New Iridium-catalysed Methods for C-H Activation and Hydrogen-Isotope Exchange towards Labelled Oligonucleotides and Other Heterocycles

Lead Research Organisation: University of Strathclyde
Department Name: Pure and Applied Chemistry

Abstract

New Iridium-catalysed Methods for C-H Activation and Hydrogen-Isotope Exchange towards Labelled Oligonucleotides and Other Heterocycles of Elevated Importance in Drug Discovery.

Recently established iridium species from the Kerr laboratories at Strathclyde have emerged to become some of the most active species in isotope labelling chemistry, an area of significant importance within drug design and synthesis.
Building on these studies, it is now proposed that, as part of extended collaborations with AstraZeneca, this field of iridium catalysis is further and extensively diversified, in terms of catalyst structure, key substrate scope, and mode of labelling.
The objectives of this research project are to:
- Extend the recently-developed sp3 labelling towards oligonucleotide units of direct importance and relevance to AstraZeneca;
- Expand directed sp2 labelling to an appreciably broader range of pharmaceutically-important N-heterocycles; and
- Develop a general and presently sought-after method for the non-directed, C-2 labelling of pyridines.
The research described in this programme of work will deliver a flexible range of stable, highly active catalysts of appreciable utility in ongoing selective and functional group tolerant C-H activation and hydrogen isotope exchange processes. Capitalising on emerging techniques from Strathclyde laboratories, a variety of labelled new chemical entities will become accessible via this collaborative research project. More specifically, this will include extremely valuable and selectively labelled oligonucleotide units, as well as a series of heterocycles of elevated pharmaceutical importance and potential application in bioconjugation processes. As part of these research approaches and as routinely applied within our laboratory in this area, the application of computational methods combined with experimental mechanistic modelling and kinetic studies will form a core component of this programme.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/R513349/1 01/10/2018 30/09/2023
2268769 Studentship EP/R513349/1 01/10/2019 31/03/3023 Andrew James Dalgleish