1984-1987 BSc (hons) Chemistry Manchester 1987-1988 Research Chemist at ICI Pharmaceuticals (now AstraZeneca). 1988-1989 MSc Organic Synthesis (supervisor, Prof. J.K. Sutherland) Manchester 1989-1991 PhD Organic Synthesis (supervisor, Prof. J.K. Sutherland) Manchester 1991-1995 Postdoctoral research under the guidance of Prof. Sir J.E. Baldwin Oxford 1996-1999 University Lecturer in Organic Chemistry Reading 1999-present University Lecturer in Organic and Biological Chemistry Manchester

Our research interests fall into three main areas: EXPLOITATION OF CHEMICAL PREDISPOSITION IN NATURAL PRODUCT SYNTHESIS We are tackling the syntheses of the sponge derived fatty acid derivatives, manzamenones A and G and the unusual cytotoxic alkaloid, madangamine A, using approaches founded on the principles of predisposed chemistry. NOVEL ANTI-BACTERIAL AND ANTI-FUNGAL AGENTS We are preparing a range of analogues of intermediates on the shikimic acid, tryptophan and histidine biosynthetic pathways, which have been selected as likely competitive inhibitors of various enzymes on the respective pathways. On completion of the synthetic investigations, in vitro studies of the inhibition of purified enzymes by these unnatural substrates will be carried out. NATURALLY OCCURRING ANTI-TUMOUR AGENTS We are interested in preparing a number of naturally occurring anti-tumour agents. In particular, we are investigating the synthesis of varacin, an unusual benzopentathiepin which is 100 times more active than fluorouracil against human colon cancer.

Christou, S.; Ozturk, E.; Pritchard, R.G.; Quayle, P.; Stratford, I.J.; Whitehead, R.C.; Williams, K.F. ‘A synthetic approach to novel carvotacetone and antheminone analogues with anti-tumour activity’. BioOrganic and Medicinal Chemistry Letters. 2013 August; 23: . eScholarID:206093 Lopez-Castejon, G.; Luheshin, N.M.; High, S.; Whitehead, R.C.; Flitsch, S.; Kirov, A.; Prudovsky, I.; Swanton, E.; Brough, D. ‘Deubiquitinases regulate the activity of caspase-1 and IL-1 secretion via assembly of the inflammasome’. Journal of Biological Chemistry. 2013 January; 288: . eScholarID:206099 Craig McKibbin, Alina Mares, Michela Piacenti, Helen Williams, Peristera Roboti, Marjo Puumalainen, Anna C. Callan, Karolina Lesiak-Mieczkowska, Stig Linder, Hanna Harant, Stephen High, Sabine L. Flitsch, Roger C. Whitehead & Eileithyia Swanton. Inhibition of protein translocation at the endoplasmic reticulum promotes activation of the unfolded protein response. The Biochemical Journal. 2012; 442: 639-648. eScholarID:143547 | DOI:10.1042/BJ20111220 Aletrari, MO.; McKibbin, C.; Williams, H.; Pawar, V.; Pietroni, P.; Lord, J.M.; Flitsch, S.L.; Whitehead, R.C.; Swanton, E.; High, S.; Spooner, R.A. Eeyarestatin 1 Interferes with Both Retrograde and Anterograde Intracellular Trafficking Pathways. PLOS ONE. 2011; 6(7): eScholarID:143543 | DOI:10.1371/journal.pone.0022713 Scott KA, Barnes J, Whitehead RC, Stratford IJ, Nolan KA. Inhibitors of NQO1: identification of compounds more potent than dicoumarol without associated off-target effects. Biochem Pharmacol. 2011; 81: 355-363. eScholarID:115721 | DOI:10.1016/j.bcp.2010.10.011 Dunstan, MS; Barnes, J; Humphries, M; Whitehead, RC; Bryce, RA; Leys, D; Stratford, IJ; Nolan, KA. Novel Inhibitors of NRH:Quinone Oxidoreductase 2 (NQO2): Crystal Structures, Biochemical Activity, and Intracellular Effects of Imidazoacridin-6-ones. Journal of medicinal chemistry. 2011; 54(19): 6597-6611. eScholarID:143537 | DOI:10.1021/jm200416e Nolan KA, Scott KA, Barnes J, Doncaster J, Whitehead RC, Stratford IJ. Pharmacological inhibitors of NAD(P)H quinone oxidoreductase, NQO1: Structure/activity relationships and functional activity in tumour cells. BIOCHEMICAL PHARMACOLOGY. 2010; 80(7): 977-981. eScholarID:112742 | DOI:10.1016/j.bcp.2010.06.024 Nolan, K.A.; Humphries, M.P.; Barnes, J.; Doncaster, J.R.; Caraher, M.C.; Tirelli, N.; Bryce, R.A.; Whitehead, R.C.; Stratford, I.J Triazoloacridin-6-ones as novel inhibitors of the quinone oxidoreductases NQO1 and NQO2. Bioorganic and Medicinal Chemistry. 2010; 18(2): 696-706. eScholarID:143534 | DOI:10.1016/j.bmc.2009.11.059 Arthurs, C.L.; Morris, G.A.; Piacenti, M.; Pritchard, R.G.; Stratford, I.J.; Tatic, T.; Whitehead, R.C. Williams, K.F.; Wind, N.S. ‘The synthesis of 2-oxyalkyl-cyclohex-2-enones, related to the bioactive natural products COTC and antheminone A, which possess anti-tumour properties’. Tetrahedron. 2010; 66(46): 9049-9060. eScholarID:112740 | DOI:10.1016/j.tet.2010.08.072

Nolan, K.A.; Humphries, M.P.; Barnes, J.; Doncaster, J.R.; Caraher, M.C.; Tirelli, N.; Bryce, R.A.; Whitehead, R.C.; Stratford, I.J ‘Triazoloacridin-6-ones as novel inhibitors of the quinone oxidoreductases NQO1 and NQO2’. Bioorg. Med. Chem. 2010; 18: 696-706. eScholarID:112725 | DOI:10.1016/j.bmc.2009.11.059