A structurally diverse library of polycyclic lactams resulting from systematic placement of proximal functional groups

Angewandte Chemie - International Edition

Volumn 45, Issue 11, 2006, Pages 1722-1726

  Mitchell, Judith M ^a   Shaw, Jared T ^a  

^a BROAD INSTITUTE OF MIT AND HARVARD   (United States)

Author keywords

Asymmetric synthesis; Combinatorial chemistry; Lactams; Synthetic methods

Indexed keywords

ASYMMETRIC SYNTHESIS; COMBINATORIAL CHEMISTRY; LACTAMS; SYNTHETIC METHODS;

ADDITION REACTIONS; ALDEHYDES; AROMATIC COMPOUNDS; CATALYSIS; STEREOCHEMISTRY; SYNTHESIS (CHEMICAL);

NITROGEN COMPOUNDS;

LACTAM;

ARTICLE; CELL GROWTH; CHEMICAL STRUCTURE; CHEMISTRY; COMBINATORIAL CHEMISTRY; DRUG EFFECT; HELA CELL; HUMAN; SACCHAROMYCES CEREVISIAE;

CELL GROWTH PROCESSES; COMBINATORIAL CHEMISTRY TECHNIQUES; HELA CELLS; HUMANS; LACTAMS; MOLECULAR STRUCTURE; SACCHAROMYCES CEREVISIAE;

EID: 33744475697     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/anie.200503341     Document Type: Article

References (61)

