Synthesis Design and Discovery Associate Professor Mick Sherburn

We develop more efficient ways to access compounds of proven medicinal importance and structures of fundamental significance. We do this by designing new domino reaction sequences: spectacular events in which many new bonds are formed in one synthetic operation.

We target synthetically challenging structures and employ unprecedented molecular transformations to access them. The focus of our work is to devise new methods that take the art of chemical synthesis to the next level, rather than simply applying known methods.

We target new molecular recognition and catalysis technologies, using state-of-the-art computational methods (through collaboration) to steer our laboratory work. Overall, we strive to develop practical syntheses of complex molecules.

Current research activities

Total Synthesis of Biologically Important Natural Products

We have developed a novel, efficient and very general way to produce complex polycyclic structures from simple, unsaturated, acyclic precursors using sequences of Diels-Alder reactions. Applications of these processes in total synthesis are being investigated. In 2008 we completed the shortest total synthesis of the natural product triptolide, which shows great potential in medicine due to its myriad biological activities. Lignans like podophyllotoxin have cancer-fighting properties and are used in chemotherapy. An efficient and highly modular approach for the synthesis of lignan natural products has been developed, culminating in several total syntheses, including that of podophyllotoxin. The approach involves a late stage domino radical reaction. Our strategy has several advantages over previous syntheses, the most significant being that it allows a high level of convergency at the end of the synthetic route. Significant progress has also been made towards the natural product viridin, a particularly challenging structure that we have been targeting since 2003.

Fascinating New Designed Structures

Often chemists are inspired by nature's chemical structures to develop syntheses. Sometimes, structures not produced naturally initiate the development of exciting new methods, concepts and principles. Our interest in this area is focused on the dendralenes, one of the four fundamental classes of conjugated hydrocarbon structures. We have devised the first chemical synthesis of this hydrocarbon family, previously believed to be too unstable to prepare. Another important development involves the conversion of the dendralenes into the ivyanes, saturated hydrocarbons with helical structures. These findings have led to a better understanding of the stability and reactivity of organic substances.

Host-Guest Chemistry

Research in this area is concerned with the design and synthesis of our "superbowl" host molecules for molecular recognition, complexation and catalysis. Superbowls are a new class of synthetic hosts with non-collapsible interiors. Major recent advances include the synthesis of new types of superbowl container molecules with different internal dimensions, which can accommodate different "guests". We have also demonstrated for the first time that superbowl molecules selectively encapsulate medicinal agents.

Annual Research Report   (PDF format)

Group members

Academic Staff:
Associate Professor Mick Sherburn (Leader)     |   Alan Payne

PhD Students:
Gomotsang Bojase-Moleta   |   Tanya Bradford   |   Thomas Fallon   |   William Lording   |   Thanh Vinh Nguyen   |   Hiroshi Yoshida

MPhil students:
  Emma Wiadrowski   |   Lucinda Carpinelli   |   Yasemin Sahbaz   |   Mehmet Saglam

Visiting Scholars:
  Andrew Laurence   |   Neil Findlay   |   Nik Osinski

Honours Students:
  Ryan Cox     |   Amelia Ng     |   Cindy Wills

Technical Staff:
Dr Nicholas Kanizaj

Key publications

1. J. Reynolds, A. J. Scott, C. I. Turner, M. S. Sherburn, The Intramolecular Carboxyarylation Approach to Podophyllotoxin. J. Am. Chem. Soc. 2003, 125, 12108-12109.
2. E. S. Barrett, J. L. Irwin, A. J. Edwards, M. S. Sherburn, Superbowl Container Molecules, J. Am. Chem. Soc. 2004, 126, 16747-16749.
3. A. D. Payne, A. C. Willis, M. S. Sherburn, Practical Synthesis and Diels-Alder Chemistry of [4]Dendralene, J. Am. Chem. Soc. 2005, 127, 12188-12189.
4. G. Bojase, A. D. Payne, A. C. Willis, M. S. Sherburn, One-step synthesis and exploratory chemistry of [5]dendralene, Angew. Chem. Int. Ed. 2008, 47, 910-912.
5. M. N. Paddon-Row, L. C. H. Kwan, A. C. Willis, M. S. Sherburn, Enantioselective oxazaborolidinium-catalyzed Diels-Alder reactions without CH•••O hydrogen bonding, Angew. Chem. Int. Ed. 2008, 47, 7013-7017.

>>more publications

private web page: http://rsc.anu.edu.au/~sherburn/ group photos

Associate Professor M S Sherburn Research School of Chemistry, Building 35 Australian National University Canberra ACT 0200 AUSTRALIA Ph: +61 2 6125 4988 Fx: +61 2 6125 8114 E-mail: sherburn@rsc.anu.edu.au