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OLEFIN METATHESIS AS A PRACTICAL SYNTHETIC TOOL

Final Report Summary - EUMET (Olefin metathesis as a practical synthetic tool)

Executive summary:

By exploring the potential of olefin metathesis over the past four years, the EUMET project was able to create science that went from being useful in a laboratory on a small scale, to its application in industry in the synthesis of a drug candidate for the treatment of hepatitis C (TMC435 or Simeprevir) and a prototype process for its application in the oil industry. Six new commercially available catalysts were also developed. These catalysts surpass in activity the state-of-the-art complexes before the start of the project. This project demonstrated the synergistic effect of industry and academia working together to achieve a common goal: the design, synthesis and commercialisation of new olefin metathesis catalysts. The project was composed of seven academic and three industrial partners and thanks to considerable effort and constant collaboration between the partners it achieved all the targets and in many cases the results exceeded the expectations.

As a simple gauge of the impact of the work performed during the grant period, the catalyst used in the production of Simeprevir has saved an estimated 360 to 540 days in launching the drug. This time saving alone can be estimated to have an economic impact of 360 to 540 million dollars! The European Commission's (EC) investment in EUMET was a very good one indeed.

Potential impact:

The work carried out under the EUMET consortium has the potential to be exploited and has great economic and social repercussions.

From a social perspective, the pharmaceutical partner, Janssen, estimates a times saving of 1 to 1.5 years in bringing a product to market by the use of an olefin metathesis catalyst; a new drug that will save thousands of lives and will benefit the whole world. Apart from all the people this drug will help, the participation of Janssen in the EUMET project translated into a cost saving of EUR 350 to 500 million, plus costs of goods involved in an alternative synthetic route. This alone, fully justifies the European Union (EU) investment into EUMET.

In addition, the EUMET project funded the career of 12 PhD student and 17 Postdocs, creating a new generation of scientists, that are the future of research in the EU. A considerable number of members from the project now hold academic positions in prestigious institutions across Europe. EUMET also created strong links between the partners that resulted in a high number of collaborative projects that will continue after the end of the project.

In an economic level, three main market fields have been identified: life science applications (pharmaceutical, health, as well as nutrition, flavour and fragrance), polymers, since dicyclopentadiene is known for giving through Ring-opening metathesis polymerisation (ROMP) a very resistant - chemically and physically - polymer, and renewables (specialty chemicals and performance materials made out of renewables). At the end of this project, these three market fields can be characterised and ranked as follows:

1. Life science is a field where catalysts potential seems to be in the multi-100 kg catalyst quantities (500 to 1 000 kg) of catalyst per year, worldwide. This is a long term, high risk market (not many molecules make it to the market although many are invented, especially in pharmaceutical industry), however, it is very lucrative as once a process is in place and it will stay for long enough to pay back the risk.
2. Polymers appear today like a niche market, where ROMP brings some differentiators, but does not allow the ROMP made polymers to significantly outperform the existing ones. It will probably not be more than a multi-100 kg catalyst quantity market.
3. Renewables have in the meantime shown that they can be a viable alternative to oil chemistry. It is still a medium term market, however showing a potential of multi-10s of metric tons worldwide. The necessity of significant investments to be able to manufacture at large scale chemicals out of renewables is to be seen as a moderate to high risk that this market does not develop as fast or as big as foreseen.

The access to intellectual property (IP) covering the technologies necessary to further develop any of these three markets may also be a limiting factor of both the growth and the speed of growth. However, another three to five years are necessary to verify whether metathesis markets can develop enough to generate the expected value.

The EUMET consortium has made significant efforts to disseminate the important scientific results to the public in peer-reviewed journals for a total of 70 publications and counting. Furthermore, EUMET members have and will continue to participate in important meetings presenting the latest advances in olefin metathesis. The international symposium on olefin metathesis and related chemistry (ISOM) XIX, Rennes in July 2011 was attended by a large number of EUMET participants and four EUMET team leaders were invited as speakers.

One of the recent advances made in the course of the EUMET project has been highlighted in Chemical and Engineering News, a publication distributed to all American Chemical Society members (refer to C&E News, 27 September 2010). This highlight was also on the C&E News website. The project was the subject of an article highlighting its impact and success in the magazine Projects, in December 2012.

Project website: http://www.eumet.unisa.it

The EUMET consortium was composed of seven academic research centres and three industries around Europe.

Academics:

1. Team 1: University of St Andrews, Scotland (USTAN) - Team leader: Prof. Steven P. Nolan (snolan@st-andrews.ac.uk via e-mail)
2. Team 2: University of Salerno, Italy (UNISA) - Team leader: Prof. Luigi Cavallo (lcavallo@unisa.it via e-mail)
3. Team 3: University of Warsaw, Poland (UW) - Team leader: Prof. Karol Grela (klgrela@gmail.com via e-mail)
4. Team 4: Leibniz University of Hannover, Germany (LUH) - Team leader: Prof. Andreas Kirschning (andreas.kirschning@oci.uni-hannover.de via e-mail)
5. Team 5: Technical University of Graz, Austria - Team leader: Prof. Christian Slugovc (slugovc@tugraz.at via e-mail)
6. Team 6: University of Gent, Belgium (UG) - Team leader: Prof. Francis Verpoort (Francis.Verpoort@ugent.be via e-mail) (resigned from project with effect from 1 May 2010)
7. Team 7: Ecole Nationale Supérieure de Chimie de Rennes (ENSCR), France - Team leader: Dr Marc Mauduit (marc.mauduit@ensc-rennes.fr via e-mail)

Industrialists:

1. Team 8: Umicore, Germany - Team leader: Dr Angelino Doppiu (angelino.doppiu@eu.umicore.com via e-mail)
2. Team 9: Janssen Pharmaceutica, Belgium - Team leader: Dr Andras Horvath (AHORVATH@its.juj.com via e-mail)
3. Team 10: Institut Francais du Petrole, Energies nouvelles (IFPEN), France - Team leader: Dr Helene Olivier-Bourbigou (helene.olivier-bourbigou@ifp.fr via e-mail)