Sir John Cornforth obituary

Nobel prizewinning scientist who made a huge contribution in the field of stereochemistryThe distinguished organic chemist and Nobel laureate Sir John Cornforth, who has died aged 96, is renowned for solving the details of the chemistry of the complex biosynthetic pathway in which acetic acid, containing two carbon atoms, is converted in nature into the steroid cholesterol, which contains 27 carbon atoms and has a structure containing four rings, via the non-cyclic triterpene squalene. There are many enzyme-catalysed steps in a biosynthetic pathway, along which simple compounds are modified, converted or joined together into other products, known as intermediates, to eventually yield the end-product of the pathway. The enzymes of the cholesterol pathway have become potential targets for the design of drugs in its clinical control, one such enzyme being HMG-CoA reductase, which is now targeted by statin drugs.Cornforth's initial work was on the late stages of the pathway. By "feeding" samples of acetate labelled with the isotope carbon-14 to rat liver slices, and chemically degrading the samples of cholesterol and squalene produced, he defined the origin of all of the carbon atoms in each of these compounds. These results provided experimental proof of how squalene is cyclised to form cholesterol in nature.In further experiments, which are now regarded as classics of the use of isotopes in biology, Cornforth was able to explain how methyl groups are rearranged during the conve...
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