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The exploitation of upland plant species in the UK as a feedstock for novel conversion to pharmaceuticals - NF0528

Main Objective
A recent review of indigenous plant species in upland areas demonstrated clear potential for exploitation as raw materials for medicinal uses, but concluded that much development work would be required to realise this potential. We have identified flavanoid building blocks as key intermediates that are available from upland crops (especially heather), and that can potentially be transformed into very high value pharmaceuticals. Novel methodologies have been identified to convert flavanoid building blocks into a number of different types of structure with anticipated diverse medicinal potential, including anti-cancer, anti-depressant, anti-viral and therapeutics for Alzheimer's disease. The main objective of this project is to establish the value of upland indigenous plant species as a feedstock for these novel transformations and thereby bring economic and environmental benefits to the upland community.
Policy Relevance
The development of strategies for the creation and exploitation of non-food crops is a recurring theme of recent policy reports (‘Our countryside The Future’, 2000;1 ‘Task Force for the Hills’, 2001;2 ‘Farming & Food: A sustainable Future’, 20023). Attainment of these research goals will assist Defra in its aim of promoting the exploitation of natural resources to ‘sustain and enhance the distinctive environment, economy and social fabric’ of our countryside (White Paper, 2000).
Intended Use of Results
The output from this project will be definitive information about specific ways each upland plant species could be the source of compounds with pharmaceutical potential. This output will be used in two complementary ways: by the upland community to identify changes in management practice which will be required to produce the necessary materials in sufficient amount and by the pharmaceutical industry as a subject for investment.
Objective (i): Identify flavanoids which are available from indigenous upland plant species and which form appropriate starting materials for the transformations to be undertaken in objectives 2-4. (CSL). Objective (ii): Develop the synthesis of diverse chiral flavanoid intermediates of general structure 6, using either monomeric flavanoids (e.g. catechin) or condensed flavanoids (tannins) as starting materials. This will include the use of immobilised nucleophiles to trap flavanoid intermediates on beads or other supports (University of Nottingham). Objective (iii): Examine the use of monomeric flavanoids, including new systems available from (i), in conversions into novel bridged ketone products related to natural products 9-12 (e.g. hyperforin). Additional biomimetic approaches to these compounds will also be attempted by alkylation–electrophilic cyclisation sequences, analogous to the proposed biosynthesis of hyperforin (16 to 9). (University of Nottingham) Objective (iv): Probe the use of monomeric flavanoids, especially new systems available from (i), in generating novel unnatural mimics of oligoflavanoids. This work will range from the use of simple linkers to make `pseudo` biflavanoids, through the use of carbohydrates or amino acids to make more complex systems, and then finally to polymerisations to generate unnatural analogues of tannins. Metathesis reactions will be used as a key means of polymerisation. (University of Nottingham) Objective (v): Establish feasibility of providing adequate amounts of the required starting material flavanoids for conversion into pharmaceuticals (CSL, University of Nottingham). It should be emphasised that in all areas we will focus on pre-competitive, proof of principle, synthetic chemistry. There are no plans for detailed biological screening of compounds at this stage.
Project Documents
• Final Report : The Exploitation of Upland Plant Species In the UK as a Feedstock for Novel Conversion To Pharmaceuticals   (4319k)
• Executive Summary : The Exploitation of Upland Plant Species In the UK as a Feedstock for Novel Conversion To Pharmaceuticals   (150k)
Time-Scale and Cost
From: 2004

To: 2006

Cost: £302,881
Contractor / Funded Organisations
University - Nottingham, Central Science Laboratory
Agricultural Land              
Analytical Chemistry              
Hill Farming              
Fields of Study
Non-Food Crops