Prof Jim Anderson
Research in my laboratory covers a broad portfolio of projects that combine contemporary synthetic organic chemistry methodology with highly adventurous, blue sky research. The basic theme in all of these projects is inventing fundamentally different ways of creating new organic structures in a stereocontrolled and, if applicable, catalytic fashion. This has encompassed the development of new reaction methodology which has been showcased in the synthesis of biologically active natural products, the details of which appear below.
The nitro Mannich reaction for the asymmetric synthesis of 1,2-diamines.
We were the first to characterise and develop the nitro-Mannich reaction for the stereoselective synthesis of 1,2-diamines. The method represents an extremely mild 2 step synthesis of 1,2-diamines from imines and nitro compounds, both of which are readily available.
We have recently been extending the nitro Mannich reaction to produce much more complex β-nitro amines by a tandem conjugate addition/nitro Mannich reaction approach with exquisite control of stereochemistry
The next stage in this research programme is to use the enantiomerically pure 1,2-diamines as building blocks in organic synthesis We are investigating the synthesis of indoline and tetrahydroquinoline skeletons from 1,2-diamines, generated from the nitro Mannich reaction, via palladium catalysed cyclisation onto a pendant aromatic halide or triflate. These will be used in the synthesis of biologically active natural products.
Total synthesis of popolohuanone E.
In total synthesis studies we have been investigating a biomimetic route to the anti cancer natural product popolohuanone E. Development of methodology for the coupling, oxidation and cyclisation of a model compound led to an efficient synthesis of the benzofuran quinine core of popolohuanone E. This protocol has also worked for other analogues we have synthesized for biological testing. We are currently investigating strategies for the first total synthesis of popolohuanone E.
Design of new chiral ligands for asymmetric catalysis.
We have been concentrating on using elements of planar chirality to control chiral induction and have synthesised a range of planar chiral aza-ferrocenes with the capability of chelating to catalytically active metal ions. Ligand 1 controls the asymmetric cycloproponation of styrene to a similar level to that of the leading ligands in the field. While ligand 2 controls the conjugate reduction of an enone.
We are interested to see if the generally larger stereo inducing effect of planar chirality can be harnessed in asymmetric. We are investigating the complexation of new planar chiral ligands with catalytically active metals Rh, Ru and Ti and will investigate catalytic transfer hydrogenation, allylic amination, Diels Alder cyclisations and hydroboration in the near future.
The development of metal oxo chemistry.
In more fundamental work we have been trying to engineer a new synthesis of alkenes involving a carbonyl compound and a metal alkylidene, itself derived from the combination of a metal oxo species with a ketene. We have managed to characterize this process stoichiometrically, but a catalytic variant eludes us at present.
A spin off from this research has been the investigation of some molybdenum oxo-imido aryloxide complexes which are oxo analogues of olefin metathesis catalysts. These complexes are very efficient for the epoxidation of a range of alkenes and are very sensitive to the steric and electronic environment of the alkene allowing regiospecific epoxidation of non conjugated polyenes. We are investigating asymmetric variants of these novel complexes.
Enabling fundamental reactions of CO2.
Most starting materials for the synthesis of fine chemicals are ultimately derived from petroleum. Carbon dioxide is also an important natural carbon resource and has many advantages over petroleum; it is non-toxic, nonflamable and abundant. There is also the possibility of recycling CO2 (an environmental pollutant) from industrial emissions. The possibility of using CO2 as the starting material for the synthesis of fine chemicals would be very valuable and is a chemical problem that has yet to be solved. Using our knowledge of metal oxo chemistry we have proposed a new catalytic cycle to make urethanes, which are very valuable to the chemical industry. This represents an extremely atom efficient and green synthesis of these high value compounds.
Modulation of β-lactam resistance in Staphylococcus aureus.
In a collaboration with Prof P. Taylor at the London School of Pharmacy we have been investigating analogues of (-)-epicatechingallate, an extract of green tea as they resensitise MRSA toward common β-lactam antibiotics. We have synthesised more stable analogues and developed a flexible total synthesis to make less hydroxylated B-ring analogues. These have been shown to be as effective if not more so than the natural material. In addition the mechanism of action of these compounds has been studied and we are some way towards understanding their mode of action. Future research will investigate other analogues to conduct a structure activity relationship study. We will synthesise smaller fragments of the molecules to find simpler structures that will fight MRSA.
- A General One-Step Synthesis of β-NitronitrilesAnderson, J.C.; Blake, A.J.; Mills, M.; Ratcliffe, P.D. Org. Lett. 2008, 10, 4141-3
- An Asymmetric Nitro-Mannich Reaction Applicable to Alkyl, Aryl and Heterocyclic IminesAnderson, J.C.; Howell, G.P.; Lawrence, R.M.; Wilson, C. J. Org. Chem. 2005, 70, 5665-70
- Asymmetric Synthesis of 6'-hydroxyarenarol: The Proposed Biosynthetic Precursor to Popolohuanone EMunday, R.H.; Denton, R.M.; Anderson, J.C. J. Org. Chem. 2008, 73, 8033-38
- Enantioselective Functionalisation of the C-2' position of 1,2,3,4,5-Pentamethylaza-ferrocene via Sparteine Mediated Lithiation: Potential New Ligands for Asymmetric CatalysisAnderson, J.C.; Osbourne, J., Woltering, T. Org. Biomol. Chem. 2008, 6, 330-9
- Nucleophilic Reactivity of a d0 Molybdenum Oxo MoietyCross, W.B.; Anderson J.C.; Wilson, C.S. J. Chem. Soc. Dalton Trans. 2009, 1201-5
- Molybdenum Oxo-Imido Aryloxide Complexes: Oxo Analogues of Olefin Metathesis CatalystsCross, W.B.; Anderson, J.C.; Wilson, C.S.; Blake, A.J. Inorg. Chem. 2006, 45, 4556-61
- Asymmetric Total Synthesis of B-ring Modified (-)-Epicatechin Gallate Analogues and their Modulation of β-Lactam Resistance in Staphylococcus aureusAnderson, J.C.; Headley, C.; Stapleton, P.D.; Taylor, P.W. Tetrahedron 2005, 61, 7703-11.