EPSRC grant for building '3D' molecules using boron chemistry
Dr Ben Partridge, one of our lecturers in Organic Chemistry, has been awarded a research grant by the Engineering and Physical Sciences Research Council, to investigate how boronic esters can be used as precursors to complex "3D" molecules. We asked Ben to tell us about what this research will entail, and how it could go on to benefit the wider scientific community, particularly the pharmaceutical discovery industry.
"The more planar a drug candidate is, the more likely it is to show unwanted side effects and be rejected in clinical trials. It is therefore desirable to build more "three-dimensional" molecules where there are fewer aromatic rings and more alkyl groups. This concept is challenging as there are few general chemical coupling methods to build complex "3D" molecules in a predictable and reliable manner.
"An opportunity to achieve this is through the formation of amines, one of the most common functional groups found in medicinal drugs and agrochemicals. Traditional methods to make (chiral) alkyl amines, such as nucleophilic substitution and reductive amination, are often non-trivial. They suffer from poor control (e.g. over alkylation), require protecting groups to overcome issues of c”hemoselectivity, and are challenging reactions to control stereoselectively.
"We aim to solve these difficulties by developing a Cu-catalysed amination of alkyl boronic esters, enabling access to complex "3D" amines. These organoboron reagents have several favourable properties which benefit this approach. They are air- and moisture-stable chemicals which tolerate a broad range of functional groups. They also show orthogonal reactivity to other common functionality, reducing the need for protecting groups. Plus, they can be prepared stereoselectively, and typically do not racemise under conditions required for catalysis.
"These properties mean that formation of the key amine motif can be carried out at a late-stage in a synthetic sequence. This will enable the efficient preparation of diverse libraries of complex molecules from common boronic ester building blocks. Such technology will enable scientists in medicinal chemistry and agrochemical discovery to explore new chemical space, expediting the discovery of new medicines and crop protections."
Ben is also recruiting a postdoctoral Reasearch Associate to join his laboratory. You can learn more about the vacancy on Ben's website: bmpartridge.wordpress.com.
You can read more about Ben's work in his recent publication in ACS Catalysis, where he and PhD student James Grayson demonstrate the notably selective oxidation of benzylic boronic esters directly to ketones.