Chemistry
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- Chris Ramsden
I was born in Manchester, UK in 1946. I graduated from Sheffield University and received my PhD (W. D. Ollis) in 1970 and DSc in 1990. After post-doctoral work at the University of Texas (M. J. S. Dewar)(1971-3) and University of East Anglia (A. R. Katritzky)(1973-6), I worked in the pharmaceutical industry. I moved to Keele University as Professor of Organic Chemistry in 1992. My research interests are heterocycles and three-centre bonds and applications of their chemistry to biological problems.
Recent research activities have been focussed on the copper-containing enzyme tyrosinase, which is responsible for oxidising phenols in the early stages of the biosynthesis of the pigment melanin. We have investigated aspects of the subtly different mechanism by which tyrosinase oxidises phenols and catechols by designing and synthesising appropriate substrates. More recently we have investigated the long-standing problem of why catechols slowly inhibit tyrosinase and have proposed a reductive-elimination mechanism that leads to irreversible formation of copper(0) in the active site. This work has lead to the investigation of new ortho-quinone chemistry and the formation of new heterocyclic systems.
We are also interested in imidazole derivatives. Simple imidazole derivatives are useful building blocks for more complex natural product analogues. We are particularly interested in the chemistry of aminoimidazoles. Although 5-aminoimidazole ribonucleotide (AIR) is an intermediate in the biosynthesis of purines, the chemistry of simple aminoimidazoles has received little study and we have found them to be useful intermediates for the synthesis of a variety of interesting new molecules. Targets include peptide analogues, oligonucleotide analogues, antiviral agents and anticancer compounds.
We have a long-standing interest in the chemistry of molecules that can only be represented by hypervalent or dipolar structures. Molecules of this type form a very large class of possible structures and they can all be considered to contain three-centre four-electron bonds. This diverse family of structures includes, for example, heterocyclic pyridinium-3-olates and xenon difluoride. Although diverse, because of their similar bonding, molecules containing three-centre four-electron bonds undergo similar general types of reaction and we are interested in exploring applications of these reactions to achieve useful new methodology. Current interests include the use of the cheap and non-toxic (diacetoxyiodo)benzene in organic synthesis and fluorination using xenon difluoride.
Selected Publications
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2010. Mechanistic studies of tyrosinase suicide inactivation. Arkivoc, 260-274.
Full Publications List show
Books
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2010. Handbook of Heterocyclic Chemistry. Elsevier.
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2008. Comprehensive Heterocyclic Chemistry III. Elsevier Science Ltd.
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2007. Science of synthesis Vol 31.
Journal Articles
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2011. F-19 NMR and UV studies of xenon difluoride solution-vessel stability and its relevance to the fluorination of organic substrates. ARKIVOC, 221-U976. link>
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2010. Mechanistic studies of tyrosinase suicide inactivation. Arkivoc, 260-274.
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2010. Studies of the competing rates of catechol oxidation and suicide inactivation of tyrosinase. ARKIVOC, 248-254.
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2008. Preparation of analogues of efaroxan and KU14R as potential imidazoline receptor subtype 3 ligands. JOURNAL OF HETEROCYCLIC CHEMISTRY, vol. 45(3), 887-896. link>
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2008. Studies of para-quinomethane formation during the tyrosinase-catalyzed oxidation of 4-alkylcatechols. ARKIVOC, 258-267. link>
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2007. ortho-Quinone amines and derivatives: the influence of structure on the rates and modes of intramolecular reaction. ARKIVOC, 23-36. link>
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2004. Routes to N-vinyl-nitroimidazoles and N-vinyl-deazapurines. JOURNAL OF HETEROCYCLIC CHEMISTRY, vol. 41(5), 701-705. link>
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2004. Mechanistic studies of catechol generation from secondary quinone amines relevant to indole formation and tyrosinase activation (vol 16, pg 397, 2003). PIGMENT CELL RESEARCH, vol. 17(2), 206. link>
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2004. The influence of electronegativitry on triangular three-centre two-electron bonds: the relative stability of carbonium ions, p-complex chemistry and the 2h? effect. Tetrahedron. doi>
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2003. Formation of para-quinomethanus via 4-aminobutylcatechol oxidation and ortho-quinone tuntomerism. Organic and Biomolecular Chemistry. doi>
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2003. 4-Cyanomethyl-ortho-quinone tuntomerism and the structure of the dienophile in Gates morphine synthesis. Tetrahedron. doi>
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2002. The world's first "pastarimeter": an analogous demonstration of polarimetry using pasta fusilli. Journal of Chemical Education.
