Coenzyme Chemistry. Thiamin diphosphate (TPP) 1 is a coenzyme used by many enzymes which make and break bonds adjacent to keto groups. We have synthesised deaza analogues (e.g. 2) of intermediates in these reactions. These bind extremely tightly to TPP-dependent enzymes. We aim to make further analogues that are inhibitors of specific enzymes and may thus be of medicinal importance. We also hope to get crystal structures of the analogues bound to their target enzymes which should help to understand how the reactions occur.
Novel Catalysts. Thiazolium salts catalyse a variety of reactions involving making and breaking bonds to a carbonyl carbon (e.g. the benzoin condensation). We have made chiral thiazolium salts (e.g. 3) and have observed asymmetric induction in formation of benzoin. We intend to further develop these catalysts to obtain better levels of asymmetric induction, to probe the mechanism and to introduce binding cavities for increased rate and better selectivities.
Enzyme Chemistry. A key step in tetrapyrrole biosynthesis is the linking of four molecules of the monopyrrole PBG (4) to give a linear tetrapyrrole, catalysed by PBG deaminase. A crystal structure is available and we plan to use this to design and then synthesise analogues of PBG which bind tightly to the enzyme. These will aid understanding of the mechanism and may be of value as antibiotics and/or herbicides.
Biosynthesis of Prodigiosin. (with Prof G. Salmond, Biochemistry) Prodigiosin (see below) is an immunosuppressant with a novel mode of action. We have found the cluster of genes that codes for its biosynthesis in Serratia marcescens and are working on the elucidation of the biosynthetic pathway and the mechanisms of the enzymic reactions involved.
Synthetic Methods for PET. (with Dr F. Aigbirhio, Wolfson Brain Imaging Centre) Positron Emission Tomography (PET) is a technique used for scanning human brain to detect the distribution of compounds of diagnostic interest. It relies on compounds labelled with very short- lived radioisotopes (e.g. 11C or 18F). The whole synthesis of such compounds must not take longer than ~30 mins. The aim of this project is to develop new synthetic methods, using polymer-supported reagents, that will allow such rapid synthesis and isolation of labelled compounds of neuropharmacological importance.
Prodigiosin Biosynthesis: Molec.Microbiol. (2005), 56, 971-89. Chem. Commun. (2008), 1862–1864
Coenzyme Chemistry: FEBS J. (2009), 276, 2905–2916. Org. Biomolec. Chem. (2008), 6, 3561-3572.
Enzyme Chemistry: Org. Biomolec. Chem. (2003), 1, 21-23 and 1443-1446.
Thiazolium Salts: J. Org. Chem. (2001) 66, 5124-5131, J. Chem. Soc., Perkin Trans.1 (1998), 1891.
131. Henning Stöckmann, Andre A. Neves, Henry A. Day, Shaun Stairs, Kevin M. Brindle and Finian J Leeper, “(E,E)-1,5-cyclooctadiene: A small and fast click-chemistry multitalent” Chem. Comm., 2011, 47 (25), 7203-7205.
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130. Elena Cressina, Liuhong Chen, Michael Moulin, Finian J Leeper, Chris Abell and Alison G Smith, “Identification of novel ligands for thiamine pyrophosphate (TPP) riboswitches” Biochem. Soc. Trans., 2011, 39 (2), 652-7.
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129. Manuela Tosin, Yuliya Demydchuk, James S Parascandolo, Covadonga Blasco Per, Finian J Leeper and Peter F Leadlay "In vivo trapping of polyketide intermediates from an assembly line synthase using malonyl carba(dethia)-N-acetyl cysteamines" Chem. Comm., 2011 (12), 3460-2.
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128. Henning Stöckmann, Andre A. Neves, Shaun Stairs, Heather Ireland-Zecchini, Kevin M. Brindle and Finian J. Leeper, “Development and evaluation of new cyclooctynes for cell surface glycan imaging in cancer cells” Chem. Sci., 2011, 2, 932-936.
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127. Andre A. Neves, Henning Stöckmann, Rebecca Harmston, Ellie Pryor, Israt S. Alam, Sarah Fawcett, Heather Ireland-Zecchini, David Y. Lewis, Scott K. Lyons, Finian J. Leeper and Kevin M. Brindle, “Imaging sialylated glycans in a murine tumor in vivo” FASEB J., 2011, in press.
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126. Elena Cressina, Liuhong Chen, Chris Abell, Finian J. Leeper and Alison G. Smith, “Fragment screening against the thiamine pyrophosphate riboswitch thiM” Chem. Sci., 2011, 2, 157-165.
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125. Neil R. Williamson, Suresh Chawrai, Finian J. Leeper and George P. C. Salmond, “Prodiginines and Their Potential Utility as Proapoptotic Anticancer Agents” in Emerging Cancer Therapy: Microbial Approaches and Biotechnological Tools, Chapter 15, pp. 333-366, A. Fialho and A. Chakrabarty (Editors), Wiley 2010.
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124. Liuhong Chen, Elena Cressina, Finian J. Leeper, Alison G. Smith and Chris Abell, “A Fragment-Based Approach to Identifying Ligands for Riboswitches” ACS Chem. Biol., 2010, 5 (4), 355-358.
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123. Xue-yuan Pei, Karl M. Erixon, Ben F. Luisi and Finian J. Leeper “Structural Insights into the Prereaction State of Pyruvate Decarboxylase from Zymomonas mobilis”, Biochemistry, 2010, 49 (8), 1727-1736.
