total synthesis and reaction development


Traditionally, the total synthesis of complex natural products is a very challenging task. The research performed in our group is aimed at making total synthesis easier. To accomplish this goal, we work on developing new reactions, applying known reactions in novel ways, and performing organic synthesis using water.   

Project 1

Polycyclic ether construction using the Stetter reaction

Trans-fused polycyclic ethers (often called marine ladder toxins) such as the brevetoxins, ciguatoxins and yessotoxins, have been isolated from organisms responsible for ‘red-tide’ events. Compounds of this class display a varied range of biological effects including anti-fungal, anti-cancer and anti-cystic fibrosis activity. Due to their paucity in nature, however, study into the biological mechanisms of action of these compounds has received less attention than expected. We have invented a concise new organocatalytic route to access molecules with this type of fused-ring array based on the Stetter reaction (Eur. J. Org. Chem., 2011, 6957–6964; Synlett, 2009, 233-236). The project for 2014 will involve the application of this new methodology to the iterative synthesis of the A-E fragment of prymnesin-1.

 

Prymnesin-1

 


Project 2

Organic synthesis “on-water”

For both environmental and safety reasons, water is considered to be the ultimate solvent in which to perform chemical reactions. Despite the fact that most organic compounds are insoluble in water, some organic reactions are actually faster when performed “on water”. We have recently uncovered the explanation for this phenomenon (Chem. Eur. J. 2010, 16, 8972–8974) and have used “on water” catalysis to facilitate total synthesis (Org. Biomol. Chem., 2013, 11, 2452–2459; Green Chem., 2012, 14, 605–609; Chem. Commun. 2010, 46, 8234–8236;Tetrahedron Lett., 2013, 54, 1056–1058). The project for 2014 will be to utilise “on water” catalysis to develop a synthetic route to ansamycin structures (such as geldanamycin).

 

Geldanamycin

 


Project 3

Total synthesis of bromoallene containing natural products

Despite the large number of reactions available to synthetic chemists, there are some molecular architectures that are still incredibly difficult to synthesise. One such class of molecules are the axially chiral bromoallenes. We have recently developed a common synthetic strategy to provide access to any stereoisomer of the core of these molecules (Org. Biomol. Chem. 2011, 9, 2198–2208; Tetrahedron Lett. 2009, 50, 6318–6320). The project for 2014 will be to develop an unprecedented organocatalytic methodology for the total synthesis of these marine natural products including kumausallene and panacene.


Kumausallene

 

For further information, please contact:

Dr Chris McErlean

Room 518A

School of Chemistry

Eastern Avenue

University of Sydney NSW 2006

Phone: +61 2 9351 3970

Email christopher.mcerlean@sydney.edu.au

Website: http://sydney.edu.au/science/chemistry/~mcerlean