RESEARCH THEMES AND ACTIVITY
Organic Chemistry focusing on Stereoselective Synthesis and Asymmetric Catalysis
The Cox group has a long-standing interest in stereoselective synthesis and in particular, the allylation reaction, which is one of the most valuable C-C bond-forming processes available to the synthetic chemist. We have shown how employing a temporary silicon connection to tether two reacting moieties can dramatically improve / reverse the stereoselectivity of a subsequent intramolecular allylation [Beignet, J., Jervis, P. J., Cox, L. R., (2008), Temporary Silicon Connection Strategies in Intramolecular Allylation of Aldehydes using Allylsilanes. J. Org. Chem., 73: 5462-5475.].
We have also developed intramolecular allylation strategies to synthesise a range of oxygen heterocycles and recently employed our methodology in the first total synthesis of the natural product (-)-aureonitol [Jervis, P. J., Cox, L. R., (2008), Total synthesis of (-)-Aureonitol and 3-epi-Aureonitol. Confirmation of Relative Stereochemistry. J. Org. Chem., 73: 7616-7624.].
Research has more recently shifted away from substrate-controlled reactions to reagent-controlled processes, with a particular focus on the use of chiral Brønsted acids and chiral anions as organocatalysts for the enantioselective allylation of latent electrophiles.
Carbohydrate Chemistry and Chemical Biology
Carbohydrate chemistry has been a research interest in the group for some time. In recent years, we have begun to employ our synthesis skills in the glycolipid arena as part of a highly multidisciplinary project in association with Prof Del Besra (Microbiology, Birmingham) and Prof Vincenzo Cerundolo (Immunology, Oxford).
This productive interdisciplinary research programme focuses on the CD1d molecule, which is a protein that binds glycolipids. Recognition of the resulting protein-lipid complex by receptors on invariant Natural Killer T cells results in an immune response.
We have synthesised a diverse range of novel glycolipids and shown that the structure of the bound glycolipid determines whether the immune response is activated or suppressed. This opens up the possibility of using these small-molecule regulators of the immune response to treat a range of diseases [Jervis, P. J., Cox, L. R., Besra, G. S. (2011) Synthesis of a Versatile Building Block for the Preparation of 6-N-Derivatized α-Galactosyl Ceramides: Rapid Access to Biologically Active Glycolipids. J. Org. Chem., 76: 320-323.].
We are also using labelled analogues to help shed more insight into the mode of action of different glycolipids CD1d agonists [Garcia-Diaz, Y. R., Wojno, J., Cox, L. R., Besra, G. S., (2009), Synthesis of Threitol Ceramide and [14C]Threitol Ceramide, Non-Glycosidic Analogues of the Potent CD1d Antigen α-Galactosyl Ceramide. Tetrahedron: Asymmetry, 20: 747-753.].
Oligoynes and related π-Conjugated Molecules
We have developed a conceptually new approach to oligoyne assembly [for a review: Weller, M. D., Cox, L. R., (2009), A Novel Twist on an Old Theme: β-Halovinylsilanes, A New Elimination Approach to Oligoyne Assembly. C. R. Chimie, 12: 366-377.], which has culminated in our report of the synthesis of a dodecayne [Simpkins, S. M. E., Weller, M. D., Cox, L. R., (2007), β-Chlorovinylsilanes as Masked Alkynes in Oligoyne Assembly: Synthesis of the First Aryl-End-Capped Dodecayne. Chem. Commun., 4035-4037.] This polyyne, consisting of 24 linearly arranged carbon atoms, represents the longest aryl end-capped oligoyne reported to-date and indeed one of the longest oligoynes ever reported. Oligoyne encapsulation strategies are also being developed in order to access even longer π-conjugated frameworks [Simpkins, S. M. E., Kariuki, B. M., Cox, L. R., (2006), Towards the Synthesis of Insulated Oligoynes: a Ring-Closing-Metathesis Approach to Molecular Encapsulation. J. Organomet. Chem., 691:5517-5523.].