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122. Kwasi Agyei-Owusu and Finian J. Leeper, "Thiamin diphosphate in biological chemistry: analogues of thiamin diphosphate in studies of enzymes and riboswitches", FEBS J., 2009, 276, 2905–2916.
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121. Xue Yuan Pei, Christopher M. Titman, Rene A.W. Frank, Finian J. Leeper and Ben F. Luisi, "Snapshots of Catalysis in the E1 Subunit of the Pyruvate Dehydrogenase Multienzyme Complex", Structure, 2008, 16 (12), 1860-1872.
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120. Karl M. Erixon, Chester L. Dabalos and Finian J. Leeper, "Synthesis and biological evaluation of pyrophosphate mimics of thiamine pyrophosphate based on a triazole scaffold", Org. Biomolec. Chem., 2008, 6, 3561-3572.
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119. Suresh R. Chawrai, Neil R. Williamson, George P. C. Salmond and Finian J. Leeper, "Chemoenzymatic synthesis of prodigiosin analogues – exploring the substrate specificity of PigC", Chem. Commun., 2008, 1862–1864.
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118. Catrine L. Berthold, Dörte Gocke, Martin D. Wood, Finian Leeper, Martina Pohl and Gunter Schneider, "Structure of the branched-chain keto acid decarboxylase (KdcA) from Lactococcus lactis provides insights into the structural basis for the chemoselective and enantioselective carboligation reaction." Acta Cryst., D 2007, 63 (12), 1217–1224.
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117. Neil R. Williamson, Peter C. Fineran, T. Gristwood, Suresh R. Chawrai, Finian J. Leeper and George P. C. Salmond, "Anticancer and Immunosuppressive Properties of Bacterial Prodiginines." Future Microbiology, 2007, 2 (6), 605-618.
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116. Finian J. Leeper and Alison G. Smith, "Editorial: Vitamins and cofactors—chemistry, biochemistry and biology." Nat. Prod. Rep., 2007, 24 (5), 923–926.
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115. Wim Versées, Stijn Spaepen, Martin D. H. Wood, Finian J. Leeper, Jos Vanderleyden and Jan Steyaert, "Molecular mechanism of allosteric substrate activation in a thiamine diphosphate-dependent decarboxylase." J. Biol. Chem., 2008, 282 (48), 35269-35278.
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114. Catrine L. Berthold, Cory G. Toyota, Patricia Moussatche, Martin D. Wood, Finian J. Leeper, Nigel G. J. Richards, Ylva Lindqvist, "Crystallographic snapshots of oxalyl-CoA decarboxylase give new insights into catalysis by non-oxidative ThDP-dependent decarboxylases." Structure, 2007, 15 (7), 853-861.
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113. Karl M. Erixon, Chester L. Dabalos and Finian Leeper, "Inhibition of pyruvate decarboxylase from Z. mobilis by novel analogues of thiamine pyrophosphate: investigating pyrophosphate mimics." Chem. Comm., 2007, 960-962.
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112. René Frank, Finian Leeper and Ben F. Luisi, "Structure, mechanism and catalytic duality of thiamine-dependent enzymes." Cell. Molec. Life Sci., 2007, 64, 892-905.
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111. Neil R. Williamson, Peter C. Fineran, Finian J. Leeper and George P. C. Salmond, "The Regulation and Biosynthesis of Bacterial Prodiginines." Nature Rev. Microbiol., 2006, 4, 887-899.
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110. N. R. Williamson, H. T. Simonsen, A. K. P. Harris, F. J. Leeper and George P. C. Salmond, "Disruption of the copper efflux pump (CopA) of Serratia marcescens ATCC 274 pleiotropically affects copper sensitivity and production of the tripyrrole secondary metabolite, prodigiosin." J. Indust. Microbiol. Biotechnol., 2006, 33 (2), 151-158.
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109. F. J. Leeper, D. Hawksley, S. Mann, C. Perez Melero and M. D. H. Wood, "Studies on Thiamine Diphosphate-dependent Enzymes." Biochem. Soc. Trans., 2005, 33 (4) 772-775.
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108. N. R. Williamson, H. T. Simonsen, R. A. A. Ahmed, G. Goldet, H. Slater, L. Woodley, F. J. Leeper and G. P. C. Salmond, "Biosynthesis of the red antibiotic, prodigiosin, in Serratia: identification of a novel 2-methyl-3-n-amyl-pyrrole (MAP) assembly pathway, definition of the terminal condensing enzyme, and implications for undecylprodigiosin biosynthesis in Streptomyces." Molec. Microbiology, 2005, 56 (4), 971-989.
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107. A. K. P. Harris, N. R. Williamson, H. Slater, A. Cox, S. Abbasi, I. Foulds, H. T. Simonsen, F. J. Leeper and G. P. C. Salmond "The Serratia gene cluster encoding biosynthesis of the red antibiotic, prodigiosin, shows species- and strain-dependent genome context variation." Microbiology,, 2004, 150 (11), 3547-3560.
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106. S. Mann, C. Perez Melero, D. Hawksley and F. J. Leeper "Inhibition of thiamin diphosphate dependent enzymes by 3-deazathiamin diphosphate." Org. Biomolec. Chem.,, 2004, 2 (12), 1732-1741.
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105. C. E. Goodwin and F. J. Leeper "Stereochemistry and Mechanism of the Conversion of 5-Aminolaevulinic Acid into Porphobilinogen Catalysed by Porphobilinogen Synthase." Org. Biomolec. Chem.,, 2003, 1, 1443-1446.
