Cross-Metathesis Based Routes to Heteroaromatic Systems

Lead Research Organisation: University of Oxford
Department Name: Oxford Chemistry


Chemistry is a dynamic subject that is at the centre of many different scientific advances. Organic chemistry is concerned with the reactivity of carbon in all its different forms and can be viewed as the chemistry taking place within living things. Chemists are constantly looking for new ways of designing and building molecules (synthetic chemistry is molecular architecture) and this proposal describes a short and powerful new way of making valuable molecules using a new type of catalyst. The molecules at the heart of the proposal are heterocyclic aromatic compounds which have special properties and are the building blocks of many known pharmaceutical agents. To underscore the importance of these heterocycles, the 6 types or arene mentioned in the proposal are present in 7 of the top 15 brand name drugs by retail sales in 2008. The novel chemistry proposed here will provide a new, efficient and powerful way of making heteroarenes using catalysis to control functional group incorporation and substitution pattern: this will be of great benefit to both academia and industry. Plans have also been made to screen the compounds that we make for a wide range of biological activity.Given all of the above, it is imperative that we have novel, efficient and powerful methods for making new heterocyclic aromatic compounds so that we can study and use them. In addition, the development and application of new catalysts and catalytic systems is also important because it makes chemical reactions run faster, cleaner and with less waste: this is clearly a good thing for industry and also for the environment.

Planned Impact

The beneficiaries of this research outside of academia include: chemical industry including the pharmaceutical industry; the agrochemical industry; the fine chemical industry. These beneficiaries will be able to exploit the chemistry described in this proposal to achieve the synthesis of heteroaromatic aromatic derivatives in a more efficient way. Heterocyclic arenes are extremely important molecules with many uses (many commercial drugs contain a heterocyclic arene) and, therefore, this regime will allow industry to make commercially valuable compounds in a new way, giving them a competitive advantage. Each of the beneficiaries above improves the quality of life and the wealth of the nation, through the application of novel organic chemistry. Chemical industry plays a big role in the U.K. economy (1999 UK trade surplus in medicines was 2060 million) and the U.K. has a strong pharmaceutical industry, who stand to benefit from this methodology. Clearly, it is important that I engage with potential end-users of this chemistry so that I can ensure the project makes a maximum impact in the most relevant areas of research. I have several plans for publicising the work and for getting industry feedback on our routes to heterocyclic arenes. The easiest way to publicise our work is to deliver lectures in industrial laboratories, followed by a discussion of the potential applications (I have given 9 such lectures at pharmaceutical companies since 2007, and I already have 3 more invitations for 2010). Since appointment in 1994, I have had many CASE type collaborations with industry and sent nearly 30 people to full-time employment in various industrial chemistry laboratories; so I have many relevant contacts within the industrial organic chemistry community. I have been, will continue to be, very active in publicising our methodology and gaining feedback on useful applications of it. The timescale involved in giving a benefit to the end-users of the research is short (months rather than years): as soon as new routes are developed and publicised then they can be used in industrial laboratories. Clearly, routes to established drug candidates are not changed lightly, and it may take longer to make an impact on a drug development scale compared to a medicinal chemistry setting. However, the improvements in efficiency and scalability will be worth it. Note that there is excellent precedent for the metathesis reaction being run on a large scale (multi kilo) for drug development purposes and this bodes well for industrial uptake of our chemistry. Details of our plans for exploitation and collaboration are given in the Impact Plan.


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Description This project was very successful and allowed us to prepare a wide range of valuable aromatic compounds, using the latest cutting edge catalytic reactions. The work was publicised widely with academic articles in international journals and many research talks at venues around the world.
Exploitation Route The project has uncovered work which will be exploited in other grant applications to both EPSRC and industry.
Sectors Chemicals

Description New routes to complex molecules using metathesis reactions
First Year Of Impact 2011
Sector Pharmaceuticals and Medical Biotechnology
Impact Types Economic