Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn

Automated flow micro-reactors and parallel microwave-assisted synthesis

Donal O'Shea, Pharmaceutical & Medicinal Chemistry. Keywords: pharmacy, pharmaceutical sciences & chemistry.

Continuous flow chemistry has recently emerged as a productive technology for synthetic pharmaceutical chemists. It offers a new tool to accelerate lead discovery and development as it provides reliable control of reaction conditions, such as time, temperature, equivalents of reagents and mixing, and allows exothermic reactions to be performed without the need for cryogenics. In addition, by pressurising the system, reactions can be superheated to give reaction rates significantly faster than in open reflux. This gives microwave-like rate enhancement without the problems associated with microwave-based reactions. On-going research involves the application of fully automated flow micro-reactor systems to sequential compound library generation. The ability of microwave heating to funnel a spectrum of chemical reactivity found in a library into a very short time span has the potential to become a tool for high-throughput synthesis. My research has given rise to a new methodology that can overcome the technical problems associated with microwave parallel synthesis. As a proof of concept we have developed a diversity tolerant multicomponent route to sulfanyl-imidazoles and have shown that a comparable microwave generated library can be achieved with a dramatic reduction in library generation time.

Mentors Donal O'Shea. donalfoshea@rcsi.ie