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104. R. Ahmed and F. J. Leeper "A new synthesis of porphobilinogen analogues, inhibitors of hydroxymethylbilane synthase." Org. Biomolec. Chem.,, 2003, 1, 21-23.
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103. M. J. White and F. J. Leeper "Kinetics of the Thiazolium Ion-Catalysed Benzoin Condensation." J. Org. Chem.,, 2001, 66, 5124-5131.
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102. D. Hawksley, D. A. Griffin and F. J. Leeper "Synthesis of 3-Deazathiamine." J. Chem. Soc., Perkin Trans. 1, 2001, 144-148.
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101. K. Ichinose, M. Kodera, F. J. Leeper and A. R. Battersby "Biosynthesis of porphyrins and related macrocycles. Part 51. Proof that a reductive step occurs during the biosynthesis of vitamin B12 by the micro-aerophilic organism, Propionibacterium shermanii" J. Chem. Soc., Perkin Trans. 1,1999, 879-887.
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100. A. R. Battersby and F. J. Leeper "Biosynthesis of B12 in the Aerobic Organism Pseudomonas denitrificans" in Chemistry and Biochemistry of B12 (2nd Edn), R. Banerjee, Editor. 1999, J. Wiley & Sons, New York, p. 507-535.
99. R. L. Knight and F. J. Leeper "Comparison of chiral thiazolium and triazolium salts as asymmetric catalysts for the benzoin condensation" J. Chem. Soc., Perkin Trans. 1,1998, 1891-1893.
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98. P. M. Petersen, C. J. Hawker, N. P. J. Stamford, F. J. Leeper and A. R. Battersby "Biosynthesis of porphyrins and related macrocycles. Part 50. Synthesis of the N-formyl-dihydro analogue of the spiro-intermediate and its interaction with uroporphyrinogen III synthase" J. Chem. Soc., Perkin Trans. 1,1998, 1531-1540.
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97. C. J. Hawker, P. M. Petersen, F. J. Leeper and A. R. Battersby "Biosynthesis of porphyrins and related macrocycles. Part 49. Exploration of synthetic routes to analogues of the spiro-intermediate for porphyrin biosynthesis" J. Chem. Soc., Perkin Trans. 1,1998, 1519-1530.
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96. C. J. Hawker, A. C. Spivey, F. J. Leeper and A. R. Battersby "Biosynthesis of porphyrins and related macrocycles. Part 48. The rearrangement of 2H-pyrroles (pyrrolenines) related to the proposed spiro-intermediate for porphyrin biosynthesis" J. Chem. Soc., Perkin Trans. 1,1998, 1509-1518.
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95. C. J. Hawker, W. M. Stark, A. C. Spivey, P. R. Raithby, F. J. Leeper and A. R. Battersby "Biosynthesis of porphyrins and related macrocycles. Part 47. Synthesis and chemistry of 2H-pyrroles (pyrrolenines) related to the proposed spiro-intermediate for porphyrin biosynthesis" J. Chem. Soc., Perkin Trans. 1,1998, 1493-1508.
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94. A. R. Battersby and F. J. Leeper "Biosynthesis of Vitamin B12" in Biosynthesis: Polyketides and Vitamins, Topics in Current Chemistry,Vol. 195, Springer-Verlag, Heidelberg, 1998, 143-193.
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93. G. Schenk, F. J. Leeper, R. England, P. F. Nixon and R. G. Duggleby "The role of His113 and His114 in pyruvate decarboxylase from Zymomonas mobilis" Eur. J. Biochem.,1997, 248, 63-71.
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92. D. Appleton, A. B. Duguid, S.-K. Lee, Y.-J. Ha, H.-J. Ha and F. J. Leeper "Synthesis of Analogues of 5-Aminolaevulinic Acid and Inhibition of 5-Aminolaevulinic Acid Dehydratase" J. Chem. Soc., Perkin Trans. 1,1998, 89-102.
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91. J. Micklefield, M. Beckmann, R. L. Mackman, M. H. Block, F. J. Leeper and A. R. Battersby "Haem d1: Stereoselective Synthesis of the Macrocycle to Establish its Absolute Configuration as 2R,7R" J. Chem. Soc., Perkin Trans. 1,1997, 2123-2138.
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90. R. L. Mackman, J. Micklefield, M. H. Block, F. J. Leeper and A. R. Battersby "Haem d1: Development of a new coupling procedure leading to the synthesis of isobacteriochlorins" J. Chem. Soc., Perkin Trans. 1,1997, 2111-2122.
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89. C. J. Aucken, F. J. Leeper and A. R. Battersby "Haem d1: Stereoselective synthesis of the reduced form of its parent macrocycle using the original coupling strategy" J. Chem. Soc., Perkin Trans. 1,1997, 2099-2109.
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88. J. J. De Voss, F. J. Leeper and A. R. Battersby "Synthetic studies relevant to biosynthetic research on vitamin B12. Part 12. Modification of the periphery of chlorins and isobacteriochlorins" J. Chem. Soc., Perkin Trans. 1,1997, 1105-1116.
