Synthesis of Spirooxindoles and INdoles pharmaceuticals using Metal-Organic Frameworks

Project Information

SINMOF

Grant agreement ID: 750391

DOI

10.3030/750391

Project closed

EC signature date 3 March 2017

Start date 1 June 2017

End date 31 May 2019

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 160 800,00

EU contribution

€ 160 800,00

Coordinated by

KATHOLIEKE UNIVERSITEIT LEUVEN
Belgium

Periodic Reporting for period 1 - SINMOF (Synthesis of Spirooxindoles and INdoles pharmaceuticals using Metal-Organic Frameworks )

Reporting period: 2017-06-01 to 2019-05-31

Summary of the context and overall objectives of the project

This project is expected to establish a two-way knowledge transfer between the host and the applicant in the synthesis of bio-active indole derivatives using the last synthetic strategies of the partner organisation and new high performance hybrid solid catalysts design at the host institution. SINMOF is a pionering and structured effort to comprehensively address the introduction of different immobilised isolated catalytic active sites in porous hybrid host materials to overcome the metal losses occurring with state-of-the-art homogeneous catalysts. Since metal residues are totally unallowed in pharmaceuticals (downstream processing imposes ≤20 ppm of Platinum-Group Metals or < 300 ppm of other metals). The strategies for selective C-H activation using homogeneous catalysts at the partner organisation will be translated, for the first time, to solid hybrid catalysts like MOFs. So far, the performance of state-of-the art MOFs as catalyst has been mainly tested in single acid-base or redox steps, with the host institution as one of the pioneers in the field. SINMOF project will provide novel MOFs that simultaneously host several types active sites, either as part of the lattice, or appended (e.g. covalent linkages). These can be simultaneously active for consecutive steps in a complex multi-step process due to well-positioned active sites in the solid MOF matrix.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

On the one hand, I have coordinated successful international collaborations with research groups in the field of catalysis, chemistry (both computational and experimental) and engineering from Europe and USA, but also within KU Leuven (Prof. Dirk De Vos, Prof. Ivo Vankelecom and Prof. Michiel Dusselier). On the other hand, I have draft and executed, serving as lead author, networks with top researchers across Europe and USA. The new synthetic methodologies of bioactive steroids, propargylamines, (oxo)indoles, uracil derivatives obtained, were published at the highest scientific level as first (or last) and corresponding author in:
(i) The leading general chemistry journal Angewandte Chemie (October 2017) in collaboration with RTI (USA), showing how a stable and non-toxic solid platform catalyst allows for the transformation of bulky steroids under very mild conditions.
(ii) The leading catalysis journals ChemCatChem (cover), Topics in Catalysis and ACS Catalysis (September 2017, August 2018, November 2019) in collaboration with the Granada University (Spain), tuning MOF catalysts through ion exchange with Cu and Pd active sites or producing catalytic amounts of ZnO/CuO nanoparticles on aluminosilicates for the synthesis of substituted propargylamines, indoles, oxindoles and spirooxindoles N-heterocyclic type pharmaceutically relevant scaffolds under cost-efficient/clean conditions.
(iii) The leading journals in sustainable organic chemistry Green Chemistry and Advanced Synthesis and Catalysis (VIP designation and cover) (April 2018 and September 2018), developing eco-friendly synthesis of substituted indoles and uracil pharmaceuticals by using reusable acid ionic liquids or Cu-Pd redox active MOFs.
(iv) One perspective article in Catalysis Science & Technology and one book chapter (October 2017, April 2018), comparing MOFs and Zeolites or MOFs and Enzymes in organic synthesis in ChemCatChem (invited for the special issue “Sustainable and Affordable Chemistry to Meet Future Challenges in the Pharmaceutical Industry”).

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

This project has enhanced my social competence including (self-) management and leadership, necessary to influence in a collaborative multidisciplinary environment, resulting in around 60 citations of the MC derived papers in high quality journals: Angewandte Chemie (IF: 12.1) ACS Catalysis (IF: 11.4) Green Chemistry (IF: 8.6) Journal of Catalysis (IF: 6.8) Chemical Communications (IF: 6.3) Catalysis Science Technology (IF: 5.4) Advanced Synthesis Catalysis (IF: 5.1) ChemCatChem (IF: 4.7) Topics in Catalysis (IF: 2.4). I have further developed communicate the results of the project in international conferences (>10 oral contributions) of the highest quality in chemistry, where interdisciplinary dialogue and networking opportunities very often appear (EuropaCat 2017, EuroMOF 2017, NCCC 2017, TOCAT 2018, ZMPC 2018, EUCHEMS 2018, HYMA 2019, ACS 2019 etc.). Moreover, I also intend to promote my research (and funding sources) to a wider audience through internet dissemination tools, such as twitter (@fgcirujano) or local press, but also in events organized by KU-Leuven, the Spanish Scientists in Belgium organization, Pint of Science and the Falling Walls Foundation to inspire students and encourage other researchers with their career. Some results of the Marie Curie project have been awarded with the XIII Premio Científico Técnico Ciudad de Algemesí for young Spanish researchers, the first finalist of the X SusChem “Innova” award for young Spanish chemists and best contribution of the Dutch Zeolite Association meeting.
Finally, during this MC fellowship I was commited to supervise, support and develop undergraduate and PhD students (Carlos Márquez, Maxime Stalpaert, Simon Smolders, Jannick Vercammen, Guangxia Fu and Chunmei Jia) and I am co-promotor of one MSc student in catalytic technology (Christophe Kussé), working on Pd containing MOFs as catalyst for the synthesis of neurogenic indoles, and two BSc students (Quinten van Hisberg and Fons Dingenen) in the synthesis of mixed-linker MOFs with catalytic applications in biomass valorization at KU-Leuven.

Summary of the work performed during the SINMOF project