Validating Eaton's Hypothesis: Cubane as a Benzene Bioisostere
Dr. Benjamin A. Chalmers, Hui Xing, Sevan Houston, Dr. Charlotte Clark, Dr. Sussan Ghassabian, Dr. Andy Kuo, Benjamin Cao, Andrea Reitsma, Cody-Ellen P. Murray, Dr. Jeanette E. Stok, Dr. Glen M. Boyle, Carly J. Pierce, Stuart W. Littler, Prof. David A. Winkler, Prof. Paul V. Bernhardt, Dr. Cielo Pasay, Prof. James J. De Voss, Prof. James McCarthy, Prof. Peter G. Parsons, Prof. Gimme H. Walter, Prof. Maree T. Smith, Prof. Helen M. Cooper, Prof. Susan K. Nilsson, Dr. John Tsanaktsidis, Dr. G. Paul Savage and Prof. Craig M. Williams
Article first published online: 5 FEB 2016 | DOI: 10.1002/anie.201510675
Over 25 years ago, Eaton proposed that cubane could act as a benzene bioisostere. This hypothesis has now been confirmed with the synthesis and evaluation of cubane derivatives of five biologically important molecules: Two cubane analogues showed increased bioactivity compared to their benzene counterparts whereas two further analogues were of equal bioactivity.