Research Guides

Department of Chemistry University of Oxford

Professor Ed Anderson

Our research encompasses all aspects of synthetic organic chemistry, with a particular focus on the total synthesis of biologically active molecules, and the development of new reactions including cascade processes. We aim to use the exciting and challenging chemical structures displayed by bioactive natural products to inspire the development of new reactions. High importance is placed on both reaction generality (to demonstrate wide substrate scope), and on finding additional uses of the reaction products (to increase method utility). Within the theme of reaction development, we have particular interests in the use of metal-mediated reactions to rapidly construct complex functional molecules, and in new applications of organosilicon chemistry.

1. Total Synthesis
Natural products have long provided inspiration for much of the research in the group, as well as offering targets of biological interest. We regard natural products not only as valuable commodities for medicinal chemistry applications, and of course as challenging synthetic targets, but also as “catalysts” for the development of new synthetic methods. In designing a route towards a selected molecule, we seek to develop and optimize new methodology, which extends beyond the specific setting of the natural product towards more generalised reactivity. In this way, total synthesis not only represents a goal in its own right, but also a vehicle for the development of new chemistry.
 
We have recently completed two total syntheses of the natural product rubriflordilactone A (1), a natural product from a large family of terpenoids possessing anti-HIV activity. We employed two different strategies to converge on a late stage synthetic intermdiate, both of which use transition metal catalysis in the key ring-forming transformations – specifically, palladium-catalyzed cyclization of bromoenediyne 2, or cobalt-catalyzed cyclotrimerization of triyne 3. After arylsilane oxidation benzylic deoxygenation, the common pentacyclic product is just four steps from the completion of the synthesis. We are now applying these synthetic principles to other members of this interesting natural product family.
 
 
2. Catalysis / New synthetic methods
We are broadly interested in transition metal catalysis, in particular using palladium, rhodium, and ruthenium catalysts to effect useful and stereoselective transformations. Recent work on ynamides typifies this chemistry: palladium-catalyzed cycloisomerization of enynamides offers an atom-efficient entry to a wide array of azacyclic products. We have uncovered high levels of substrate diastereostereocontrol in these transformations, for example in the formation of single stereoisomers, and have shown that various bicyclic structures can be accessed. We are currently studying aspects of the mechanism of these reactions, including computational analysis with the Paton group in Oxford. 
 
 
3. Mechanistic Studies
Related to our work in new synthetic methods is the development of mechanistic rational for the processes we develop, where we are keen to link experiment with theory. For example, theoretical exploration of the regioselective cyclisation reactions of allenylpalladium intermediates generated from propargylic carbonates revealed a clear correlation between bidentate phosphine bite angle, allenylpalladium bending angle, and the regioselectivity of the cyclisation (collaboration with the Paton group, Oxford).  
 
An ongoing theme of our synthetic research is the application of organic chemistry in virology. Interests in this area range from the synthesis of antiviral molecules (natural and unnatural, for example the Schisandra natural products) to the development of new molecular probes which specifically target intraviral interactions.
 
In this work, we are looking at the inhibition of virus-specific interactions which, by their nature, would represent a process that is difficult for the virus to overcome through mutation. We expect that our work in the field of HIV research might also be extended to other (RNA) viruses. Also we are working on a related project on the synthesis of modified nucleotides that are suitably fuctionalised for use in EPR spectroscopy. 
 
Further information
 
For more detailed information about research and forthcoming positions within the group, please contact me via email.

 

Up to four Part II projects will be offered in 2016-17. Exposure to a wide range of chemistry and an enjoyable working environment is guaranteed!

Part II Students in the group consistently produce high quality, publishable research, and many have gone on to PhD studies following their Part II year. To find out more about current Part II projects in the group please contact me by email.

Cascade polycyclizations in natural product synthesis
R. Ardkhean, D. F. J. Caputo, S. M. Morrow, H. Shi, Y. Xiong and E. A. Anderson, Chem. Soc. Rev., doi: 10.1039/C5CS00105F.

Computational ligand design in enantio- and diastereoselective ynamide [5+2] cycloisomerization
R. N. Straker, Q. Peng, A. Mekareeya, R. S. Paton and E. A. Anderson, Nat. Commun. 20167, 10109.

Combining cycloisomerization with trienamine catalysis: a regiochemically flexible enantio- and diastereoselective synthesis of hexahydroindoles
V. Chintalapudi, E. A. Galvin, R. L. Greenaway and E. A. Anderson, Chem. Commun. 201652, 693.

Total Synthesis of (+)-Rubriflordilactone ATotal Synthesis of (+)-Rubriflordilactone A
S. S. Goh, G. Chaubet, B. Gockel, M.-C. A. Cordonnier, H. Baars, A. W. Phillips and E. A. Anderson, Angew. Chem. Int. Ed., 201554, 12618. 

Ynamide Carbopalladation: A Flexible Route to Mono-, Bi- and Tricyclic Azacycles
C. D. Campbell, R. L. Greenaway, O. T. Holton, P. R. Walker, H. A. Chapman, C. A. Russell, G. Carr, A. L. Thomson and E. A. Anderson, Chem. Eur. J. 2015, 21, 12627.

A robust and modular synthesis of ynamides
S. J. Mansfield, C. D. Campbell, M. W. Jones, and E. A. Anderson, Chem. Commun. 2015, 51, 3316.

Enantioselective Synthesis of the Predominant AB Ring System of the Schisandra Nortriterpenoid Natural Products
B. Gockel, S. S. Goh, E. J. Puttock, H. Baars, G. Chaubet and E. A. Anderson, Org. Lett. 2014, 16, 4480.

Synthesis of Cyclic Alkenylsiloxanes by Semihydrogenation: A Stereospecific Route to (Z)-Alkenyl Polyenes
B. L. Elbert, D. S. W. Lim, H. G. Gudmundsson, J. A. O'Hanlon and E. A. Anderson, Chem. Eur. J. 2014, 20, 8594.

Carbopalladation of bromoene-alkynylsilanes: mechanistic insights and synthesis of fused-ring bicyclic silanes and phenols
M.-C. A. Cordonnier, S. B. J. Kan, B. Gockel, S. S. Goh and E. A. Anderson, Org. Chem. Front. 2014, 1, 661.

Ligand Bite Angle-Dependent Palladium-Catalyzed Cyclization of Propargylic Carbonates to 2-Alkynyl Azacycles or Cyclic Dienamides
D. S. B. Daniels, A. S. Jones, A. L. Thompson, R. S. Paton and E. A. Anderson, Angew. Chem. Int. Ed. 2014, 53, 1915.

Palladium-catalyzed cyclization of bromoenynamides to tricyclic azacycles: synthesis of trikentrin-like frameworks
C. D. Campbell, R. L. Greenaway, O. T. Holton, H. A. Chapman and E. A. Anderson, Chem. Commun 2014, 50, 5187.

Palladium- and Ruthenium-Catalyzed Cycloisomerization of Enynamides and Enynhydrazides: A Rapid Approach to Diverse Azacyclic Frameworks
P. R. Walker, C. D. Campbell, A. Suleman, G. Carr and E. A. Anderson, Angew. Chem. Int. Ed. 2013, 52, 9139.