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87. A. U. Gerhard and F. J. Leeper "Synthesis of and Asymmetric Induction by Chiral Polycyclic Thiazolium Salts" Tetrahedron Lett.,1997, 38, 3615-3618. Abstract
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86. R. L. Knight and F. J. Leeper "Synthesis of and Asymmetric Induction by Chiral Bicyclic Thiazolium Salts" Tetrahedron Lett.,1997, 38, 3611-3614. Abstract
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85. C. Gonzalez Bello, C. Abell and F. J. Leeper "Synthesis of tetrahydroquinolines, hexahydrobenzoindolizines and an aryl phosphonate linker for the generation of catalytic antibodies"
J. Chem. Soc., Perkin Trans. 1,1997, 1017-1024.
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84. D. Appleton and F. J. Leeper "Deuterium Isotope Effects on Porphobilinogen Synthesis Catalysed by 5-Aminolaevulinic Acid Dehydratase"
Bioorg. Med. Chem. Lett.,1996, 6, 1191-1194.
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83. F. J. Leeper and M. Rock "Interaction of Analogues of Porphobilinogen with Porphobilinogen Deaminase" J. Chem. Soc., Perkin Trans. 1,1996, 2643-2649. Abstract
82. F. J. Leeper, M. Rock and D. Appleton "Synthesis of Analogues of Porphobilinogen" J. Chem. Soc., Perkin Trans. 1,1996, 2633-2642. Abstract
81. A. C. Spivey, A. Capretta, C. S. Frampton, F. J. Leeper and A. R. Battersby "Biosynthesis of Porphyrins and Related Macrocycles, Part 45. Determination of the Absolute Configuration of the Spirolactam which Inhibits Cosynthetase" J. Chem. Soc., Perkin Trans. 1,1996, 2091-2102. Abstract
80. M. A. Cassidy, N. Crockett, F. J. Leeper and A. R. Battersby "Biosynthesis of Porphyrins and Related Macrocycles, Part 44. Synthetic and Stereochemical Studies on the Proposed Spiro Intermediate for Biosynthesis of the Natural Porphyrins" J. Chem. Soc., Perkin Trans. 1,1996, 2079-2090. Abstract
79. D. Appleton and F. J. Leeper "Mechanism-based Inhibition of 5-Aminolaevulinic Acid Dehydratase from Bacillus subtilis by the 3-Thia Analogue of the Substrate" Chem. Commun.,1996, 303-304. Abstract
78. C. Lawrence, I. M. Bell, C. Abell and F. J. Leeper "Approaches to Antibody-catalysed Cationic Cyclisations: Chemical Studies of Leaving Groups and Cyclisation Modes" Isr. J. Chem.,1996, 36, 161-169.
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77. A. C. Spivey, A. Capretta, C. S. Frampton, F. J. Leeper and A. R. Battersby "Stereochemical Studies on the Proposed Spiro Intermediate for the Biosynthesis of the Natural Porphyrins: Determination by a Novel X-Ray Method of the Absolute Configuration of the Spirolactam which Inhibits Cosynthetase" J. Chem. Soc., Chem. Commun.,1995, 1789-1790.
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76. F. Kiuchi, F. J. Leeper and A. R. Battersby "Biosynthesis of Porphyrins and Related Macrocycles, Part 43. Isolation and Characterisation of Intermediates of Coenzyme B12 Biosynthesis, a Cobyrinic Acid Triamide, the a,c-diamide and their Co-(5'-Deoxy-5'-adenosyl) derivatives, from Propionibacterium shermanii" Chemistry & Biology,1995, 2, 527-532.
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75. F. J. Leeper and S. Howard "Stereocontrolled Syntheses of Polyhydroxy Indolizidines, Including 8a-Epi, 6,8a-Diepi and 1,6-Diepi-castanospermine, Starting from Malic Acid" Tetrahedron Lett.,1995, 36, 2335-2338.
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74. F. J. Leeper, D. H. C. Smith, M. J. Doyle and P. R. Raithby "Bridged Thiazolium Salts as Models for Thiamin: NMR, Crystallographic and Molecular Mechanics Studies" J. Chem. Soc., Perkin Trans. 2,1995, 777-784. Abstract
73. F. J. Leeper and D. H. C. Smith "Bridged Thiazolium Salts as Models for Thiamin: Synthesis and Reactions" J. Chem. Soc., Perkin Trans. 1,1995, 861-873. Abstract
72. Y. Li, A. I. D. Alanine, S. Balachandran, R. A. Vishwakarma, F. J. Leeper and A. R. Battersby "Biosynthesis of Vitamin B12: Mechanistic Studies on the Transfer of a Methyl Group from C-11 to C-12 and Incorporation of 18O" J. Chem. Soc., Chem. Commun.,1994, 2507-2508. Abstract
71. A. I. D. Alanine, Y. Li, N. P. J. Stamford, F. J. Leeper, F. Blanche, L. Debussche and A. R. Battersby "Biosynthesis of Vitamin B12: Studies of the Oxidative and Lactone-forming Steps by 18O-Labelling" J. Chem. Soc., Chem. Commun.,1994, 1649-1650. Abstract
70. F. Blanche, B. Cameron, J. Crouzet, L. Debussche, D. Thibaut, M. Vuilhorgne, F. J. Leeper and A. R. Battersby "Vitamin B12: How the Problem of its Biosynthesis was Solved" Angew. Chem., Int. Ed. Engl.,1995, 34, 383-411. Abstract
69. I. M. Bell, C. Abell and F. J. Leeper "Design and Synthesis of Transition State Analogues for a Cationic Cyclisation" J. Chem. Soc., Perkin Trans.1,1994, 1997-2006. Abstract
68. S. Balachandran, R. A. Vishwakarma, S. M. Monaghan, A. Prelle, N. P. J. Stamford, F. J. Leeper and A. R. Battersby "Biosynthesis of Porphyrins and Related Macrocycles, Part 42. Pulse Labelling Experiments Concerning the Timing of Cobalt Insertion During Vitamin B12 Biosynthesis" J. Chem. Soc., Perkin Trans. 1,1994, 487-491. Abstract
