Projects

Project 1: Stereodefined Diamine Sulfone Scaffolds based on Intramolecular Cycloadditions of Sulfenic Acids

Academic Supervisor: Dr Richard Grainger (UoB)

Industrial Supervisor: Dr Jörn Saupe (AnalytiCon Discovery)

The Grainger research group at The University of Birmingham, School of Chemistry has a long-standing interest in the generation and use of reactive sulfur species for organic synthesis. This PhD project builds on the tandem sulfoxide elimination – intramolecular sulfenic acid cycloaddition methodology reported by our group for the stereoselective synthesis of cyclic sulfoxides (Org. Biomol. Chem. 2004, 2, 151; Org. Biomol. Chem. 2005, 3, 404). This methodology will be applied to the preparation of novel cyclic sulfur-containing scaffolds incorporating amino groups that can be independently manipulated as points of molecular diversity for library generation. The objectives of the research are to:

i) Develop stereocontrolled routes to enantiopure beta-amino tert-butylsulfoxides.

ii) Investigate the role of amine-stereocentres as control elements in intramolecular sulfenic acid cycloaddition reactions.

iii) Functionalise and diversify novel scaffolds in compound library synthesis. 

Project 2: Intramolecular Hydroalkoxylation Strategies for Morpholine and Oxazepane Scaffold & Library Generation

Academic Supervisor: Dr Liam Cox (UoB)

Industrial Supervisor: Dr Oliver Kunz (AnalytiCon Discovery)

This project will use a range of approaches, including metal-catalysed intramolecular alkyne hydroalkoxylations, to develop routes to cyclic enol ethers.  The enol ether and other points of embedded functionality in these heterocyclic products will then be used to generate structurally diverse scaffolds, in particular spirocyclic systems, which will be further elaborated into novel compound libraries for early-stage drug-discovery applications.  The researcher will develop skills in molecular synthesis, reaction optimisation and compound library generation for early-stage drug discovery.

Project 3: fused bicyclic heterocyclic scaffolds for drug discovery 

Academic Supervisor: Dr John Fossey (UoB)

Industrial Supervisor: Dr Jorg Benningshof (Mercachem)

Homoallylic species have been cyclised to a variety of drug-like ring systems by the team of Dr John S. Fossey. The researcher on this project will explore the scope and utility of these transformations, to target and build unique, elegant and drug-like multi-ring, three-dimensional molecules. Through expansion of various points of diversity, physicochemical properties can be optimised and matched to clinical targets. The appointed researcher will develop skills in organic synthesis, asymmetric synthesis, automated column chromatography and structure elucidation.

Project 4: Convergent Access to Fused Polycyclic Alkaloids by Gold-Triggered Cascading Cycloadditions

Academic Supervisor: Dr Paul Davies (UoB)

Industrial Supervisor: Dr Jorg Benningshof (Mercachem)

A gold-catalysed cascade reaction developed in the Davies group provides rapid and efficient access into complex 3D and sp³-rich molecular architectures. The researcher on this project will explore and develop this route to provide rapid access into fused alkaloid-like heterocyclic scaffolds bearing several points of diversity. The selective transformation of these core structures into different scaffolds will be investigated followed by developing novel compound libraries by elaborating at the incorporated points of diversity. The researcher will develop skills in catalysis and reaction optimisation, structure-reactivity relationships and multi-step synthesis

Project 5: Functionalised Macrocycles as Novel Scaffolds for Library Generation

Academic Supervisor: Dr Liam Cox (UoB)

Industrial Supervisor: Dr J. Benningshof (Mercachem)

Medium-sized rings represent significantly underexplored – but potentially very attractive – starting points for drug discovery.  This project will use ring-expansion strategies to provide a rapid entry into a range of medium-ring heterocycles.  The points of diversity distributed around the macrocycle will then be elaborated to access structurally diverse scaffolds, which will be further decorated to generate novel compound libraries for early-stage drug-discovery applications. The researcher will develop skills in molecular synthesis, reaction optimisation and compound library generation for early-stage drug discovery

Project 6: Rigid 3D Scaffolds by a Diversity-Generating Functional-Structural-Skeletal Elaboration Approach

Academic Supervisor: Dr Paul Davies (UoB)

Industrial Supervisor: Dr Jorg Benningshof (Mercachem) 

This project will design and develop functional building blocks that will provide access to skeletally and functionally diverse systems through application of a suite of complexity-building catalytic methods.  The reactivity of these new building blocks will be explored and routes developed to allow scalable preparation of functionalised motifs suitable for elaboration into compound libraries filling new volumes of chemical space.   The researcher will develop skills in catalysis and reaction optimisation, structure-reactivity relationships and multi-step synthesis.