Enantioselective Late-Stage Modifications of Alkylheterocycles
Lead Research Organisation:
Heriot-Watt University
Department Name: Sch of Engineering and Physical Science
Abstract
This is a PhD research project in chemistry. It concerns the development of new organic reactions for the stereoselective installation of new substituants in the alpha-position of alkylheterocycles. Such alkylheterocycles are prevalent structural motifs in clinical drug molecules, including cilostazol and crizotinib. As heterocycles are typically built up towards the end of a synthetic sequence, our new reactions will be particularly relevant to late-stage modification of these structures. Thus, we anticipate that our new reactions will be of considerable interest to medicinal and pharmaceutical workers.
Organisations
Publications
Wong J
(2020)
Recent advances in benzylic and heterobenzylic lithiation
in Tetrahedron
Wong JYF
(2019)
Lithiation Substitution of Unprotected Benzyltetrazoles.
in Organic letters
Wong JYF
(2019)
Batch Versus Flow Lithiation-Substitution of 1,3,4-Oxadiazoles: Exploitation of Unstable Intermediates Using Flow Chemistry.
in Chemistry (Weinheim an der Bergstrasse, Germany)
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
EP/N509474/1 | 30/09/2016 | 29/09/2021 | |||
1963726 | Studentship | EP/N509474/1 | 30/09/2017 | 29/09/2021 | Yuk Fung Wong |
EP/R513040/1 | 30/09/2018 | 29/09/2023 | |||
1963726 | Studentship | EP/R513040/1 | 30/09/2017 | 29/09/2021 | Yuk Fung Wong |
Description | We have developed novel and convenient methodologies for the modifications of alkylazole compounds (i.e. 1,3,4-oxadiazoles and tetrazoles). Since these heterocyclic motifs are very common in drug-like molecules, these protocols could be use to modify pharmaceuticals bearing these motifs and generate analogues for high-throughput screening of drugs. However, the attempt to conduct these modifications enantioselectively remains to be a challenge, due to the configurational instabilities or the planar nature of the lithiated species. |
Exploitation Route | Following the results generated from this project, it is expected that the field of heterobenzylic metalation reactions will received more attention and continue to expand to other azole compounds. Chemical industries could also be interested to adapt our protocols to manufacture pharmaceuticals, especially our metalation in continuous flow setup which can be conduct at room temperaure. |
Sectors | Chemicals Pharmaceuticals and Medical Biotechnology |