67. K. E. Holt, F. J. Leeper and S. Handa "Synthesis of beta-1-Homonojirimycin and beta-1-Homomannojirimycin using the Enzyme Aldolase" J. Chem. Soc., Perkin Trans.1,1994, 231-234. Abstract
66. A. I. D. Alanine, K. Ichinose, D. Thibaut, L. Debussche, N. P. J. Stamford, F. J. Leeper, F. Blanche and A. R. Battersby "Biosynthesis of Vitamin B12: Use of Specific 13C-Labelling for Structural Studies on Factor IV" J. Chem. Soc., Chem. Commun.,1994, 193-196. Abstract
65. R. A. Vishwakarma, S. Balachandran, A. I. D. Alanine, N. P. J. Stamford, F. Kiuchi, F. J. Leeper and A. R. Battersby "Biosynthesis of Porphyrins and Related Macrocycles. Part 41. Fate of Oxygen Atoms as Precorrin-2 Carrying Eight Labelled Carboxyl Groups (13C18O2H) is Enzymatically Converted into Cobyrinic Acid" J. Chem. Soc., Perkin Trans. 1,1993, 2893-2899. Abstract
64. W. M. Stark, C. J. Hawker, G. J. Hart, A. Philippides, P. M. Petersen, J. D. Lewis, F. J. Leeper and A. R. Battersby "Biosynthesis of Porphyrins and Related Macrocycles, Part 40. Synthesis of a Spiro-Lactam Related to the Proposed Spiro-Intermediate for Porphyrin Biosynthesis: Inhibition of Cosynthetase" J. Chem. Soc., Perkin Trans. 1,1993, 2875-2892. Abstract
63. F. J. Leeper, S. E. Shaw and P. Satish "The Biosynthesis of Cyclizidine: Incorporation of Singly and Doubly Labelled Precursors" Can. J. Chem., 1994, 72, 131-141. Abstract
62. F. J. Leeper "Evidence for a Spirocyclic Intermediate in the Formation of Urogen III by Cosynthetase" in The Biosynthesis of the Tetrapyrrole Pigments, 1994, J. Wiley & Sons, Chichester, p. 111-123. Abstract
61. K. Ichinose, F. J. Leeper and A. R. Battersby "Preparation of [4R-3H]NADH, [4R-3H]NADPH and the Corresponding 4S-Isomers All with Substantial Specific Activities" J. Chem. Soc., Perkin Trans. 1,1993, 1213-1216. Abstract
60. K. Ichinose, M. Kodera, F. J. Leeper and A. R. Battersby "Proof that the Biosynthesis of Vitamin B12 Involves a Reduction Step in an Anaerobic as well as an Aerobic Organism" J. Chem. Soc., Chem. Commun.,1993, 515-517. Abstract
59. J. Micklefield, R. L. Mackman, C. J. Aucken, M. Beckmann, M. H. Block, F. J. Leeper and A. R. Battersby "A Novel Stereoselective Synthesis of the Macrocycle of Heme d1 that Establishes its Absolute Configuration as 2R,7R" J. Chem. Soc., Chem. Commun.,1993, 275-277. Abstract
58. A. R. Battersby, M. H. Block, F. J. Leeper and S. C. Zimmerman "Synthetic Studies Relevant to Biosynthetic Research on Vitamin B12, Part 11. Modification of the East and West Building Blocks and Study of Different Assembly Methods for Synthesis of Isobacteriochlorins" J. Chem. Soc., Perkin Trans. 1,1992, 2189-2195. Abstract
57. A. R. Battersby, M. H. Block, C. J. R. Fookes, P. J. Harrison, G. B. Henderson and F. J. Leeper "Synthetic Studies Relevant to Biosynthetic Research on Vitamin B12, Part 10. Construction of the East and West Building Blocks for Synthesis of Isobacteriochlorins" J. Chem. Soc., Perkin Trans. 1,1992, 2175-2188. Abstract
56. D. Thibaut, F. Kiuchi, L. Debussche, F. Blanche, M. Kodera, F. J. Leeper and A. R. Battersby "Biosynthesis of Vitamin B12: Structural Studies on Precorrin-8x, an Octamethylated Intermediate and the Structure of its Stable Tautomer" J. Chem. Soc., Chem. Commun.,1992, 982-985. Abstract
55. M. Kodera, F. J. Leeper and A. R. Battersby "Biosynthesis of Vitamin B12: The Fate of H-8 as Precorrin-2 is Enzymically Converted into Cobyrinic Acid" J. Chem. Soc., Chem. Commun.,1992, 835-837. Abstract
54. F. J. Leeper and M. Rock "Modified Substrates for Tetrapyrrole Biosynthesis: Analogues of Porphobilinogen Showing Unusual Inhibition of Porphobilinogen Deaminase" J. Chem. Soc., Chem. Commun.,1992, 242-244. Abstract
53. F. Kiuchi, D. Thibaut, L. Debussche, F. J. Leeper, F. Blanche and A. R. Battersby "Biosynthesis of Vitamin B12: Stereochemistry of Transfer of a Hydride Equivalent from NADPH by Precorrin-6x Reductase" J. Chem. Soc., Chem. Commun.,1992, 306-308. Abstract
52. D. Thibaut, F. Kiuchi, L. Debussche, F. J. Leeper, F. Blanche and A. R. Battersby "Biosynthesis of Vitamin B12: Structure of the Ester of a New Biosynthetic Intermediate, Precorrin-6y" J. Chem. Soc., Chem. Commun.,1992, 139-141. Abstract
51. F. Blanche, M. Kodera, M. Couder, F. J. Leeper, D. Thibaut and A. R. Battersby "Biosynthesis of Vitamin B12: Use of a Single 13C Label in the Macrocycle to Confirm C-11 Methylation in Precorrin-6x" J. Chem. Soc., Chem. Commun.,1992, 138-139. Abstract
50. G. W. Weaver, F. J. Leeper, A. R. Battersby, F. Blanche, D. Thibaut and L. Debussche "Biosynthesis of Vitamin B12: the Site of Reduction of Precorrin-6x" J. Chem. Soc., Chem. Commun.,1991, 976-979. Abstract
49. M. A. Cassidy, N. Crockett, F. J. Leeper and A. R. Battersby "Synthetic Studies on the Proposed Spiro Intermediate for Biosynthesis of the Natural Porphyrins: The Stereochemical Probe" J. Chem. Soc., Chem. Commun.,1991, 384-386. Abstract
48. F. J. Leeper "Intermediate Steps in the Biosynthesis of Chlorophylls" in Chlorophylls, H. Scheer, Editor. 1991, CRC Press, Boca Raton, p. 407-431.
