Project Title: Environmentally Friendly Strategies for the Enantioselective Synthesis of Biologically Important Hetero-Spirocyclic Scaffolds
Host Organisation: University of Cape Town, South Africa
“The universe is disymmetric”. This quote by Pasteur refers to the inescapable consequence of the 3-dimensional nature of our world. Thus, the overwhelming majority of natural product/organic molecules made by nature or by chemists are dissymmetric, or in chemistry terms, the molecules are chiral, existing as “left-handed” or “right-handed” structures that are non-superimposable mirror images of each other, known as enantiomers. This is much like our left and right hands which, although resembling each other, often display very different properties and capabilities, particularly in the way they interact with other chiral objects (such as gloves). For this reason it is absolutely essential that organic chemists are able to selectively prepare one enantiomer over the other in order to promote or suppress various properties, depending on the application.
This proposal therefore aims to generate a range of spirocyclic oxindoles, a ubiquitous structural motif found in naturally occurring compounds. Importantly, the aim is to carry out this new chemistry enantioselectively in order to selectively access one enantiomer over the other. Taking inspiration from nature’s ability to use organic molecules catalytically as well as light as an energy source for the synthesis of complex organic molecules, the proposed research will centre around the use of small molecules (organocatalysis) and light energy (photoredox catalysis) to achieve its overall aims. The novel compounds prepared will be submitted for biological investigation, in a range of high throughput enzyme assays and focused on drugs to treat the African disease burden such as malaria, tuberculosis and HIV.