Versatile approach to encoding combinatorial organic syntheses using chemically robust secondary amine tags

Journal of Medicinal Chemistry

Volumn 39, Issue 8, 1996, Pages 1601-1608

  Ni, Zhi Jie ^a   Maclean, Derek ^a   Holmes, Christopher P ^a   Murphy, Martin M ^a   Ruhland, Beatrice ^a   Jacobs, Jeffrey W ^a   Gordon, Eric M ^a   Gallop, Mark A ^a  

^a AFFYMAX RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 THIAZOLIDINONE DERIVATIVE; AMINE; BETA LACTAM ANTIBIOTIC; PYRROLIDINE DERIVATIVE; RESIN;

ARTICLE; DRUG SYNTHESIS; HYDROLYSIS; REVERSED PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY;

ANTI-BACTERIAL AGENTS; LACTAMS; PYRROLIDINES; THIAZOLES;

EID: 0029873825     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm960043j     Document Type: Article

References (26)

1. (a) Gallop, M. A.; Barrett, R. W.; Dower, W. J.; Fodor, S. P. A.; Gordon, E. M. Applications of Combinatorial Technologies to Drug Discovery. 1. Background and Peptide Combinatorial Libraries. J. Med. Chem. 1994, 37, 1233-1251.
2. (b) Gordon, E. M.; Barrett, R. W.; Dower, W. J.; Fodor, S. P. A.; Gallop, M. A. Applications of Combinatorial Technologies to Drug Discovery. 2. Combinatorial Organic Synthesis, Library Screening Strategies, and Future Directions. J. Med. Chem. 1994, 37, 1385-1401.
3. (c) Terrett, N. K.; Gardner, M.; Gordon, D. W.; Kobylecki, R. J.; Steele, J. Combinatorial Synthesis - The Design of Compound Libraries and their Application to Drug Discovery. Tetrahedron 1995, 51, 8135-8173.
4. (d) Gordon, E. M.; Gallop, M. A.; Patel, D. V. Strategy and Tactics in Combinatorial Organic Synthesis. Applications to Drug Discovery. Acc. Chem. Res. 1996, 29, 144-154.
5. Furka, A.; Sebestyen, F.; Asgedom, M.; Dibo, G. General Method for Rapid Synthesis of Multicomponent Peptide Mixtures. Int. J. Pept. Protein Res. 1991, 37, 487-493.
6. Dower, W. J.; Barrett, R. W.; Gallop, M. A.; Needels, M. C. Method of Synthesizing Diverse Collection of Oligomers. PCT Application WO 93/06121.
7. Brenner, S.; Lerner, R. A. Encoded Combinatorial Chemistry. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 5181-5183.
8. For encoded synthesis using oligonucleotide tags, see: (a) Needels, M. C.; Jones, D. G.; Tate, E. H.; Heinkel, G. L.; Kochersperger, L. M.; Dower, W. J.; Barrett, R. W.; Gallop, M. A. Generation and Screening of an Oligonucleotide-Encoded Synthetic Peptide Library. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 10700-10704. (b) Nielsen, J.; Brenner, S.; Janda, K. D. Synthetic Methods for the Implementation of Encoded Combinatorial Chemistry. J. Am. Chem. Soc. 1993, 115, 9812-9813.
9. For encoded synthesis using oligonucleotide tags, see: (a) Needels, M. C.; Jones, D. G.; Tate, E. H.; Heinkel, G. L.; Kochersperger, L. M.; Dower, W. J.; Barrett, R. W.; Gallop, M. A. Generation and Screening of an Oligonucleotide-Encoded Synthetic Peptide Library. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 10700-10704. (b) Nielsen, J.; Brenner, S.; Janda, K. D. Synthetic Methods for the Implementation of Encoded Combinatorial Chemistry. J. Am. Chem. Soc. 1993, 115, 9812-9813.