47. F. J. Leeper and M. Rock "Synthesis of a Fluorinated Analogue of 5-Aminolaevulinic Acid, a Potential Inhibitor of Porphyrin Biosynthesis" J. Fluor. Chem.,1991, 51, 381-396.
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46. D. Thibaut, L. Debussche, F. Blanche, F. J. Leeper and A. R. Battersby "Biosynthesis of Vitamin B12: The Structure of Precorrin-6x Octamethyl Ester" Proc. Natl. Acad. Sci. USA,1990, 87, 8800-8804.
45. A. R. Battersby and F. J. Leeper "Biosynthesis of the Pigments of Life: Mechanistic Studies on the conversion of Porphobilinogen into Uroporphyrinogen III" Chem. Rev.,1990, 90, 1261-1274.
44. G. W. Weaver, F. Blanche, D. Thibaut, L. Debussche, F. J. Leeper and A. R. Battersby "Biosynthesis of Vitamin B12: Incorporation of 11S-[11-2H]- and 11R-[11-2H]-Porphobilinogen into Sirohydrochlorin and 2,7,20-Trimethylisobacteriochlorin" J. Chem. Soc., Chem. Commun.,1990, 1125-27.
43. F. J. Leeper and D. H. C. Smith "The Effect of Strain on the Catalytic Reactions of Bridged Thiazolium Salts as Models of Thiamin" J. Chem. Soc., Chem. Commun.,1990, 961-963.
42. G. J. Hart, A. D. Miller, U. Beifuss, F. J. Leeper and A. R. Battersby "Biosynthesis of Porphyrins and Related Macrocycles, Part 35. Discovery of a Novel Dipyrrolic Cofactor Essential for the Catalytic Action of Hydroxymethylbilane Synthase (Porphobilinogen Deaminase)" J. Chem. Soc., Perkin Trans. 1,1990, 1979-1993.
41. F. J. Leeper and P. Padmanabhan "Stereospecific Nucleophilic Ring-Opening of a Deuteriated Cyclopropylcarbinol" Tetrahedron Lett.,1989, 30, 5017-5020.
Abstract,
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40. F. J. Leeper and A. R. Battersby "Chirally Tritiated and Deuteriated Compounds in Studies of Biosynthesis" in Synthesis and Applications of Isotopically Labelled Compounds (Proceedings of the Third International Symposium). 1989, Elsevier, p. 41-46.
39. B. Muller, A. N. Collins, M. K. Ellis, W. G. Whittingham, F. J. Leeper and A. R. Battersby "Syntheses Relevant to Vitamin B12 Biosynthesis: The Glutamate Route to (-)-Ring-B Imide and Synthesis of the 2,7,12,20-Tetramethylisobacteriochlorin" J. Chem. Soc., Chem. Commun.,1989, 1119-1122.
38. W. G. Whittingham, M. K. Ellis, P. Guerry, G. B. Henderson, B. Muller, D. A. Taylor, F. J. Leeper and A. R. Battersby "Syntheses Relevant to Vitamin B12 Biosynthesis: The Malate Route to (-)-Ring-B Imide and Synthesis of the 2,7,20-Trimethylisobacteriochlorin" J. Chem. Soc., Chem. Commun.,1989, 1116-1119.
37. A. D. Miller, F. J. Leeper and A. R. Battersby "Biosynthesis of Porphyrins and Related Macrocycles, Part 34. Synthesis and Properties of S-Pyrrolylmethylcysteinyl and e-N-Pyrrolylmethyl-lysyl Peptides" J. Chem. Soc., Perkin Trans. 1,1989, 1943-1956.
36. F. J. Leeper "The Biosynthesis of Porphyrins, Chlorophylls, and Vitamin B12" Natural Products Reports,1989, 6, 171-203.
