Solution-phase simultaneous addition of functionalities (SPSAF) and chemical transformation to prepare N,N'-disubstituted piperazine libraries

Biotechnology and Bioengineering

Volumn 61, Issue 2, 1998, Pages 119-125

  Kung, Pei Pei ^a   Cook, P Dan ^a  

^a ISIS PHARMACEUTICALS   (United States)

Author keywords

Antimicrobial activity; Piperazine libraries; Solution phase addition of functionalities

Indexed keywords

ANTIBIOTICS; BACTERIA; BIOCHEMISTRY; ESCHERICHIA COLI; MOLECULAR STRUCTURE;

ANTIMICROBIAL ACTIVITY; COMBINATORIAL CHEMISTRY; PIPERAZINE LIBRARY; SOLUTION PHASE SIMULTANEOUS ADDITION OF FUNCTIONALITIES; SOLUTION PHASE SYNTHESIS;

BIOSYNTHESIS;

DRUG CARRIER; FUNCTIONAL GROUP; PIPERAZINE DERIVATIVE;

ANTIMICROBIAL ACTIVITY; AQUEOUS SOLUTION; ARTICLE; CHEMICAL REACTION; DRUG SCREENING; DRUG SYNTHESIS; ESCHERICHIA COLI; GRAM NEGATIVE BACTERIUM; GRAM POSITIVE BACTERIUM; MASS SPECTROMETRY; STREPTOCOCCUS PYOGENES;

ANTI-BACTERIAL AGENTS; BOROHYDRIDES; ESCHERICHIA COLI; MASS SPECTROMETRY; PEPTIDE LIBRARY; PIPERAZINES; STREPTOCOCCUS PYOGENES; TECHNOLOGY, PHARMACEUTICAL;

BACTERIA (MICROORGANISMS); ESCHERICHIA COLI; NEGIBACTERIA; POSIBACTERIA; STREPTOCOCCUS PYOGENES;

EID: 0032029575     PISSN: 00063592     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1097-0290(199821)61:2<119::AID-BIT6>3.0.CO;2-P     Document Type: Article

References (20)

1. (a) Bunin, B. A.; Ellman, J. A. J. Am. Chem. Soc. 1992, 114, 10997.
2. (b) Dewitt, S. H., Kiely, J. S.; Stankovic, C. J.; Schroeder, M. C.; Reynolds, D. M.; Cody, M. R; Pavia, X. X. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 6909.
3. (c) Bunin, B. A.; Plunkett, M. J.; Ellman, J. A. Proc. Natl. Acad. Sci. U.S.A 1994, 91, 4708.
4. (d) Kurth, M. J.; Jones, A. D.; Miller, R. B.; Alberg, L. A.; Randall, C. J.; Chen J. Am. Chem. Soc. 1994, 116, 2661.
5. (a) Backes, B. J.; Ellman, J. A. J. Am. Chem. Soc. 1994, 116, 11171.
6. (b) Burgess, K.; Linthicum, D.S.; Shin, H. Angew. Chem., Intl. Ed. Engl. 1995, 34, 907.
7. (c) Gordon, D. W.; Steele, J. Bioorg. & Med. Chem. Lett. 1995, 5, 47.
8. (a) An, H.; Cummins, L. L.; Griffey, R. H.; Bharadwaj, R.; Haly, B. D.; Fraser, A. S.; Wilson-Lingardo, L.; Risen, L. M.; Wyatt, J. R.; Cook, P. D. J. Am. Chem. Soc. 1997, 119, 3696.
9. (b) Cheng, S.; Comer, D. D.; Williams, J. P.; Myers, P. L.; Boger, D. L. J. Am. Chem. Soc. 1996, 118, 2567.
10. (c) Boger, D. L.; Tarby, C. M.; Myers, P. L.; Caporale, L. H. J. Am. Chem. Soc. 1996, 118, 2109.
11. (d) Shipps, Jr., G. W.; Spitz, U. P.; Rebek, Jr., J. Bioorg. & Med. Chem. 1996, 4, 655.
12. Aryl and benzyl piperazine combinatorial libraries have been prepared via solid-phase chemistry using split/pool techniques. See: Dankwardt, S. M.; Newman, S. R.; Krstenansky, J. L. Tetrahedron Lett. 1995, 36, 4923.
13. Ostresh, J. M.; Husar, G. M.; Blondelle, S. E.; Dorner, B.; Weber, P. A.; Houghten, R. A. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 11138.
14. +) (322, 336, 340, 347, 367, 380, 390).
15. (a) Kawasaki, A. M. unpublished results.
16. (b) Available from Aldrich Chem. Co., Milwaukee, WI.
17. 3 C: 63.69, H: 9.80, N: 12.38. Found C: 63.29, H: 9.34, N: 12.07.
18. 4), filtered, and was concentrated in vacuo to give Library 6 (117 mg, 77% mass recovery). The library was characterized by ES/MS (365, 375, 385, 402, 412, 439).
19. Houghten, R. A.; Blondelle, S. E.; Dooley, C. T.; Dorner, B.; Eichler, J.; Ostresh, J. M. Mol. Diversity 1996, 2, 41.
20. Kung, P.-P.; Bharadwaj, R.; Fraser, A. S.; Cook, D. R.; Kawasaki, A. M.; Cook, P. D. J. Org. Chem. 1998, in press.