Alkyne metathesis: A new tool for the self-assembly of complex molecular architectures
Lead Research Organisation:
University of Edinburgh
Department Name: Sch of Chemistry
Abstract
Project Aims:
To exploit this highly convergent modular synthetic strategy through the synthesis of heteroaryl analogues of
the disorazoles, termed "hetero-disorazoles", positioning alkyne metathesis as an important tool in this field
(catalyst design optimised in collaboration with Prof. A. Furstner, Max Plank Institute, Mulheim, Germany).
Be inspired in our choice of hetero-disorazole targets by rigorous in silico studies to show which analogues
have the highest predicted dimer/monomer and head-to-tail/head-to-head alkyne metathesis coupling ratios
(molecular modelling conducted in collaboration with Prof. J. Goodman, University of Cambridge).
Access a new class of disorazoles which are not covered by the patent literature and which might be more
stable, more synthetically tractable and have enhanced therapeutic potential (phenotypic and RPPA assays
conducted in collaboration with Prof. N. Carragher at the Edinburgh Cancer Research Centre).
Combining in silico design with experimental validation, this project will demonstrate that Mo-catalysed alkyne
metathesis can be used as an effective tool for the rapid self-assembly of complex macrocyclic architectures of
pharmaceutical interest.
To exploit this highly convergent modular synthetic strategy through the synthesis of heteroaryl analogues of
the disorazoles, termed "hetero-disorazoles", positioning alkyne metathesis as an important tool in this field
(catalyst design optimised in collaboration with Prof. A. Furstner, Max Plank Institute, Mulheim, Germany).
Be inspired in our choice of hetero-disorazole targets by rigorous in silico studies to show which analogues
have the highest predicted dimer/monomer and head-to-tail/head-to-head alkyne metathesis coupling ratios
(molecular modelling conducted in collaboration with Prof. J. Goodman, University of Cambridge).
Access a new class of disorazoles which are not covered by the patent literature and which might be more
stable, more synthetically tractable and have enhanced therapeutic potential (phenotypic and RPPA assays
conducted in collaboration with Prof. N. Carragher at the Edinburgh Cancer Research Centre).
Combining in silico design with experimental validation, this project will demonstrate that Mo-catalysed alkyne
metathesis can be used as an effective tool for the rapid self-assembly of complex macrocyclic architectures of
pharmaceutical interest.
Organisations
Publications
Hillenbrand J
(2020)
"Canopy Catalysts" for Alkyne Metathesis: Molybdenum Alkylidyne Complexes with a Tripodal Ligand Framework.
in Journal of the American Chemical Society
Yiannakas E
(2021)
An Alkyne-Metathesis-Based Approach to the Synthesis of the Anti-Malarial Macrodiolide Samroiyotmycin A.
in Angewandte Chemie (International ed. in English)
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/N509644/1 | 01/10/2016 | 30/09/2021 | |||
| 1940702 | Studentship | EP/N509644/1 | 01/09/2017 | 31/10/2021 | Ektoras Yiannakas |
| Description | In May 2019, I was awarded the prestigious and competitive Leverhulme Trust Study Abroad Studentship, that enabled me to undertake a 15 month-long placement in Europe's world-leading institute for catalysis; the Max-Planck-Institut für Kohlenforschung (MPI) in Germany under the supervision of Prof. Alois Fürstner. My project at the MPI focused on the development of novel ligand scaffolds for the development of a new generation of alkyne metathesis catalysts. This subsequently led to the development of a new family of alkyne metathesis catalysts, also known as ''canopy'' catalysts. This was work was recently disclosed in the Journal of the American Chemical Society (doi: 10.1021/jacs.0c04742). The unrivalled catalytic performance of the newly developed catalysts was exemplified by their application in the first total synthesis of the antimalarial macrodiolide Samroiyotmycin A. Synthesis of the natural product target was achieved via a short, concise and scalable nine-step sequence starting from cheap commercially available starting materials. This work is to be submitted for publication soon. In addition, I was selected to the present a poster on this work at the annual RSC - Organic Division poster symposium (2020). |
| Exploitation Route | The new family of well-defined alkyne metathesis catalysts endowed with a distinctive podand topology was developed that is distinguished by good to excellent catalytic activity and a truly remarkable compatibility with exigent functionality. Furthermore, the application of the newly developed catalysts in the total synthesis of antimalarial macrodiolide Samroiyotmycin A, highlights the potential of alkyne metathesis as a versatile and robust tool for the assembly of complex molecular architectures. |
| Sectors | Chemicals |
| Description | A.G. Leventis Foundation Scholarship |
| Amount | £2,750 (GBP) |
| Organisation | AG Leventis Foundation |
| Sector | Charity/Non Profit |
| Country | Cyprus |
| Start | 07/2020 |
| End | 08/2021 |
| Description | AG Leventis Scholarship |
| Amount | £2,750 (GBP) |
| Organisation | AG Leventis Foundation |
| Sector | Charity/Non Profit |
| Country | Cyprus |
| Start | 09/2018 |
| End | 09/2019 |
| Description | Leverhulme Trust Study Abroad Studentship |
| Amount | £21,000 (GBP) |
| Funding ID | SAS-2019-012 |
| Organisation | The Leverhulme Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 09/2019 |
| End | 09/2020 |