Dr Simon Lewis
Profile
Microbial Oxidation of Aromatic Rings
We are interested in the use of bacteria to carry out the dihydroxylation of aromatic rings—a process that would be very difficult to do by conventional chemical means. Of the arene dihydrodiol-producing organisms identified or engineered to date, the majority metabolise substituted arenes 1 to dihydrodiols with the 2,3 substitution pattern 2.
An alternative outcome is the formation of 1,2-substituted dihydrodiols 3.
We are exploiting the microbial oxidation of benzoic acid, to produce 4 - a highly versatile chiral building block for synthesis
Natural Product Total Synthesis
Our group is interested in total synthesis and we have used building block 4 to access natural products such as (+)-zeylenone 5 and (-)-grandifloracin 6. Separately, we also have a programme developing total syntheses of alkaloids of the lycopodium class.
Metal-diene complexes
Bioproduct 4 and its derivatives have a rich organometallic chemistry and we have synthesized and characterized complexes of such dienes as iron carbonyls, cobalt cyclopentadienyls, etc. These complexes in turn allow access to a wider array of organic transformations of the cyclohexadiene, for example access to the opposite enantiomeric series of arene diols.
Carbohydrate Chemistry
Chiron 4 is ideally functionalized for the synthesis of highly oxygenated structures such as carbohydrates. We recently reported access to a new class of hybrid inositol-amino acid structures, which we termed “inosamino acids”.
C-H Activation with base metals
We are interested in using cheap, abundant metals such aluminium and iron to mediate the C-H activation of bulk hydrocarbons. Over 50 years ago, Baddeley reported an unusual “aliphatic Friedel-Crafts” acylation of decalin, which we have exploited to access a range of functionalized decalins. We are also currently probing the mechanism of this intriguing transformation.
Publications
Griffen, J., White, J., Kociok-Kohn, G., Lloyd, M., Wells, A., Arnot, T. and Lewis, S., 2013. New aminocyclitols with quaternary stereocentres via acylnitroso cycloaddition with an ipso,ortho-arene dihydrodiol. Tetrahedron, 69 (29), pp. 5989-5997.
Uosis-Martin, M., Pantos, G. D., Mahon, M. F. and Lewis, S. E., 2013. A model system for the synthesis of complanadine alkaloids by "diverted Kondrat'eva" oxazole-olefin cycloaddition. Journal of Organic Chemistry, 78 (12), pp. 6253-6263.
Ali Khan, M., Mahon, M. F., Lowe, J. P., Stewart, A. J. W. and Lewis, S. E., 2012. Valuable new cyclohexadiene building blocks from cationic η5-iron-carbonyl complexes derived from a microbial arene oxidation product. Chemistry - A European Journal, 18 (42), pp. 13480-13493.
Palframan, M. J., Kociok-Kohn, G. and Lewis, S. E., 2012. Photooxygenation of a microbial arene oxidation product and regioselective Kornblum-DeLamare rearrangement: Total synthesis of zeylenols and zeylenones. Chemistry - A European Journal, 18 (15), pp. 4766-4774.
Van Der Waals, D., Pugh, T., Khan, M. A., Stewart, A. J. W., Johnson, A. L. and Lewis, S. E., 2011. A cobalt complex of a microbial arene oxidation product. Chemistry Central Journal, 5 (1), 80.
Andersson, D. A., Gentry, C., Alenmyr, L., Killander, D., Lewis, S. E., Andersson, A., Bucher, B., Galzi, J. L., Sterner, O., Bevan, S., Hogestatt, E. D. and Zygmunt, P. M., 2011. TRPA1 mediates spinal antinociception induced by acetaminophen and the cannabinoid Δ9-tetrahydrocannabiorcol. Nature Communications, 2, 551.
Uosis-Martin, M., Mahon, M. F., Yevglevskis, M. and Lewis, S. E., 2011. Concise Synthesis of 1,4a-Bifunctionalised Decalin Building Blocks by C-H Activation of Decalin. Synlett, 2011 (15), pp. 2211-2213.
Palframan, M. J., Kociok-Kohn, G. and Lewis, S. E., 2011. Total synthesis of (+)-grandifloracin by iron complexation of a microbial arene oxidation product. Organic Letters, 13 (12), pp. 3150-3153.
Griffen, J. A., Le Coz, A. M., Kociok-Kohn, G., Ali Khan, M., Stewart, A. J. W. and Lewis, S. E., 2011. Expanding the chiral pool: oxidation of meta-bromobenzoic acid by R. eutrophus B9 allows access to new reaction manifolds. Organic and Biomolecular Chemistry, 9 (10), pp. 3920-3928.
Pilgrim, S., Kociok-Kohn, G., Lloyd, M. D. and Lewis, S. E., 2011. "Inosaminoacids": novel inositol-amino acid hybrid structures accessed by microbial arene oxidation. Chemical Communications, 47 (16), pp. 4799-4801.
Ali Khan, M., Lowe, J. P., Johnson, A. L., Stewart, A. J. W. and Lewis, S. E., 2011. Accessing the antipodal series in microbial arene oxidation: a novel diene rearrangement induced by tricarbonyliron(0) complexation. Chemical Communications, 47 (1), pp. 215-217.
Baker, T. and Lewis, S. E., 2010. Bifunctional silyl triflates in synthesis. Part 1: Synthesis and characterization of novel alkane-,-diyl-bis(silyl triflates). Synthetic Communications, 40 (18), pp. 2747-2752.
Craig, D., Gore, S. J., Lansdell, M. I., Lewis, S., Mayweg, A. V. W. and White, A. J. P., 2010. Transannular, decarboxylative Claisen rearrangement reactions for the synthesis of sulfur-substituted vinylcyclopropanes. Chemical Communications, 46 (27), pp. 4991-4993.
Lewis, S. E., 2010. Synthetic methods: part (ii) oxidation and reduction methods. Annual Reports - Section B Organic Chemistry, 106, pp. 34-75.
Kociok-Kohn, G. and Lewis, S., 2010. Crystallographic rationalization of the reactivity and spectroscopic properties of (2R)-S-(2,5-dihydroxyphenyl)cysteine. Acta Crystallographica Section C-Crystal Structure Communications, 66 (4), O187-O189.
Ali Khan, M., Mahon, M. F., Stewart, A. J. W. and Lewis, S. E., 2010. Iron(0) tricarbonyl complexes of microbially derived cyclohexadiene ligands containing quaternary stereocenters. Organometallics, 29 (1), pp. 199-204.
Lewis, S. E., 2009. Synthetic methods : Part (ii) oxidation and reduction methods. Annual Reports - Section B Organic Chemistry, 105, pp. 35-74.
