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My PhD and postdoc. research were respectively with Dr. Hamish Sutherland at Imperial College on the development of new peptide coupling agents and with Prof. Alex Nickon at Johns Hopkins University, Baltimore on photosensitised oxidation of steroidal olefins. |
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Key papers: J.Chem. Soc. 1964, 3495; ibid. 4650; J.Am. Chem. Soc. 1965, 30, 1711.
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Further postdoctoral and initial faculty research was, in collaboration with Prof Sir Derek Barton, Nobel Laureate, centred on the structure determination, synthesis and biosynthesis of alkaloids, mainly the Erythrina alkaloids, and the fungal steroids of the yeast Saccharomyces cerevisiae. |
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Key papers: Abh. der Deut. Akad. der Wiss., Berlin 1971, 7; J. Chem. Soc., Perkin Trans. I, 1974, 1326.
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Concurrent with the above work, I initiated studies on models for the biochemical mechanisms of NADH and coenzyme B12 dependent reactions. In particular, the free radical migration of the thiol ester in methylmalonylCoA mutase models was demonstrated and, in collaboration with Dr. Henry Rzepa, an order of migratory aptitude for acyl residues, under radical conditions, predicted. |
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Key papers: J. Chem. Soc., Chem. Commun., 1983, 625; J. Chem. Soc., Perkin Trans. I, 1986, 1139.
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From biosynthesis to biotransformations is a the logical step for an organic chemist and recent bio-work, in collaboration firstly with Professor Doug Ribbons and more recently with Dr. David Leak, has been on the application of dihydroxylase, oxidase and hydratase enzymes, either in whole cells or in purified form, to organic synthesis. |
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Key papers: J. Chem. Soc., Perkin Trans. I, 1995, 2647; Tetrahedron Lett., 1996, 37, 8819
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A long standing collaboration with Professor Vic Pike of the MRC Cyclotron unit at Hammersmith Hospital involves a search for synthetic methods compatible with 18F technology for application in Positron Emission Tomography (PET). This has resulted in the development of fluorodestannylation, fluorodeboronation and fluorodeindiation by caesium fluoroxysulfate and the PET compatible synthesis of fluorosteroids and other pharmaceutical agents. |
Key papers: Tetrahedron, 1992, 48, 8073; J. Chem. Soc., Perkin Trans. I, 1995, 2965.
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In the late seventies, I made a major move into the application of chemo- , regio-, and stereo-specific transition metal mediated reactions to the synthesis of bioactive molecules. This resulted in the discovery of new ortho - directing effects in arenetricarbonylchromium(0) complexes and to the development of new methods for the remote functionalisation of the aromatic ring in these complexes. |
Key papers: Tetrahedron Lett., 1986, 27, 5525; Phil. Trans. R. Soc. Lond., 1988, A 326, 595.
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Heterocyclic arenetricarbonylchromium(0) complexes proved to be an equally fertile area of novel chemistry and the principles of remote functionalisation were applied to the indole complexes and resulted in the development of methods for functionalisation at positions 4-, 6-, and 7- on the indole ring. |
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Key papers: Tetrahedron, 1988, 44, 7325;Tetrahedron, 1989, 45, 5955.
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These techniques were exemplified in the synthesis of chuangxinmycin, a broad spectrum antibiotic found in the chinese soil bacterium Actinoplanes tsinanensis and in the synthesis of the moracins and related resorcinylbenzofuran antifungal agents from the white mulberry tree, Morus alba. |
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Key papers: J. Chem. Soc., Perkin Trans. I, 1992,323; Tetrahedron, 1991, 47, 8621.