one of the rotamers about the CO-N bond of the Aloc group (ratio 2:1). The assignment of the conformation of the inconsequential rotamers was not undertaken.
25. V. Schanen, M. P. Cherrier, S. J. deMelo, J. C. Quirion, H. P. Husson, Synthesis 1996, 833-837.