Dr John Gardiner

• 5-Year Postdoctoral Research Associate in Synthetic Chemistry/Biocatalysis
  Closing date for applications: 2007-05-24
  
  

BSc (Durham), PhD (Durham).
Postdoctoral research: University of California at Los Angeles (UCLA) 1988-90. Visiting Research Fellow: University of California at Los Angeles (UCLA), 1991 and 1992. Lecturer in Medicinal Chemistry : Aston University 1990-93

Biolgically targeted carbohydrate chemistry:Carbohydrate research interests includes synthesis of isotopically stable-labelled biologically important saccharides which will have applications to study of protein-carbohydrate interactions (in collaboration with structural biologists). This involves a range of organic synthetic methods in the de novo synthesis of various sugars containing versatile labelling patterns, including asymmetric synthesis.

We have also been developing a strategy for synthesis of diverse multivalent carbohydrate ligand mimics, and to explore the behaviour of such systems in biological mimic systems. All projects are characterized by diverse organic synthetic chemistry allied to structural targets for analysis or modelling of biological recognition. We are also collaborating with researchers at the Paterson Institute or Cancer Research on developing synthesis of carbohydrate agents which have high potential as a class of new anticancer drugs.

Heterocyclic chemistry and new DNA/RNA ligands: In the medicinal chemistry/heterocyclic chemistry area, we have developed a novel syntheses of N-alkoxybenzimidazoles 3, and have applied this to generate wide diversity of novel structures, including some dimeric systems. Many bioactive compounds contain benzimidazole type substructures, and our methodology allows access to a very wide range of novel substituted benzimidazole derivatives/scaffolds unavialable by other means. This chemistry should have wide applications. Several of our initial products show promising anti-HIV and anti-cancer activity. Work is now applying this towards DNA/RNA targeted agents.

Biotransformations:We are collaborating with Dr Gill Stephens group in Chemical Engineering on the isolation and optimization of anerobic bacteria for novel asymmetric reductions of both C=C and C=N functionalities. This involves organic synthesis and microbiology. The work has received major BBSRC funding.
This work also is now involved in collaborating with Nigel Scrutton's group in enzymology and Peter Fielden and Nick Goddard's mircofabrication group in CEAS as part of a large programme in biocatalyst development, based in the MIB.

In another area, we have also used parallel enzyme screening to optimize highly efficient desymmetrization (>99% e.e.) in a novel hindered substrate class providing a route to enantiopure polyfunctional building blocks which we will now be exploiting.

Bioactive natural product synthesis: Two potent bioactive natural product have been targets for synthesis: A. the potent anticancer, antiviral and immunosuppressive marine natural product, mycalamide A, 1, (isolated from rare tropical sponges), involving development of new synthetic methodology for an asymmetric synthesis and a chiron-based synthesis of two components of this target. Mycalamides and analogues offer potential as new immunosuppressive drugs and tools for immunobiology.

		B the cardioactive amphibian alkaloid, pumiliotoxin B, 2, and novel analogues. This toxin - isolated from rare, beautifully coloured, Amazonian 'poison arrow' frogs (see left), offers potential as a lead for new drugs for heart failure.

Structures of two new types of terpenoid chiral ligands: The ligand on the right is one of our new multiheteroatom ligands, in this case with 3 different types of heteroatoms.

Dendrimers: We are developing a strategy for the synthesis of novel types of chiral dendrimers, complex multifunctional materials likely to have interesting properties and potential applications in catalysis, selective binding and drug delivery. We are also interested in new ways to evolve dendritic hosts.

Asymmetric synthesis: We are developing synthesis of varieties of new ligands from little explored terpenone scaffolds. A series of diastereomeric homochiral ketoalcohols 4 have been prepared, and now diversified to various new ligand families, including multifunctional, containing up to 5 defined contiguous chiral centres [See structures in figure]. Catalyst screening experiments has provided us some novel ligand lead structures showing high enantioselectivities.

A novel and very efficient kinetic resolution has been developed to optically pure diol 5, and to its (also optically pure) enantiomer, offering opportunities to exploit this unusual, hindered synthon for synthesis of new chirons.

