School of Chemistry

Paul V. Murphy
Professor of Chemistry and Head of School

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Research interests

Synthesis of natural product related tumour growth and angiogenesis inhibitors:

Angiogenesis is a process that provides blood vessels to tumours and developing tissue. Many anti-tumour compounds also inhibit angiogenesis.  The synthesis and evaluation of such molecules (e.g. Migrastatin analogues) is being undertaken in collaboration with Dr. Jacinta O’Sullivan at St. Vincents Hospital in Dublin and with Dr. Evelyn Murphy in the Conway Institute.   A novel strategy for the synthesis of migrastatin and dorrigocin A analogues have recently been developed from D-glucal and inhibitors of tumour cell migration and proliferation identified. ( Chem Eur J, 2008, 1592–1600, Eur J Org Chem 2008, 1953-8)

Carbohydrate based peptidomimetics and application

We are interested in development of alpha-helical mimetics and iminosugar based peptidomimetics (see J. Org. Chem. 2005, 70, 8527-32; ChemMedChem, 2008, 3, 1071-76) as they have potential in a wide range of diseases, including cancer.  During the course of this work novel syntheses of iminosugars are developed ( J. Org. Chem. 2004, 69, 3565-68, Org. Lett., 2005, 7, 2691).  Such compounds have potential application in cancer and as anti-viral agents.  More recently polyhydroxylated macrolides have been synthesised from sugar precursors with a view to generating novel scaffolds for drug discovery ( J. Org. Chem. 2007, 72, 1803 - 1806).   Currently we also have a project on synthesis of echinomycin mimetics and some work is being carried out on the solid phase.

Natural product synthesis

Recently we described a new route to 1-deoxynojirimycin and analogues that involves a cascade sequence that includes the Huisgen cycloaddition of azides and alkenes.  See Organic Letters, 2008, 10 , 3777–3780.  Routes to macrolide natural products are being explored currently.

Stereoselective glycoside and glycolipid synthesis

Current interests include development of 6,1-lactone and related glycuronic acid based donors and new routes to synthesise glycolipids and mimetics that are important in bacteria – host cell recognition.   Such glycolipids have potential as immunostimulants and in cancer.  For recent publications see Angew . Chem. Int. Ed.  2004, 43, 2518 and Chem. Eur. J. 2007, 13, 902-9.  Glycolipid synthesis has recently been achieved by chelation induced anomerisation which includes S-glycolipid anomerisation ( Org. Lett. 2009, 11, 939-942).

Synthesis geometrically defined oligosaccharides and glycoclusters

The presentation of carbohydrates on cell surfaces is implicated in many important biological processes such as inflammation, infection and tumour growth and metastasis.  We are working on the design and synthesis of carbohydrates that have well defined geometrical properties for study of the relevance of this property in biological systems.  We have recently synthesised divalent mannoside and lactoside derivatives that have interesting and diverse structures.  These have been based on glycophane scaffolds and other scaffolds.  These and related compounds have been evaluated for their biological properties.  A collaboration is underway with Professor Hans-Joachim Gabius and Dr. Sabine André in Munich who are interested in sugar-lectin biochemistry. For papers published jointly with the Munich researchers see Organic and Biomolecular Chemistry, 2009,  7, 4715-4725 and J. Org. Chem 2009, in press.  We are members of the SFI funded Alimentary Glycoscience Research Cluster and working on synthesis of anti-infective agents (see http://www.agrc.ie/ ) based on carbohydrate structures.

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