1. a) D. S. Tan, Nat. Chem. Biol. 2005, 1, 74-84;
2. b) B. R. Stockwell, Nature 2004, 432, 846-854;
3. c) C. M. Dobson, Nature 2004, 432, 824-828;
4. d) R. L. Strausberg, S. L. Schreiber, Science 2003, 300, 294-295;
5. e) K. S. Lam, M. Lebl, V. Krchnak, Chem. Rev. 1997, 97, 411-448.
6. a) A. Furka, F. Sebestyen, M. Asgedom, G. Dibo, Int. J. Pept. Protein Res. 1991, 37, 487-493;
7. b) R. A. Houghten, C. Pinilla, S. E. Blondelle, J. R. Appel, C. T. Dooley, J. H. Cuervo, Nature 1991, 354, 84-86.
8. a) B. A. Bunin, J. A. Ellman, J. Am. Chem. Soc. 1992, 114, 10997-10998;
9. b) L. A. Thompson, J. A. Ellman, Chem. Rev. 1996, 96, 555-600;
10. c) H. E. Blackwell, L. Perez, R. A. Stavenger, J. A. Tallarico, E. Cope Eatough, M. A. Foley, S. L. Schreiber, Chem. Biol. 2001, 8, 1167-1182;
11. d) P. A. Clemons, A. N. Koehler, B. K. Wagner, T. G. Sprigings, D. R. Spring, R. W. King, S. L. Schreiber, M. A. Foley, Chem. Biol. 2001, 8, 1183-1195;
12. e) D. G. Hall, S. Manku, F. Wang, J. Comb. Chem. 2001, 3, 125-150;
13. f) T. U. Mayer, Trends Cell Biol. 2003, 13, 270-277;
14. g) S. M. Khersonsky, Y.-T. Chang, Comb. Chem. High Throughput Screening 2004, 7, 645-652;
15. h) L. Burdine, T. Kodadek, Chem. Biol. 2004, 11, 593-597;
16. i) D. R. Spring, Chem. Soc. Rev. 2005, 34, 472-482.
17. M. D. Burke, S. L. Schreiber, Angew. Chem. 2004, 116, 48-60;
18. Angew. Chem. Int. Ed. 2004, 43, 46-58.
19. a) E. M. Gordon, M. A. Gallop, D. V. Patel, Acc. Chem. Res. 1996, 29, 144-154;
20. b) M. A. Marx, A.-L. Grillot, C. T. Louer, K. A. Beaver, P. A. Bartlett, J. Am. Chem. Soc. 1997, 119, 6153-6167;
21. c) M. R. Spaller, M. T. Burger, M. Fardis, P. A. Bartlett, Curr. Opin. Chem. Biol. 1997, 1, 47-53.
22. A. Nefzi, J. M. Ostresh, J. Yu, R. A. Houghten, J. Org. Chem. 2004, 69, 3603-3609.
23. a) M. D. Burke, E. M. Berger, S. L. Schreiber, Science 2003, 302, 613-618;
24. b) H. Oguri, S. L. Schreiber, Org. Lett. 2005, 7, 47-50.
25. a) S. Shang, D. S. Tan, Curr. Opin. Chem. Biol. 2005, 9, 248-258;
26. b) S. Fergus, A. Bender, D. R. Spring, Curr. Opin. Chem. Biol. 2005, 9, 304-309;
27. c) R. Breinbauer, I. R. Vetter, H. Waldmann, Angew. Chem. 2002, 114, 3002-3015;
28. Angew. Chem. Int. Ed. 2002, 41, 2878-2890.
29. W. H. B. Sauer, M. K. Schwarz, J. Chem. Inf. Comput. Sci. 2003, 43, 987-1003.
30. Y.-k. Kim, M. A. Arai, T. Arai, J. O. Lamenzo, E. F. Dean III, N. Patterson, P. A. Clemons, S. L. Schreiber, J. Am. Chem. Soc. 2004, 126, 14740-14745.
31. -1 (see the Supporting Information). [12] 2-Aryl oxazolines analogous to 5 occur as siderophore, antitumor natural products, and synthetic inhibitors of lipid-1 biosynthesis; see: a) T. Peterson, J. B. Neilands, Tetrahedron Lett. 1979, 4805-4808;
32. b) M. Tsukamoto, J. Antibiot. 1997, 50, 815-821;
33. and c) M. C. Pirrung, L. N. Tumey, A. L. McClerren, C. R. H. Raetz, J. Am. Chem. Soc. 2003, 125, 1575-1586;
34. quinolones related to 7a and 7b exhibit broad bioactivity and also occur naturally, see: d) I. Jarak, M. Kralj, L. Suman, G. Pavlovic, J. Dogan, I. Piantanida, M. Zinic, K. Pavelic, G. Karminski-Zamola, J. Med. Chem. 2005, 48, 2346-2360;
35. e) B. Baruah, K. Dasu, B. Vaitilingam, A. Vanguri, S. R. Casturi, K. R. Yeleswarapu, Bioorg. Med. Chem. Lett. 2004, 14, 445-448;
36. f) I.-S. Chen, S.-J. Wu, I.-L. Tsai, T.-S. Wu, J. M. Pezzuto, M. C. Lu, H. Chai, N. Suh, C.-M. Teng, J. Nat. Prod. 1994, 57, 1206-1211;
37. 2-benzazepine-3-ones related to 7c and 7d act as μ-opioid antagonists, see: g) I. Van den Eynde, G. Laus, P. W. Schiller, P. Kosson, N. N. Chung, A. W. Lipkowski, D. Tourwe, J. Med. Chem. 2005, 48, 3644-3648.
38. For a recent example of a natural-product-like library, see: a) Z. Gan, P. T. Reddy, S. Quevillon, S. Couve-Bonnaire, P. Arya, Angew. Chem. 2005, 117, 1390-1392;
39. Angew. Chem. Int. Ed. 2005, 44, 1366-1368;
40. for a review, see: b) A. Reayi, P. Arya, Curr. Opin. Chem. Biol. 2005, 9, 240-247.
41. The diisopropylsilyl linker used for this study was developed by Schreiber and co-workers: a) J. A. Tallarico, K. M. Depew, H. E. Pelish, N. J. Westwood, C. W. Lindsley, M. D. Shair, S. L. Schreiber, M. A. Foley, J. Comb. Chem. 2001, 3, 312-318;
42. two variants of this linker were recently described which feature complementary levels of stability: b) G. L. Thomas, M. Ladlow, D. R. Spring, Org. Biomol. Chem. 2004, 2, 1679-1681;
43. c) C. M. DiBlasi, D. E. Macks, D. S. Tan, Org. Lett. 2005, 7, 1777-1780;
44. d) oxazole 1 is prepared in seven steps (see the Supporting Information).
45. a) D. A. Evans, J. M. Janey, N. Magomedov, J. S. Tedrow, Angew. Chem. 2001, 113, 1936-1940;
46. Angew. Chem. Int. Ed. 2001, 40, 1884-1888;
47. b) H. Suga, K. Ikai, T. Ibata, J. Org. Chem. 1999, 64, 7040-7047.
48. a) L. Hunter, M. D. McLeod, C. A. Hutton, Org. Biomol. Chem. 2005, 3, 732-773;
49. b) A. M. Sawayama, H. Tanaka, T. J. Wandless, J. Org. Chem. 2004, 69, 8810-8820.
50. J. M. Janey, PhD thesis, Harvard University (USA), 2003.
51. a) M. J. O'Donnell, F. Delgado, C. Hostettler, R. Schwesinger, Tetrahedron Lett. 1998, 39, 8775-8778;
52. employing amide bases under traditional conditions was unsuccessful; see: b) D. Seebach, J. D. Aebi, M. Gander-Coquoz, R. Naef, Helv. Chim. Acta 1987, 70, 1194-1216;
53. c) S. Jaroch, R. T. Matsuoka, L. E. Overman, Tetrahedron Lett. 1999, 40, 1273-1276;
54. the recently reported phase-transfer conditions provided the desired product in high yield and diastereoselectivity in model solution studies, but failed in the solid phase, see: d) S.-s. Jew, Y.-J. Lee, J. Lee, M. J. Kang, B.-S. Jeong, J.-H. Lee, M.-S. Yoo, M.-J. Kim, S.-h. Choi, J.-M. Ku, H.-g. Park, Angew. Chem. 2004, 116, 2436-2439;
55. Angew. Chem. Int. Ed. 2004, 43, 2382-2385.
56. J. T. Lundquist, J. C. Pelletier, Org. Lett. 2002, 4, 3219-3221.
57. W. L. Scott, J. Alsina, M. J. O'Donnell, J. Comb. Chem. 2003, 5, 684-692.
58. Use of the Irori (Discovery Partners International) Kan system allowed for the exclusion of low-yielding combinations (see the Supporting Information).
59. -1); nine out of 12 compounds sampled were > 80% pure; structures were based on 7a-d (92 compounds), 8 (324), and related structures (113), which will be described in a full account of this study (see the Supporting Information). Use of Irori Kans has proven useful for split/pool solid-phase synthesis of libraries without using chemical encoding; for an example of a library synthesized with X-nanoKans (which hold 1 mg of resin), see: a) K. C. Nicolaou, J. A. Pfefferkorn, H. J. Mitchell, A. J. Roecker, S. Barluenga, G. Q. Cao, R. L. Affleck, J. E. Lillig, J. Am. Chem. Soc. 2000, 122, 9954-9967;
60. previously, 500-600-μm macrobeads were encoded using technology described by Still et al., see: b) M. H. J. Ohlmeyer, R. N. Swanson, L. Dillard, J. C. Reader, G. Asouline, R. Kobayashi, M. Wigler, W. C. Still, Proc. Natl. Acad. Sci. USA 1993, 90, 10922-10926.
61. Several compounds were found to promote the growth of yeast, while a structurally distinct set were cytotoxic to HeLa cells in a dose-dependent manner (see the Supporting Information).