10. For encoded synthesis using amino acid tags, see: (a) Kerr, J. M.; Banville, S. C.; Zuckermann, R. N. Encoded Combinatorial Peptide Libraries Containing Non-Natural Amino Acids. J. Am. Chem. Soc. 1993, 115, 2529-2531. (b) Nikolaiev, V.; Stierandova, A.; Krchnak, V ; Seligrnann, B.; Lam, K. S.; Salmon, S. E.; Lebl, M. Peptide-Encoding for Structure Determination of Nonsequenceable Polymers Within Libraries Synthesized and Tested on Solid-Phase Supports. Pept. Res. 1993, 6, 161-170. (c) Krchnak, V.; Weichsel, A. S.; Cabel, D.; Lebl, M. Linear Presentation of Variable Side-Chain Spacing in a Highly Diverse Combinatorial Library. Pept. Res. 1995, 8, 198-205.
11. For encoded synthesis using amino acid tags, see: (a) Kerr, J. M.; Banville, S. C.; Zuckermann, R. N. Encoded Combinatorial Peptide Libraries Containing Non-Natural Amino Acids. J. Am. Chem. Soc. 1993, 115, 2529-2531. (b) Nikolaiev, V.; Stierandova, A.; Krchnak, V ; Seligrnann, B.; Lam, K. S.; Salmon, S. E.; Lebl, M. Peptide-Encoding for Structure Determination of Nonsequenceable Polymers Within Libraries Synthesized and Tested on Solid-Phase Supports. Pept. Res. 1993, 6, 161-170. (c) Krchnak, V.; Weichsel, A. S.; Cabel, D.; Lebl, M. Linear Presentation of Variable Side-Chain Spacing in a Highly Diverse Combinatorial Library. Pept. Res. 1995, 8, 198-205.
12. For encoded synthesis using amino acid tags, see: (a) Kerr, J. M.; Banville, S. C.; Zuckermann, R. N. Encoded Combinatorial Peptide Libraries Containing Non-Natural Amino Acids. J. Am. Chem. Soc. 1993, 115, 2529-2531. (b) Nikolaiev, V.; Stierandova, A.; Krchnak, V ; Seligrnann, B.; Lam, K. S.; Salmon, S. E.; Lebl, M. Peptide-Encoding for Structure Determination of Nonsequenceable Polymers Within Libraries Synthesized and Tested on Solid-Phase Supports. Pept. Res. 1993, 6, 161-170. (c) Krchnak, V.; Weichsel, A. S.; Cabel, D.; Lebl, M. Linear Presentation of Variable Side-Chain Spacing in a Highly Diverse Combinatorial Library. Pept. Res. 1995, 8, 198-205.
13. For encoded synthesis using haloaromatic tags, see: (a) Ohlmeyer, M. H. J.; Swanson, R. N.; Dillard, L. W.; Reader, J. C.; Asouline, G.; Kobayashi, R.; Wigler, M.; Still, W. C. Complex Synthetic Chemical Libraries Indexed with Molecular Tags. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 10922-10926. (b) Nestler, H. P.; Bartlett, P. A.; Still, W. C. A General Method for Molecular Tagging of Encoded Combinatorial Chemistry Libraries. J Org. Chem. 1994, 59, 4723-4724.
14. For encoded synthesis using haloaromatic tags, see: (a) Ohlmeyer, M. H. J.; Swanson, R. N.; Dillard, L. W.; Reader, J. C.; Asouline, G.; Kobayashi, R.; Wigler, M.; Still, W. C. Complex Synthetic Chemical Libraries Indexed with Molecular Tags. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 10922-10926. (b) Nestler, H. P.; Bartlett, P. A.; Still, W. C. A General Method for Molecular Tagging of Encoded Combinatorial Chemistry Libraries. J Org. Chem. 1994, 59, 4723-4724.
15. As an alternative to molecularly based tags, two recent reports describe the use of radiofrequency encodable microchips as information storage media for combinatorial synthesis, i.e.: (a) Moran, E. J.; Sarshar, S.; Cargil, J. F.; Shahbaz, M. M.; Lio, A.; Mjalli, A. M M.; Armstrong, R. W. Radio Frequency Tag Encoded Combinatorial Library Method for the Discovery of Tripeptide-Substituted Cinnamic Acid Inhibitors of the Protein Tyrosine Phosphatase PTP1B. J. Am. Chem. Soc. 1995, 117, 10787-10788. (b) Nicolaou, K. C.; Xiao, X. -Y.; Parandoosh, Z.; Senyei, A.; Nova, M. P. Radiofrequency Encoded Combinatorial Chemistry. Angew. Chem., Int. Ed. Engl. 1995, 34, 2289-2291.
