A team of scientists at Emory University developed a new approach for organic synthesis, called carbon-hydrogen functionalization, that can also be applied to drug discovery. Huw Davies, professor of organic chemistry, founding director of the National Science Foundation’s Center for Selective C-H Functionalization, and senior author of the paper says, “Our tools open up whole new chemical space for potential drug targets.”
In the past, organic chemists have limited their focus to the division between reactive molecular bonds and inert bonds between carbon-carbon (C-C) and carbon-hydrogen (C-H), which provide a kind of scaffold for chemical synthesis. Davies’ idea of C-H functionalization means that the C-H bonds become the reactive bonds, rather than the inert bonds. What this means is that C-H functionalization makes chemical synthesis less costly and that it produces less waste.
Davies has published a series of papers on this topic, but the current paper explains how a dirhodium catalyst efficiently synthesizes a bioisostere of a benzene ring (a two-dimensional molecule with a ring of six carbon atoms bonded by single and double bonds which alternate). The bioisostere is like a benzene ring, but it’s three-dimensional, rather than two-dimensional. Having this extra dimension opens up a world of chemical possibilities for drug discovery.
According to Davies, "Our method allows us to easily achieve a reaction on a C-H bond of this bioisostere in a way that does not destroy the scaffold. We can do chemistry that no one else can do and generate new, and more elaborate, derivatives containing this promising bioisostere. It's like getting a new Lego shape in your kit. The more Lego shapes you have, the more new and different structures you can build."