Dr. Peter B. Wyatt,
MA DPhil (Oxon), CSci CChem MRSC

Senior Lecturer in Organic Chemistry

School of Biological & Chemical Sciences
Queen Mary, University of London
Walter Besant Building, Mile End Road
London
E1 4NS
Tel: +44 (0) 20 7882 3267
Fax: +44 (0) 20 7882 7427
email: P.B.Wyatt@qmul.ac.uk

Research Interests

•  Stereoselective synthesis of C-glycosides with pharmaceutical relevance

•  Organic electrochemistry

•  Synthesis of amino acid analogues

•  Asymmetric cycloaddition reactions of phosphonic acid derivatives

•  Anti-cancer drugs and their metabolites

•  Plant polyphenols of medicinal significance

•  Ligands for organic light-emitting diodes

C-Glycoside synthesis

There is a growing appreciation of the importance of oligosaccharides as recognition elements in biology ( e.g. in the processes giving rise to bacterial infection and inflamation). However, natural sugars do not usually make good drugs because sugar-receptor interactions are relatively weak and glycosidic linkage is too easily metabolised. We are exploring new chemical methods for the synthesis of stable, unsaturated carbohydrate analogues (e.g. compound 1 , reference 6; compound 2 , reference 8) for use in counteracting biological targets such as cholera toxin.

Organic Electrochemistry

Electrochemistry provides a controlled and environmentally friendly way of adding electrons to organic molecules without generating metal salts as by-products. Reduction of chiral phenazine derivatives such as 3 produces strongly basic radical ions which can be used to bring about the asymmetric ring opening of epoxides (reference 7).

Synthesis of Amino Acid Analogues

B eta amino acids are homologues of the usual alpha amino acids and are of interest because they give rise to peptides with well defined secondary structure and resistance to hydrolysis by enzymes.

We are interested in histidine analogues such as 4 (reference 2) because of the unique hydrogen-bonding and catalytic properties of the imidazole side chain.

Asymmetric cycloaddition reactions of organophosphorus compounds Phosphonic acid derivatives are biologically relevant because of their resemblance to phosphate esters and their ability to mimic the tetrahedral transition state geometry during ester and amide hydrolysis. We are exploring the use of addition reactions to unsaturated phosphonates such as 5 as a way to prepare enantiomerically pure phosphonic acid derivatives.

For an example of our published work on phosphonates please see reference 1.

Anti-cancer drugs and their metabolites

We are engaged in the chemical synthesis of reference samples of anti-cancer drug metabolites. These are used as standards for quantitative analysis of drug metabolism in cancer patients at St Bartholomew's Hospital. In addition many of the novel compounds prepared in our laboratory are screened for anti-cancer activity by Cancer Research UK.

Plant polyphenols of medical significance

Cardiovascular disease is a major cause of illness and death in developed countries. However, there are significant local variations: the UK population is at especially high risk, whilst the relatively low incidence in France (the 'French Paradox') appears to be associated with the consumption of plant polyphenols, particularly those present in the grape seeds used to produce red wine. We have recently started to collaborate with medical colleagues in an attempt to improve understanding of the interaction between the grape seed polyphenols and cells lining the blood vessels. We wish to prepare fluorescent derivatives of these polyphenols to enable cell-polyphenol interactions to be studied. Ultimately we hope to use the knowledge gained to devise new pharmaceutical agents for the treatment of cardiovascular disease.

Ligands for organic light-emitting diodes

In association with colleagues in the Physics Department at Queen Mary we are engaged in the synthesis of new lanthanide complexes for use in the production of organic light-emitting diodes.

Selected Recent Publications

1. Synthetic and Structural Chemistry of Enantiomerically pure 1-Phenyl-2-carboxyethylphosphonic acid and its Derivatives,

S. Gardner, M. Motevalli, K. Shastri, A. C. Sullivan and P. B. Wyatt , New . J. Chem ., 2002, 26 , 433-439.

2. The Homologation of Histidine,

A. Kumar, S. Ghilagaber, J. Knight and P. B. Wyatt , Tetrahedron Lett ., 2002, 43 , 6991-6994.

3. Tin Cyanides and Fulminates (Nitrile Oxides),

P. B. Wyatt in Science of Synthesis , Volume 5, Ed M. Moloney and E. J. Thomas, Thieme, Stuttgart, 2003, Section 5.2.16.

4. Acylstannanes [Including, S, Se and Te analogues],

P. B. Wyatt in Science of Synthesis , Volume 5, Ed M. Moloney and E. J. Thomas, Thieme, Stuttgart, 2003, Section 5.2.17.

5. Imidoylstannanes, Diazostannanes, Tin Isocyanates and Tin Isothiocyanates,

P. B. Wyatt , in Science of Synthesis , Volume 5, Ed M. Moloney and E. J. Thomas, Thieme, Stuttgart, 2003, Section 5.2.18.

6. C -Glycosylidene derivatives ( exo -glycals): their synthesis by reaction of protected sugar lactones with tributylphosphonium ylids, conformational analysis and stereoselective reduction,

M. Gascón-López, M. Motevalli, G. Paloumbis, P. Bladon and P. B. Wyatt , Tetrahedron , 2003, 59 , 9349-9360.

7. Generation of strong, homochiral bases by electrochemical reduction of phenazine derivatives,

A. M. Alonso, R. Horcajada, H. J. Groombridge, R. Mandalia, M. Motevalli, J. H. P. Utley and P. B. Wyatt , Chem. Commun ., 2004, 412-413.

8. Synthesis of Propargyl C-glycosides using Allenyltributylstannane,

K. L. Chan, G. S. Coumbarides, S. Islam and P. B. Wyatt , Tetrahedron Lett. , 2005, 46 , 61-65.

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