16. As an alternative to molecularly based tags, two recent reports describe the use of radiofrequency encodable microchips as information storage media for combinatorial synthesis, i.e.: (a) Moran, E. J.; Sarshar, S.; Cargil, J. F.; Shahbaz, M. M.; Lio, A.; Mjalli, A. M M.; Armstrong, R. W. Radio Frequency Tag Encoded Combinatorial Library Method for the Discovery of Tripeptide-Substituted Cinnamic Acid Inhibitors of the Protein Tyrosine Phosphatase PTP1B. J. Am. Chem. Soc. 1995, 117, 10787-10788. (b) Nicolaou, K. C.; Xiao, X. -Y.; Parandoosh, Z.; Senyei, A.; Nova, M. P. Radiofrequency Encoded Combinatorial Chemistry. Angew. Chem., Int. Ed. Engl. 1995, 34, 2289-2291.
17. In binary encoding, defined mixtures of tags are used to denote the addition of a specific chemical building block in a particular step of ligand synthesis ("binary" refers to the presence or absence of tags in the mixture defining the two states that form the basis of the synthesis code).
18. The 18 amines, listed in order of increasing retention time of their dansyl amides, are N-ethyl-N-butylamine, N-methyl-N-hexylamine, N,N-dibutylamine, N-methyl-N-heptylaimne, N-butyl-N-pentylamine, N,N-dipentylamine: N-butyl-N-heptylamine, N,N-dihexylamine, N-pentyl-N-octylamine, N-propyl-N-decylamine, N-methyl-N-dodecylamine, N,N-bis[(2-ethyl)hexyl]-amine, N,N-dioctylamine, N-butyl-N-dodecylamine, N-pentyl-N-dodecylamine, N-hexyl-N-dodecylamine, N-heptyl-N-dodecylamine, and N,N-didecylamine.
19. The time required to effect this acidic hydrolysis can be reduced to ∼20 min by irradiation of the sealed capillary tube in a domestic microwave oven.
20. Holmes, C. P.; Jones, D. G. Reagents for Combinatorial Organic Synthesis: Development of a New o-Nitrobenzyl Photolabile linker for Solid Phase Synthesis. J. Org. Chem. 1995, 60, 2318-2319.
21. Ruhland, B.; Bhandari, A.; Gordon, E. M.; Gallop, M. A. Solid-Supported Combinatorial Synthesis of Structurally Diverse β-Lactams. J. Am. Chem. Soc. 1996, 118, 253-254.
22. Murphy, M. M.; Schullek, J. R.; Gordon, E. M.; Gallop, M. A. Combinatorial Synthesis of Highly Functionalized Pyrrolidines: Identification of a Potent Angiotensin Converting Enzyme Inhibitor from a Mercaptoacyl Proline Library. J. Am. Chem. Soc. 1995, 117, 7029-7030.
23. Holmes, C. P.; Chinn, J. P.; Look, G. C.; Gordon, E. M.; Gallop, M. A. Strategies for Combinatorial Organic Synthesis: Solution and Polymer-Supported Synthesis of 4-Thiazolidinones and 4-Metathiazanones Derived from Amino Acids. J. Org. Chem. 1995, 60, 7328-7333.
24. The Fmoc protecting group is stable under these conditions; see: Shapiro, G.; Buechler, D. Mild and Rapid Azide-Mediated Palladium Catalyzed Cleavage of Allylester Based Protecting Groups. Tetrahedron Lett. 1994, 35, 5421-5424.
25. By contrast, the rates of aminolysis of resin-bound pentafluorophenyl esters are highly dependent on the steric bulk of the secondary amine nucleophile, and thus, in the second approach, the relative composition of mixtures of tagging amines must be modulated to reflect these kinetic differences.
26. This is a significant limitation with the amino acid-based coding schemes previously described.