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2002. Synthesis of Pyridine-stretched 2'-Deoxynucleosides. Synlett.
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2002. The reaction of xenon difluoride with chloroform. Journal of Fluorine Chemistry. doi>
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2002. Preparation of 4-benzylsulfanyl[1,2,3,5]dithiadiazol-1-ylium chlorides: potential precursors to meso-ionic 1,2,3,5-dithiadiazolium-4-thiolate. Arkivoc, 224-233.
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2002. Influence of Electronegativity on Reactions Involving Triangular Three-Centre, Two-Electron Bonds: The-2h$beta$ Effect. Journal Physical Chemistry A, vol. 106(12), 2777-2780. doi>
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2001. Preparation of Novel 2-(Benzo[b]furan-2-yl)-1H-imidazolines for Photoaffinity labelling and Affinity Isolation of Imidazoline Binding Proteins. J. Heterocyclic Chemistry.
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2001. Preparation of the l\d3\u imidazoline receptor antagonist KU14R and related 2,3-dihydrobenzo[\fIb\fPfuran derivatives. Synthesis, 1546-1550.
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2001. The Noble Hydrocarbons. Chemistry and Industry, 343-344.
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2001. The Oxidative Rearrangement of Furan-2-carboximidamides: Preparation and Properties of 2-Acylaminofurans. J. Chem. Soc., Perkin Transactions 1, 680-689. doi>
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1999. A fresh AIR synthesis. SYNTHESIS-STUTTGART, 985-992. link>
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1998. Tyrosinase kinetics: failure of the auto-activation mechanism of monohydric phenol oxidation by rapid formation of a quinomethane intermediate. Biochem J, vol. 333 ( Pt 3), 685-691. link>
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1998. Incorporation of [F-18]fluoride into xenon difluoride. JOURNAL OF NUCLEAR MEDICINE, vol. 39(5), 231P-232P. link>
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1997. Reaction of hydrazones with methoxy(tosyloxy)iodobenzene (MTIB): Tosylate formation under oxidative conditions. SYNLETT, 27-&. link>
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1996. Tyrosinase-mediated cytotoxicity of 4-substituted phenols: Quantitative structure-thiol-reactivity relationships of the derived o-quinones (vol 10, pg 119, 1995). ANTI-CANCER DRUG DESIGN, vol. 11(8), 637. link>
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1996. Synthesis and characterisation of KU14R a novel antagonist of the pancreatic islet imidazoline binding site. DIABETOLOGIA, vol. 39, 456. link>
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1996. A novel photoaddition of 2-phenylbenzimidazole. JOURNAL OF HETEROCYCLIC CHEMISTRY, vol. 33(4), 1031-1034. link>
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1995. Tyrosinase-mediated cytotoxicity of 4-substituted phenols: quantitative structure-thiol-reactivity relationships of the derived o-quinones. Anticancer Drug Des, vol. 10(2), 119-129. link>
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1995. A SHORT SYNTHESIS AND BIOMIMETIC TRANSFORMATION OF 5-AMINOIMIDAZOLE RIBONUCLEOSIDE (AIRS). SYNLETT, 203-204. link>
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1993. RAPID FLUORODESILYLATION OF ARYLTRIMETHYLSILANES USING XENON DIFLUORIDE - AN EFFICIENT NEW ROUTE TO AROMATIC FLUORIDES. SYNLETT, 753-755. link>
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1993. A STUDY OF 2-AMINOFURANS. JOURNAL OF HETEROCYCLIC CHEMISTRY, vol. 30(1), 113-117. link>