35. R. D. Brunt, F. J. Leeper, I. Grgurina and A. R. Battersby "Biosynthesis of Vitamin B12: Synthesis of (±)-[5-13C]Faktor-1 Ester: Determination of the Oxidation State of Precorrin-1" J. Chem. Soc., Chem. Commun.,1989, 428-431.
34. P. R. Alefounder, G. J. Hart, A. D. Miller, U. Beifuss, C. Abell, F. J. Leeper and A. R. Battersby "Biosynthesis of the Pigments of Life: Structure and Mode of Action of a Novel Enzymatic Cofactor" Bioorg. Chem.,1989, 17, 121-129.
33. D. M. Arnott, P. J. Harrison, G. B. Henderson, Z.-C. Sheng, F. J. Leeper and A. R. Battersby "Synthetic Studies Relevant to Research on Vitamin B12, Part 9. Synthesis of 20-Methyl and 20-Cyano Isobacteriochlorins" J. Chem. Soc., Perkin Trans. 1,1989, 265-278.
32. F. Blanche, S. Handa, D. Thibaut, C. L. Gibson, F. J. Leeper and A. R. Battersby "Biosynthesis of Vitamin B12: When is the 12b-Methyl Group of the Vitamin Generated by Acetate Decarboxylation?" J. Chem. Soc., Chem. Commun.,1988, 1117-1119.
31. W. M. Stark, M. G. Baker, F. J. Leeper, P. R. Raithby and A. R. Battersby "Biosynthesis of Porphyrins and Related Macrocycles, Part 30. Synthesis of the Macrocycle of the Spiro System Proposed as an Intermediate Generated by Cosynthetase" J. Chem. Soc., Perkin Trans. 1,1988, 1187-1201.
30. A. K. Demetriadou, E. D. Laue, F. J. Leeper and J. Staunton "Isolation and Structure Elucidation of Polivione, a Polyketide Co-metabolite of Citromycetin in Penicillium frequentans" J. Chem. Soc., Perkin Trans. 1,1988, 763-768.
29. F. J. Leeper and D. H. C. Smith "Synthesis and Structure of Bridged Thiazolium Salts" Tetrahedron Lett.,1988, 29, 1325-1328.
Abstract,
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28. G. J. Hart, A. D. Miller, F. J. Leeper and A. R. Battersby "Biosynthesis of the Natural Porphyrins: Proof that Hydroxymethylbilane Synthase (Porphobilinogen Deaminase) uses a Novel Binding Group in its Catalytic Action" J. Chem. Soc., Chem. Commun.,1987, 1762-1764.
27. F. J. Leeper, P. Padmanabhan, G. W. Kirby and G. N. Sheldrake "Biosynthesis of the Indolizidine Alkaloid, Cyclizidine" J. Chem. Soc., Chem. Commun.,1987, 505-506.
26. F. J. Leeper "The Biosynthesis of Porphyrins, Chlorophylls, and Vitamin B12" Natural Products Reports,1987, 4, 441-469.
25. A. R. Battersby, M. G. Baker, H. A. Broadbent, C. J. R. Fookes and F. J. Leeper "Biosynthesis of Porphyrins and Related Macrocycles, Part 29. Synthesis and Chemistry of 2,2-Disubstituted 2H-Pyrroles (Pyrrolenines)" J. Chem. Soc., Perkin Trans. 1,1987, 2027-2048.
24. H. C. Uzar, A. R. Battersby, T. A. Carpenter and F. J. Leeper "Biosynthesis of Porphyrins and Related Macrocycles, Part 28. Development of a Pulse Labelling Method to Determine the C-Methylation Sequence for Vitamin B12" J. Chem. Soc., Perkin Trans. 1,1987, 1689-1696.
23. A. R. Battersby, K. S. Cardwell and F. J. Leeper "Stereochemical Studies on Porphyrin a: Assignment of the Absolute Configuration of a Model Porphyrin by Degradation" J. Chem. Soc., Perkin Trans. 1,1986, 1565-1580.
22. F. J. Leeper "The Biosynthesis of Porphyrins, Chlorophylls, and Vitamin B12" Natural Products Reports,1985, 2, 561-580.
21. W. M. Stark, M. G. Baker, P. R. Raithby, F. J. Leeper and A. R. Battersby "The Spiro-Intermediate Proposed for Biosynthesis of the Natural Porphyrins: Synthesis and Properties of its Macrocycle" J. Chem. Soc., Chem. Commun.,1985, 1294-1296.
20. M. H. Block, S. C. Zimmerman, G. B. Henderson, S. P. D. Turner, S. W. Westwood, F. J. Leeper and A. R. Battersby "Syntheses Relevant to Vitamin B12 Biosynthesis: Synthesis of Sirohydrochlorin and of its Octamethyl Ester" J. Chem. Soc., Chem. Commun.,1985, 1061-1063.
19. A. K. Demetriadou, E. D. Laue, F. J. Leeper and J. Staunton "The Structure of Polivione, a Polyketide Co-metabolite of Citromycetin in Penicillium frequentans" J. Chem. Soc., Chem. Commun.,1985, 762-764.
18. F. J. Leeper "The Biosynthesis of Porphyrins, Chlorophylls, and Vitamin B12" Natural Products Reports,1985, 2, 19-47.
17. D. M. Doddrell, E. D. Laue, F. J. Leeper, J. Staunton, A. Davies, A. B. Davies and G. A. F. Ritchie "Biosynthesis of the Polyether Antibiotic ICI 139603 in Streptomyces longisporoflavus: Investigation of Deuterium Retention after Incorporation of CD313CO2H, 13CD3CO2H, and CH3CD213CO2H using 2H NMR and edited 13C NMR Spectra" J. Chem. Soc., Chem. Commun.,1984, 1302-1304.
