GOALI: Utilizing Rapid Assays for Determining Enantiomeric Excess and Catalyst Discovery in Pharma

University Of Texas At Austin, Austin TX

Investigators

Abstract

The creation of new pharmaceuticals remains a primary strategy to combat disease, such as cancer and heart disease. The need for increasingly simple and rapid methods to synthesize and quickly evaluate new molecules for the pharmaceutical industry has arisen due to the advent of new and modern experimental methods. The drug development process requires thousands of chemical reactions to be conducted each and every day. Unfortunately, standard analytical methods needed to verify the structure and the purity of the molecules synthesized are often slow and unable to operate at such a pace. In this project, new and rapid optical techniques reported previously by the Anslyn group are being employed in real-life screening protocols typical of the workflow carried out at Merck, a global pharmaceutical company. This University of Texas-Merck collaboration tests the utility and generality of the methods, while also highlighting their power to benefit industrially-relevant, synthetic organic chemistry efforts in applications beyond pharmaceuticals. The Merck team provides their reactions to the Anslyn group, while the Anslyn group provides their analytical methods to Merck. Dr. Anslyn involves teams of students in a Freshman Research Initiative and Advanced Research Initiative laboratory in parallel projects, with the same goals and deliverables as his graduate research. These activities involve specialized laboratory courses that teach freshman college students the challenges and rewards of scientific discovery, while improving the retention rates of these students in STEM curricula. With funding from the NSF Chemistry Division, Dr. Anslyn of the University of Texas at Austin working with Merck to design and develop rapid chemical assays for enantiomeric excess (ee) that involve three stages referred to as screening, training, and analysis. The screening exploits the previously reported Anslyn multi-component assemblies that report ee values via circular dichroism (CD). The training is performed with enantioenriched samples of the chiral analyte, and involves standard linear calibration curves or chemometric analysis, as necessary. This step creates a protocol specific to a particular analyte, relating the resultant CD ellipticities to ee. Finally, the analysis step determines ee values in a truly high-throughput fashion, commensurate with a rate of hundreds of samples every hour. Each of these protocols is being created for the types of analytes that are of interest to the pharmaceutical community. In addition to the pharmaceutically-relevant compounds, significant effort is directed toward addressing samples in the complex matrices that industry uses. Graduate students at the University of Texas at Austin become familiar with the instrumentation required for and the processes undertaken to support high-throughput experimentation (HTE) within the pharmaceutical industry. Via quarterly visits to Merck, these students gain an understanding for the practical challenges associated with this approach through interaction with industrial scientists. Throughout the process, the scientists from Merck identify new substrates and reaction classes that have the greatest potential to positively impact asymmetric synthesis.