• G. L. Brown, J. M. Gardiner, A. d’Emanuele, D. Attwood, R. Gibb "Synthesis and characterization of shape persistent polyphenylene dendrimers.” Polymer Preprints, 2006, 47, 660-661.
• J. M. Gardiner, N. R. Panchal, W. T. Stimpson, G. J. Ellames, J. M. Herbert “"Stereoselective Synthesis of 1,2-13C2-L-Fucose, 1,2-13C2-Fucono-g-lactone and 1,2-13C2-Fucono-g-lactol from Non-sugar Starting Material." Synlett 2005, 2685-2687.
• J. M. Gardiner, R. Mills, T. Fessard " Synthesis of model ring systems related to C10-C18 analogues of the Mycalamides/Theopederins." Tetrahedron Lett. 2004, 45, 1215-1217.
• H. Li, P. Williams, J. Micklefield, J. M. Gardiner, G. M. Stephens " A dynamic combinatorial screen for novel imine reductase activity." Tetrahedron 2004, 60, 753-758.
• J. M. Gardiner, P. D. Crewe, G. E. Smith, K. . Veal "Novel Isomenthone-derived 1,3-diol ligands identified through parallel synthesis and screening catalyse an asymmetric aldol reaction", Chem. Commun. 2003, 618-619.
• J. M. Gardiner, P. D. Crewe, G. E. Smith, K. T. Veal, R. G. Pritchard, J. E. Warren "Synthesis, stereostructure and conformations of novel bi- and trifunctional (+)-isomenthone derivatives." Org. Lett. 2003, 5, 467-470
• J. M. Gardiner, A. D. Goss, T. Mahid, A. D. Morley "Synthesis of novel 2,2- and 1,1-linked dimeric ‘Head-to-head’ N-alkoxybenzimidazoles." Tetrahedron Lett. 2003, 44, 511-513.
• J. M. Gardiner, A. D. Goss, T. Mahid, A. D. Morley, R. G. Pritchard, J. E. Warren "Versatile synthesis of N-alkoxybenzimidazoles and N-alkoxypyrimidazoles." Tetrahedron Lett. 2002, 43, 7707-7710.
• "Approach towards C12-oxo analogues of the side chain of pumiliotoxin B/allopumiliotoxin 339A and B." J. M. Gardiner, P. E. Giles and M. M. L. Martin, Tetrahedron Lett. 2002, 43, 5415- 5418.
• "Synthesis and structure of 2-aryl-5,5-disubstituted-1,3-dioxanes and conversion into chiral (1,1,1-trishydroxymethyl) methane derivatives" J. M. Gardiner, P. Mather, R. Morjan, R. G. Pritchard, J. E. Warren, M. L. Cooper, A. El-Rahman S. Ferwanah and O. S. Abu-Tiem, Tetrahedron Lett. 2002, 43, 2091-2094.
• "Synthesis of N-alkoxybenzimidazoles with differentiated C2 and 0- substituents."J. M. Gardiner, J. Procter, Tetrahedron Lett. 2001, 42, 5109-5111.
• "Unexpected Diastereoselectivity in AD of an L-Proline-Derived 1,1-Disubstituted Alkene" J. M. Gardiner, S. E. Bruce, Tetrahedron Lett. 1998, 39, 1029-1032.
• "Synthesis and Proof of Stereostructure of a New (+)-Isomenthone-derived Homochiral 1,3-Diol" J. M. Gardiner, J. H. Chughtai, I. H. Sadler, Tetrahedron: Asymmetry 1998, 9, 599-606.
• "New Homochiral Ketocalcohols from Aldol Reactions of Isomenthone and Reversal of Diastereoselectivity" J. H. Chughtai, J. M. Gardiner, S. G. Harris, S. Parsons, D. W. H. Rankin, C. H Schwalbe, Tetrahedron Lett. 1997, 38, 9043-9046.
• "Structure-Activity Relationships of Anti-HIV-1 N-Alkoxy and N-Allyloxy-Benzimidazoles." TM Evans, JM Gardiner, N Mahmood, M Smis Bioorg. Med. Chem. Letts. 1997, 7, 409.
• "Diastereospecific Dihydroxylation and Highly Efficient Kinetic Resolution of cis/trans-2,6-Dimethylbenzlidene Cyclohexane." JM Gardiner, M Norret, IH Sadler J. Chem. Soc., Chem. Commun. 1996, 2709.

Details of all lecture courses, full slide shows, handouts etc. are available from the Chemistry Intranet link