16. J. M. Bulsing, E. D. Laue, F. J. Leeper, J. Staunton, D. H. Davies, G. A. F. Ritchie, A. Davies, A. B. Davies and R. P. Mabelis "Biosynthesis of the Polyketide Antibiotic ICI 139603 in Streptomyces longisporoflavus: Assignment of the 13C NMR by Two-Dimensional Methods and Determination of the Origin of the Carbon Atoms" J. Chem. Soc., Chem. Commun.,1984, 1301-1302.
15. F. J. Leeper and J. Staunton "The Biosynthesis of Rubrofusarin, a Polyketide Naphthopyrone from Fusarium culmorum: 13C NMR Assignments and Incorporation of 13C and 2H-Labelled Acetates" J. Chem. Soc., Perkin Trans. 1,1984, 2919-2925.
14. G. J. Hart, F. J. Leeper and A. R. Battersby "Modification of hydroxymethylbilane synthase (porphobilinogen deaminase) by pyridoxal 5-phosphate" Biochem. J.,1984, 222, 93-102.
13. F. J. Leeper and J. Staunton "Biomimetic Syntheses of Polyketide Aromatics from Reaction of an Orsellinate Anion with Pyrones and a Pyrylium Salt" J. Chem. Soc., Perkin Trans. 1,1984, 1053-1059.
12. T. A. Carpenter, G. E. Evans, F. J. Leeper, J. Staunton and M. R. Wilkinson "Reactions of the Carbanion from an Orsellinate Derivative with Electrophiles" J. Chem. Soc., Perkin Trans. 1,1984, 1043-1051.
11. D. A. Griffin, F. J. Leeper and J. Staunton "Biomimetic Syntheses of Polyketide Aromatics from Pyrylium Salts" J. Chem. Soc., Perkin Trans. 1,1984, 1035-1042.
10. F. J. Leeper and P. N. Lowe "The Stereochemistry and Conformation of the Diastereomers of Tetrahydrothiamin" Heterocycles,1983, 20, 65-68.
09. P. N. Lowe, F. J. Leeper and R. N. Perham "Stereoisomers of Tetrahydrothiamin Pyrophosphate, Potent Inhibitors of the Pyruvate Dehydrogenase Multienzyme Complex from Escherichia coli" Biochemistry,1983, 22, 150-157.
08. C. Abell, M. J. Garson, F. J. Leeper and J. Staunton "Biosynthesis of Fungal Metabolites, Alternariol, Mellein, Rubrofusarin and 6-Methylsalicylic Acid from CD3CO2H" J. Chem. Soc., Chem. Commun.,1982, 1011-1013.
07. F. J. Leeper and J. Staunton "Rubrofusarin Biosynthesis in Fusarium culmorum: Incorporation of 13CH313CO2H and CD313CO2H into the Polyketide Naphthalene Nucleus" J. Chem. Soc., Chem. Commun.,1982, 911-912.
06. F. J. Leeper, G. Grue-Sorensen and I. D. Spenser "Biosynthesis of the Quinolizidine Alkaloids. Incorporation of delta-1-Piperideine into Matrine" Canad. J. Chem.,1981, 59, 106-115.
05. T. A. Carpenter, P. J. Jenner, F. J. Leeper and J. Staunton "A Novel Kinetic Deprotonation at a Vinylic Carbon in a Pyrone Ring" J. Chem. Soc., Chem. Commun.,1980, 1227.
04. F. J. Leeper and J. Staunton "Triacetic Lactone and 2,6-Dimethyl-gamma-pyrone as Polyketide Synthons: Syntheses of Torachrysone and Eleutherinol Derivatives" J. Chem. Soc., Chem. Commun.,1979, 206-207.
03. G. E. Evans, F. J. Leeper, J. A. Murphy and J. Staunton "Triacetic Lactone as a Polyketide Synthon: Syntheses of Toralactone and Polyketide-type Anthracene Derivatives" J. Chem. Soc., Chem. Commun.,1979, 205-206.
02. F. J. Leeper and J. Staunton "Biomimetic Syntheses of Heptaketide Metabolites: Alternariol and a Derivative of Rubrofusarin" J. Chem. Soc., Chem. Commun.,1978, 406-407.
01. G. E. Evans, M. J. Garson, D. A. Griffin, F. J. Leeper and J. Staunton "Biomimetic Syntheses of Phenols from Polyketones" in Further Perspectives in Organic Chemistry,1978, Elsevier, Amsterdam, p. 138.
3 . "Biosynthesis: Aromatic Polyketides, Isoprenoids, Alkaloids" (Topics in Current Chemistry, Vol. 209) Ed. F. J. Leeper & J. C. Vederas, Springer-Verlag, Berlin, 2000.
2 . "Biosynthesis: Polyketides and Vitamins" (Topics in Current Chemistry, Vol. 195) Ed. F. J. Leeper & J. C. Vederas, Springer-Verlag, Berlin, 1998.
1 . "Dictionary of Natural Products", Vols 1 to 7 Ed. J. Buckingham, D. C. Ayres, B. W. Bycroft, P. M. Collins, F. D. Gunstone, J. B. Harborne, E. Haslam, R. A. Hill, D. R. Kelly, F. J. Leeper, R. D. H. Murray & I. W. Southon, Chapman & Hall, New York, 1994.