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Synthetic methods and chemical technologies to enhance bioactive molecular discovery

PGR-P-672

Key facts

Type of research degree
PhD
Application deadline
Friday 17 April 2020
Project start date
Thursday 1 October 2020
Country eligibility
UK and EU
Funding
Competition funded
Source of funding
Research council
Supervisors
Professor Nik Kapur and Professor Adam Nelson
Additional supervisors
Professor Steve Marsden
Schools
School of Chemistry, School of Mechanical Engineering
<h2 class="heading hide-accessible">Summary</h2>

In this project, we will develop new flow technologies to enable a broader toolkit of reactions to be exploited in drug discovery. In particular, photoredox-catalysed reactions can enable the elaboration of molecules (including fragments) along vectors that are inaccessible using the standard toolkit. You will investigate the potential of a range of photoredox-catalysed to be performed (and scaled) in flow. These reactions will enable a wide range of substituents to be introduced to saturated nitrogen heterocycles either alpha or beta to nitrogen. The value of the approach will be demonstrated through functionalisation of exemplar fragments of direct relevance to drug discovery. Overall, the new technology may increase the chemical space that may be routinely explored in drug discovery programmes focused on unmet medical needs.

<h2 class="heading hide-accessible">Full description</h2>

<p>The toolkit of synthetic methods that currently underpins drug discovery is remarkably narrow, which limits medicinal chemists&rsquo; ability to explore drug-relevant chemical space.&nbsp; The toolkit has been dominated by ten reaction classes for the past 30 years: these classes enable the functionalisation of heteroatoms (six classes), deprotection (three classes) and Pd-catalysed cross coupling (the Suzuki reaction).&nbsp; Together, the toolkit accounts for around 70% of reactions that are exploited in medicinal chemistry.&nbsp;</p> <p>The dominance of this reaction toolkit impacts directly on current practices in drug discovery.&nbsp; For example, in fragment-based drug discovery, the direct elaboration of fragments is generally only possible the functionalisation of heteroatoms.&nbsp; However, such groups are often important for molecular recognition, meaning that functionalisation can ablate biological function.&nbsp; As a result, elaborated fragments are often synthesised de novo, even though it would be preferable to exploit fragments directly as substrates.</p> <p>In this project, we will develop new flow technologies to enable a broader toolkit of reactions to be exploited in drug discovery.&nbsp; In particular, photoredox-catalysed reactions can enable the elaboration of molecules (including fragments) along vectors that are inaccessible using the standard toolkit.&nbsp; Unfortunately, such reactions can be difficult to scale in batch syntheses, limiting their current impact on discovery practice.&nbsp; The student will investigate the potential of a range of photoredox-catalysed to be performed (and scaled) in flow.&nbsp; These reactions will enable a wide range of substituents to be introduced to saturated nitrogen heterocycles either alpha or beta to nitrogen.&nbsp; The value of the approach will be demonstrated through functionalisation of exemplar fragments of direct relevance to drug discovery.&nbsp; Overall, the new technology may increase the chemical space that may be routinely explored in drug discovery programmes focused on unmet medical needs.</p>

<h2 class="heading">How to apply</h2>

<p>Formal applications for research degree study should be made online through the&nbsp;<a href="https://eps.leeds.ac.uk/chemistry-research-degrees/doc/apply">University&#39;s website</a>. Please state clearly in the research information section&nbsp;that the research degree you wish to be considered for is &ldquo;Synthetic methods and chemical technologies to enhance bioactive molecular discovery&rdquo; as well as&nbsp;<a href="https://eps.leeds.ac.uk/chemistry/staff/4180/professor-adam-nelson">Professor Adam Nelson</a> as your proposed supervisor.</p> <p>If English is not your first language, you must provide evidence that you meet the University&#39;s minimum English language requirements (below).</p> <p><em>We welcome applications from all suitably-qualified candidates, but UK black and minority ethnic (BME) researchers are currently under-represented in our Postgraduate Research community, and we would therefore particularly encourage applications from UK BME candidates. All scholarships will be awarded on the basis of merit.</em></p>

<h2 class="heading heading--sm">Entry requirements</h2>

Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline. The criteria for entry for some research degrees may be higher, for example, several faculties, also require a Masters degree. Applicants are advised to check with the relevant School prior to making an application. Applicants who are uncertain about the requirements for a particular research degree are advised to contact the School or Graduate School prior to making an application.

<h2 class="heading heading--sm">English language requirements</h2>

The minimum English language entry requirement for research postgraduate research study is an IELTS of 6.0 overall with at least 5.5 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid.

<h2 class="heading">Funding on offer</h2>

<div class="cms"> <p><strong>UK/EU</strong> &ndash;&nbsp;Engineering &amp; Physical Sciences Research Council Studentship&nbsp;for 3.5 years. A full standard studentship consists of academic fees (&pound;4,600 in Session 2020/21), together with a maintenance grant (&pound;15,009 in Session 2019/20) paid at standard Research Council rates. UK applicants will be eligible for a full award paying tuition fees and maintenance. European Union applicants will be eligible for an award paying tuition fees only, except in exceptional circumstances, or where residency has been established for more than 3 years prior to the start of the course.&nbsp;&nbsp;Funding is awarded on a competitive basis.</p> </div>

<h2 class="heading">Contact details</h2>

<p>For further information regarding the application procedure, please contact Doctoral College Admissions:<br /> e: <a href="mailto:phd@engineering.leeds.ac.uk">phd@engineering.leeds.ac.uk</a>, t: +44 (0)113 343 5057.</p>


<h3 class="heading heading--sm">Linked funding opportunities</h3>
<h3 class="heading heading--sm">Linked research areas</h3>