Enantioselective synthesis of biologically relevant molecules using catalysis in continuous flow

Post summary
Applications are invited from suitably qualified candidates seeking to pursue a PhD in the area of organic and analytical chemistry with an interest in engineering on a recently funded research project within the Pharmaceutical and Molecular Biotechnology Research Centre (PMBRC) at WIT. This project will include aspects of reactor design and manufacture, organic synthesis, analytical method development and characterisation for the purpose of design, synthesis and evaluation of novel organic catalysts for enantioselective synthetic organic reactions. The project will also include evaluation of biocatalysts for organic reactions generating a researcher with a broad set of skills highly relevant to the Pharmaceutical Industry.
We have previously completed and published studies applying organocatalysis in batch mode and are currently working in this area. Our novel prolinamide catalysts have been applied to the aldol reaction giving high enantiomeric excesses and yield using standard laboratory conditions and glassware. We would now like to extend this work to convert these successful batch enantioselective organocatalysts into flow processes, serving as a proof-of-concept that organocatalysts in batch conditions can be applied to continuous processes, via homogeneous and/or hetereogeneous catalysis conditions.

In a second strand of work, we have successfully screened a library of bacterial isolates and discovered a novel whole cell catalyst, which was found to efficiently catalyse nitrile hydrolysis with remarkably high enantioselectivity. This isolate was subsequently tested with 33 related nitriles. We would also like to adapt this biocatalytic nitrile hydrolysis to flow conditions. The advantages of microbes/enzymes as catalysts when applied in continuous flow reactors are also significant. Residence times are shorter, the reactor can give increased productivity and handling of substrates of low solubility is improved. The consistent, reproducible reaction conditions can lead to purer product.

The project objectives are as follows:
• To design and engineer a laboratory scale flow reactor with appropriate process control and sensing and evaluate in-house catalysts in the synthesis of oxindoles, assessing the product yield, residence time and enantiomeric excess.
• To adapt a microbial isolate for application to the flow reactor for the synthesis of β-hydroxy acids and amides from nitriles.
• To significantly broaden the reaction scope of the most efficient flow system by applying it to both homogeneous and hetereogeneous conditions and train the student to expert level in this area.
• To investigate alternative reactions catalysed in continuous flow such as Mannich and Michael reactions.
• To enhance existing, and create new collaborations with academic and industrial partners to strengthen the research portfolio and international visibility and dissemination of work carried out in the PMBRC
The student will gain experience in several complementary disciplines, including organic chemistry, analytical chemistry and engineering. The student will work within the PMBRC, with a wide range of equipment and expertise available.

Standard duties and responsibilities of the scholarship
With regard to the duties for the academic development of the scholarship student, the following are some examples of these duties but not restricted to:
• Teaching
• Tutorials and outreach programmes
• Laboratory supervision
• Undergraduate mentoring
• Student retention
• Promotional activities and open day events
• Conference and networking organisation

Essential
• Applicants must have experience in the synthesis, characterisation and purification of organic compounds including multi-step chemical synthesis.

• The applicant must be competent in the interpretation of NMR, MS, IR and UV spectra along with preparing samples and where appropriate running experiments to generate spectra. In addition knowledge of the use of HPLC and instrumental software to run such analytical characterisation instrumentation is required.

• Applicants should have an interest in green chemical synthesis and use of new more environmentally friendly methods to synthesise pharmaceutical intermediates as well an interest in reactor design and engineering

• A good level of generic skills such as literature review skills, use of on-line databases, report writing would also be required.

Desirable
• Knowledge of scientific Database searching, literature review writing and good scientific writing skills.
• Experience on the use of chemical drawing software packages, reference management software
• Knowledge of pharmaceutical science, synthesis of pharmaceutical drugs and experience in analytical characterisation techniques.
• The candidate has completed an undergraduate project or equivalent in synthetic chemistry or has gained relevant synthetic experience within the pharmaceutical industry.
• Experience of method development for HPLC, GC, LC-MS or GC-MS.
• Experience in the operation of analytical instrumentation such as HPLC, GC, GC-MS, LC-MS, NMR and the use of control software for such instrumentation.