Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science

Probing for the Pharmacophore of the Cytotoxic Neoclerodane Salvileucalin B

Nora Heinrich A , Martin G. Banwell A C , Anthony C. Willis A , Ian A. Cade A , Robert J. Capon B and Xiao-Cong Huang B
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A Research School of Chemistry, Institute of Advanced Studies, The Australian National University, Canberra, ACT 0200, Australia.

B Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Qld 4072, Australia.

C Corresponding author. Email:

Australian Journal of Chemistry 65(12) 1679-1686
Submitted: 31 July 2012  Accepted: 31 August 2012   Published: 31 October 2012


The novel [4.3.1]propelladiene 2, which embodies the key structural elements of the pentacyclic core of the cytotoxic neoclerodane salvileucalin B (1), has been prepared using a rhodium-catalysed intramolecular Büchner reaction as the key step. Compound 2 and the readily obtained derivatives 1217 all proved to be essentially inactive when tested against a panel of four human cancer cell lines. Furthermore, not one of these compounds was a P-gp inhibitor.


[1]  Y. Aoyagi, A. Yamazaki, C. Nakatsugawa, H. Fukaya, K. Takeya, S. Kawauchi, H. Izumi, Org. Lett. 2008, 10, 4429.
         | CrossRef | 1:CAS:528:DC%2BD1cXhtFeltL%2FK&md5=5bb9807c659c34ba78fab8c003e27e4eCAS |

[2]  C.-C. Tseng, H. Ding, A. Li, Y. Guan, D. Y.-K. Chen, Org. Lett. 2011, 13, 4410.
         | CrossRef | 1:CAS:528:DC%2BC3MXptVSlu7o%3D&md5=6e014b5becb1899198901360d3d3b4c1CAS |

[3]  R. R. A. Kitson, A. Millemaggi, R. J. K. Taylor, Angew. Chem. Int. Ed. 2009, 48, 9426.
         | CrossRef | 1:CAS:528:DC%2BD1MXhsFars7nE&md5=b16e3b0aaa30e99be4327d58a4a93cb5CAS |

[4]  J. H. Van Drie, Internet Electron. J. Mol. Des. 2007, 6, 271.
         | 1:CAS:528:DC%2BD2sXhtlWksrvM&md5=340c6a70fd0135022e2c7d6df5024472CAS |

[5]  H. Lebel, J.-F. Marcoux, C. Molinaro, A. B. Charette, Chem. Rev. 2003, 103, 977.For a useful review covering this reaction see:
         | CrossRef | 1:CAS:528:DC%2BD3sXislSjt7o%3D&md5=77458b2ef50bfe1918c02eeacfb6f882CAS |

[6]  (a) S. Levin, R. R. Nani, S. E. Reisman, J. Am. Chem. Soc. 2011, 133, 774.
         | CrossRef | 1:CAS:528:DC%2BC3cXhsF2ku7rE&md5=3b505fad335c8139cd2624e4334261f5CAS |
      (b) S. Levin, R. R. Nani, S. E. Reisman, Org. Lett. 2010, 12, 780.Also see:
         | CrossRef |

[7]  G. M. Ksander, R. deJesus, A. Yuan, C. Fink, M. Moskal, E. Carlson, P. Kukkola, N. Bilci, E. Wallace, A. Neubert, D. Feldman, T. Mogelesky, K. Poirier, M. Jeune, R. Steele, J. Wasvery, Z. Stephan, E. Cahill, R. Webb, A. Navarrete, W. Lee, J. Gibson, N. Alexander, H. Sharif, A. Hospattankar, J. Med. Chem. 2001, 44, 4677.
         | CrossRef | 1:CAS:528:DC%2BD3MXosVeisr0%3D&md5=3ea0ceb5a3ea3fd29f3b0b06f670acf6CAS |

[8]  Z. Puterová, A. Andicsová, D. Végh, Tetrahedron 2008, 64, 11262.
         | CrossRef |

[9]  (a) E. D. Goddard-Borger, R. V. Stick, Org. Lett. 2007, 9, 3797.
         | CrossRef | 1:CAS:528:DC%2BD2sXpsVeltro%3D&md5=0b579c983dc6d3ffb9ac0d41bd0fddd5CAS |
      (b) N. Fischer, E. D. Goddard-Borger, R. Greiner, T. M. Klapötke, B. W. Skelton, J. Stierstorfer, J. Org. Chem. 2012, 77, 1760.Also see:
         | CrossRef |

[10]  (a) M. T. Wuesthoff, B. Rickborn, J. Org. Chem. 1968, 33, 1311.For related examples of cyclopropane ring cleavage reactions see:
         | CrossRef | 1:CAS:528:DyaF1cXnslygtw%3D%3D&md5=ee493b8084e7bce12751ef3654991498CAS |
      (b) F. Zutterman, A. Krief, J. Org. Chem. 1983, 48, 1135.
         | CrossRef |

[11]  W. C. Still, M. Kahn, A. Mitra, J. Org. Chem. 1978, 43, 2923.
         | CrossRef | 1:CAS:528:DyaE1cXksF2hu7s%3D&md5=2cd58c5b7c0cfe760018d99626f49c59CAS |

[12]  A. B. Pangborn, M. A. Giardello, R. H. Grubbs, R. K. Rosen, F. J. Timmers, Organometallics 1996, 15, 1518.
         | CrossRef | 1:CAS:528:DyaK28XhtVerur0%3D&md5=f24f158fe747a77c53a3d647a2c34c80CAS |

[13]  Z. Otwinowski, W. Minor, Processing of X-Ray Diffraction Data Collected in Oscillation Mode, in Methods in Enzymology, Volume 276: Macromolecular Crystallography, Part A (Eds C. W. Carter, Jr, R. M. Sweet) 1997, pp. 307–326 (Academic Press: New York, NY).

[14]  A. Altomare, G. Cascarano, C. Giacovazzo, A. Guagliardi, M. C. Burla, G. Polidori, M. Camalli, J. Appl. Cryst. 1994, 27, 435.

[15]  P. W. Betteridge, J. R. Carruthers, R. I. Cooper, K. Prout, D. J. Watkin, J. Appl. Cryst. 2003, 36, 1487.
         | CrossRef | 1:CAS:528:DC%2BD3sXptFekt78%3D&md5=12bbde279219ee325c2485971d730a2bCAS |

[16]  C. J. Henrich, H. R. Bokesch, M. Dean, S. E. Bates, R. W. Robey, E. I. Goncharova, J. A. Wilson, J. B. McMahon, J. Biomol. Screen. 2006, 11, 176.
         | CrossRef | 1:CAS:528:DC%2BD28XjtlCqsbg%3D&md5=12abd29d616fcbca186d646d568408c7CAS |

[17]  C. J. Henrich, R. W. Robey, K. Takada, H. R. Bokesch, S. E. Bates, S. Shukla, S. V. Ambudkar, J. B. McMahon, K. R. Gustafson, ACS Chem. Biol. 2009, 4, 637.
         | CrossRef | 1:CAS:528:DC%2BD1MXotleiurw%3D&md5=e0f4e5fcf59a2840fb5cb19310c1f56fCAS |

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