Skip to content
Publicly Available Published by De Gruyter February 8, 2013

Cycloadditions in heterocycle and alkaloid synthesis

  • Peter Wipf , Zhenglai Fang , Laurent Ferrié , Masafumi Ueda , Maciej A. A. Walczak , Yongzhao Yan and Michael Yang

Intramolecular cycloadditions of bicyclo[1.1.0]butylalkyl-amines represent a rich source of novel heterocyclic scaffolds. As a function of the side chain attached to the amine, formal ene- or [2 + 2] cycloaddition products can be obtained in moderate to high yields. By suitable further functionalizations, a library of 3-azatricyclo[5.1.1.01,5]-nonanes was prepared and interrogated in 450 biological assays. This discovery collection was found to generate high hit rates and yet the individual samples demonstrated sufficient selectivity to fulfill robust lead criteria. These applications of bicyclo[1.1.0]butanes demonstrate that new synthetic chemistry and novel architectures are promising starting points for the generation of high-value discovery libraries.


Conference

International Conference on Organic Synthesis (ICOS-19), International Conference on Organic Synthesis, ICOS, Organic Synthesis, 19th, Melbourne, Australia, 2012-07-01–2012-07-06


References

1 10.1021/jo8001276, A. H. Lipkus, Q. Yuan, K. A. Lucas, S. A. Funk, W. F. Bartelt III, R. J. Schenck, A. J. Trippe. J. Org. Chem.73, 4443 (2008).Search in Google Scholar PubMed

2 10.1021/jm060217p, P. Ertl, S. Jelfs, J. Mühlbacher, A. Schuffenhauer, P. Selzer. J. Med. Chem.49, 4568 (2006).Search in Google Scholar PubMed

3 10.1021/jm801513z, W. R. Pitt, D. M. Parry, B. G. Perry, C. R. Groom. J. Med. Chem.52, 2952 (2009).Search in Google Scholar PubMed

4 10.1021/cb100105c, E. E. Carlson. ACS Chem. Biol.5, 639 (2010).Search in Google Scholar PubMed PubMed Central

5 10.1021/jm801514w, J. Rosén, J. Gottfries, S. Muresan, A. Backlund, T. I. Oprea. J. Med. Chem.52, 1953 (2009).Search in Google Scholar PubMed PubMed Central

6 10.1038/nature03194, J. Clardy, C. Walsh. Nature432, 829 (2004).Search in Google Scholar PubMed

7 10.2533/chimia.2007.355, S. Wetzel, A. Schuffenhauer, S. Roggo, P. Ertl, H. Waldmann. Chimia61, 355 (2007).Search in Google Scholar

8 10.1021/jm200338a, R. A. Ward, J. G. Kettle. J. Med. Chem.54, 4670 (2011).Search in Google Scholar PubMed

9 10.1039/b602413k, J. S. Carey, D. Laffan, C. Thomson, M. T. Williams. Org. Biomol. Chem.4, 2337 (2006).Search in Google Scholar PubMed

10 10.1021/ci600423u, T. Fink, J.-L. Reymond. J. Chem. Inf. Model.47, 342 (2007).Search in Google Scholar PubMed

11 10.1016/j.chembiol.2005.01.011, P. Arya, R. Joseph, Z. Gan, B. Rakic. Chem. Biol.12, 163 (2005).Search in Google Scholar

12 10.1002/anie.200703073, T. E. Nielsen, S. L. Schreiber. Angew. Chem., Int. Ed.47, 48 (2008).Search in Google Scholar

13 10.1021/ci0503558, A. Schuffenhauer, N. Brown, P. Selzer, P. Ertl, E. Jacoby. J. Chem. Inf. Model.46, 525 (2006).Search in Google Scholar

14 10.1039/b504418a, P. Wipf, R. J. Halter. Org. Biomol. Chem.3, 2053 (2005).Search in Google Scholar

15 10.1039/b405431h, P. Wipf, D. J. Minion, R. J. Halter, M. I. Berggren, C. B. Ho, G. G. Chiang, L. Kirkpatrick, R. Abraham, G. Powis. Org. Biomol. Chem.2, 1911 (2004).Search in Google Scholar

16 10.1021/jo005665y, P. Wipf, D. C. Aslan. J. Org. Chem.66, 337 (2001).Search in Google Scholar

17 10.1021/jo015512q, P. Wipf, C. R. Hopkins. J. Org. Chem.66, 3133 (2001).Search in Google Scholar

18 10.1021/jo990089v, P. Wipf, C. R. Hopkins. J. Org. Chem.64, 6881 (1999).Search in Google Scholar

19 10.1021/jo981057v, P. Wipf, T. C. Henninger, S. J. Geib. J. Org. Chem.63, 6088 (1998).Search in Google Scholar

20 10.1016/S0960-894X(98)00026-2, P. Wipf, P. Jeger, Y. Kim. Bioorg. Med. Chem. Lett.8, 351 (1998).Search in Google Scholar

21 10.1016/0040-4039(95)00621-I, P. Wipf, S. Venkatraman, C. P. Miller. Tetrahedron Lett.36, 3639 (1995).Search in Google Scholar

22 10.1039/b815469b, M. A. A. Walczak, B.-K. Shin, P. Wipf, S. Saxena. Org. Biomol. Chem.7, 2363 (2009).Search in Google Scholar PubMed PubMed Central

23 10.1021/ja802906k, M. A. A. Walczak, P. Wipf. J. Am. Chem. Soc.130, 6924 (2008).Search in Google Scholar PubMed PubMed Central

24 10.1016/j.tetlet.2008.07.179, M. Ueda, M. A. A. Walczak, P. Wipf. Tetrahedron Lett.49, 5986 (2008).Search in Google Scholar PubMed PubMed Central

25 10.1002/anie.200600723, P. Wipf, M. A. A. Walczak. Angew. Chem., Int. Ed.45, 4172 (2006).Search in Google Scholar PubMed

26 10.1021/ja038623a, P. Wipf, C. R. J. Stephenson, K. Okumura. J. Am. Chem. Soc.125, 14694 (2003).Search in Google Scholar PubMed

27 10.1016/j.bmcl.2011.12.127, G. Liang, Y. M. Choi-Sledeski, P. Shum, X. Chen, G. B. Poli, V. Kumar, A. Minnich, Q. Wang, J. Tsay, K. Sides, J. Kang, Y. Zhang. Bioorg. Med. Chem. Lett.22, 1606 (2012).Search in Google Scholar PubMed

28 10.1021/jo980190k, J. Weber, U. Haslinger, U. H. Brinker. J. Org. Chem.64, 6085 (1999).Search in Google Scholar

29 S. Hoz. In The Chemistry of the Cyclopropyl Group, Part 2, Z. Rappoport (Ed.), p. 1121, John Wiley, Chichester (1987).Search in Google Scholar

30 10.1021/ja01008a021, P. G. Gassman, K. T. Mansfield. J. Am. Chem. Soc.90, 1524 (1968).Search in Google Scholar

31 10.1021/jm901137j, J. B. Baell, G. A. Holloway. J. Med. Chem.53, 2719 (2010).Search in Google Scholar PubMed

Online erschienen: 2013-2-8
Erschienen im Druck: 2013-2-8

© 2013 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 29.3.2024 from https://www.degruyter.com/document/doi/10.1351/PAC-CON-12-09-03/html
Scroll to top button