Research
The principal aim of a synthetic organic chemist is to create new, efficient ways in which molecules can be built. This ability to construct organic molecules is a vital scientific skill, the outcome of which underpins many other disciplines in academia and industry. In the Snape group, we aim to nurture these skills through the development of new synthetic methods to biologically important molecules and structural building blocks and also apply them to the synthesis of natural products.THE SEMI-PINACOL AND RELATED REARRANGEMENTS: Recently, we applied the semi-pinacol rearrangement to the synthesis of highly-functionalised cyclopentenones, and we are continuing to exploit this and other related rearrangements to the synthesis of natural products. For example, work is ongoing in applying the rearrangement to the synthesis of pumiliotoxin C and litseaverticillol A.
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Some recently published work in this area:
- Application of the Semi-Pinacol Rearrangement Towards the Generation of Alkenyl-Substituted Quaternary Carbon Centres: Timothy J. Snape*, Org. Biomol. Chem., 2006, 4, 4144-4148.
- Recent Advances in the Semi-Pinacol Rearrangement of α-Hydroxy Epoxides and Related Compounds: Timothy J. Snape*, Chem. Soc. Rev., 2007, 36, 11, 1823-1842.
THE TRUCE-SMILES REARRANGEMENT: We are also interested in the relatively under utilised Truce-Smiles rearrangement, and hope to be able to develop it into a synthetically useful procedure for the preparation of a whole range of biologically interesting compounds and molecular building blocks.
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Some recently published work in this area:
- A Truce on the Smiles Rearrangement: Revisiting an Old Reaction – The Truce-Smiles Rearrangement: Timothy J. Snape*, Chem. Soc. Rev., 2008, 11, 2452-2458.
- α-Arylation of Aryl-Ketones: Expanding the Scope of the Truce-Smiles Rear-rangement: Timothy J. Snape*, Synlett, 2008, 2689-2691.
MONOAMINE OXIDASE CHEMISTRY: We have developed a template-based mnemonic to allow the prediction of substrates for the enzyme variants of a monoamine oxidase from Aspergillus niger. The model has been exemplified by the asymmetric synthesis of crispine A and a deoxygenated congener.
Some recently published work in this area:
- A Template-Based Mnemonic for Monoamine Oxidase (MAO-N) Catalyzed Reactions and its Application Towards the Chemo-Enzymatic Deracemisation of the Alkaloid (±)-Crispine A: Kevin R. Bailey, Andrew J. Ellis, Renate Reiss, Timothy J. Snape* and Nicholas J. Turner*, Chem. Commun., 2007, 3640-3642. Designated a Chem. Commun. “Hot Article”
Using this initial success as a benchmark, we now hope to elaborate it further towards the asymmetric synthesis of laudanosine and other related alkaloids as well as taking these chiral products on to more complex products containing multiple chiral centres.
ASYMMETRIC SYNTHESIS OF TERTIARY ALCOHOLS: We are interested in developing a generic chemoenzymatic route to chiral tertiary alcohols. The direct synthesis of such molecules is not trivial and the development of a more indirect but flexible approach to them would prove extremely useful, especially since they constitute an important class of compound and are found in numerous natural products and pharmaceuticals.
Synthesis of tertiary alcohol precursors:
Asymmetric synthesis of tertiary alcohols:
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Some recently published work in this area:
- Enzymatic desymmetrisation of (2-hydroxymethyl-oxiranyl)-methanol in organic solvents: Andrea March Cortijos and Timothy J. Snape*, Tetrahedron: Asymmetry, 2008, 19, 15, 1761-1763.
- Towards a chemo-enzymatic method for the asymmetric synthesis of β-amino tertiary alcohols: Andrea March-Cortijos and Timothy J. Snape*, Org. Biomol. Chem., 2009, 7, 5163-5165.
ALKALOID SYNTHESIS: Related to this is the work in the group which is focussed on the chemoenzymatic synthesis of a whole range of pumilotoxins and other alkaloid natural products possessing a tertiary alcohol motif (see top Figure above).
ANTICANCER: We are currently very interested in the anticancer properties of a number of the molecules we make and we have recently embarked upon a research programme looking at the effect certain compounds have on different glioma cell lines.
Some recently published work in this area:
- Effects of Momordica charantia fruit extract with the combination of temozolamide and cisplatin in the treatment of glioma cancer: G. Manoharan, R. W. Lea, T. J. Snape, J. Singh, Proc. Physiol. Soc., 2010, 18, PC22.