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1989. THE REACTIONS OF C-METHYLHETEROCYCLES WITH THIONYL CHLORIDE .3. THE TRANSFORMATION OF SOME 5-MEMBERED AND 6-MEMBERED HETEROCYCLES. JOURNAL OF HETEROCYCLIC CHEMISTRY, vol. 26(6), 1819-1825. link>
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1985. PLATINUM(II) COMPLEXES OF NITROIMIDAZOLES - SYNTHESIS, CHARACTERIZATION, AND X-RAY CRYSTAL-STRUCTURES OF CIS-DICHLOROBIS[1-(2'-HYDROXYETHYL)-2-HYDROXYMETHYL-5-NITROIMIDAZOLE)PLATINUM(II) AND TRANS-DICHLOROBIS-[1-(2'-HYDROXY-3'-METHOXYPROPYL)-2-NITROIMIDAZOLE]PLATINUM(II)S. JOURNAL OF THE CHEMICAL SOCIETY-DALTON TRANSACTIONS, 795-802. link> doi>
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1979. CYCLIC MESO-IONIC COMPOUNDS .19. REACTION OF 5-ETHOXY-1,2,3,4-TETRAZOLIUM AND 5-ETHOXY-1,2,3,4-THIATRIAZOLIUM TETRAFLUOROBORATES WITH NUCLEOPHILES - PREPARATION OF 1,2,3,4-TETRAZOLIUM AND 1,2,3,4-THIATRIAZOLIUM-5-DICYANOMETHYLIDES. JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 744-746. link> doi>
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1978. HETEROCYCLES IN ORGANIC-SYNTHESIS .12. STUDIES ON SOME 2,4,6-TRIPHENYLPYRIDINIUM BETAINES AND RELATED SPECIES. COLLECTION OF CZECHOSLOVAK CHEMICAL COMMUNICATIONS, vol. 43(8), 2046-2053. link>
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1978. SEMI-EMPIRICAL MO FOR ORGANIC CHEMISTS. CHEMISTRY IN BRITAIN, vol. 14(8), 396-&. link>
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1977. HETEROCYCLES IN ORGANIC-SYNTHESIS .5. CONVERSION OF AMINES INTO IODIDES. SYNTHESIS-STUTTGART, 634-635. link>
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1977. MESOMERIC BETAINE DERIVATIVES OF HETEROPENTALENES. TETRAHEDRON, vol. 33(24), 3203-3232. link>
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1976. HETEROCYCLES IN ORGANIC-SYNTHESIS .2. PYRIDINES AS LEAVING GROUPS IN SYNTHETIC TRANSFORMATIONS - NUCLEOPHILIC DISPLACEMENTS OF AMINO-GROUPS, AND NOVEL PREPARATIONS OF NITRILES AND ISOCYANATES. TETRAHEDRON LETTERS, 2691-2694. link>
Chapters
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2008. Bicyclic 5-6 Systems: Six and Seven Heteroatoms. In Comprehensive Heterocyclic Chemistry III, Vol. 10. Elsevier.
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2007. Arylphosphine oxides. In Science of Synthesis. (vol. Vol. 31b). Georg Thieme Verlag KG.
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2004. Quinone Chemistry and Melanogenesis. In Methods in Enzymology. Sies H and Packer L (Eds.). Elsevier Academic Press, California, USA. doi>
Other
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1999. Studies using hypervalent reagents of Te, I and Xe: A heterocyclic betaine saga. JOURNAL OF HETEROCYCLIC CHEMISTRY (vol. 36, pp. 1573-1579). link>
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1997. Synthesis of new heterocyclic amidines. CHEMICKE LISTY (vol. 91, pp. 655-656). link>
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1995. 5-Aminoimidazole chemistry. KHIMIYA GETEROTSIKLICHESKIKH SOEDINENII (pp. 1323-1331). link>
Year 1
- CHE-10014 - Inventions and Society
- CHE-10002 - Basic Organic Chemistry (Module Leader)
- CHE-10026 - Basic Organic Chemistry for Life Sciences (Module Leader)
- PHA-10010 - Pharmaceutical Chemistry
- PHA-10011 - Drug Discovery and Use
Year 2
- CHE-20005 - Drug Design Based on Biological Targets (Module Leader)
Year 3
- CHE-30006 - Synthesis Kinetics and Mechanism
- CHE-30007 - Medicinal and Biomolecular Chemistry (Module Leader)
- CHE-30008 - Organic Radicals

