A very special letter (dated 1980) not only because of its truly distinguished author but here we have real content. Letters by Nobel Prize winners are not terribly rare but so often are perfunctory, relating to meetings, events or simply lunch. Here we have real, in depth, chemistry. The receiver, Dr Buckel, a distinguished scientist in his own right, may have been rather embarrassed on receipt. Cornforth believes that Buckel had tackled his work from completely the wrong route … indeed Cornforth is puzzled and goes on to set out in great detail his preferred option(s). In our view the content reveals the manner in which Cornforth visualises the solution to the problem from first principles then more complex mechanisms and solutions and alternative options as his thinking develops. The fact of his genius is plain in the writing. We love it.
The only Australian to date to have won the Nobel Prize for Chemistry.
Dear Dr Buckel
Thank you for your letter of 7 October. I was interested by your account of the work with glutaconate, but rather puzzled that you did not try the degradation to malate in the way you say I suggested. I have forgotten the details of our conversation during your very welcome visit, but certainly I would expect direct oxidation of glutaconate to malate by permanganate to be most unfavourable. This is because in glutaconate one has the combination of a double bond deactivated by conjunction with a carboxyl and a strongly activated methylene group. In these circumstances one would expect permanganate to attack the methylene group to a considerable and perhaps predominant extent, before the double bond was attacked. This is why it would be preferable to use a specific agent first to hydroxylate the double bond. Indeed, it should be possible to proceed in high yield to malic acid by making use of the fact that one of the hydroxyl groups will form a lactone. Thus: … chemical formulae.
He goes on …
The opening of the lactone ring is generally faster than the hydrolysis of an ester group (especially a benzoate) so that if you put the acetyl or benzoyl-lactone in hot water and neutralized the acidity as it appeared you should be able to get a clean ring-opening without other chemical changes. I really think you should try this – it seems so much simpler than the routes you have explored.
I will ask at Sittingbourne if they have any chiral acetate left – I brought none of it here. It will be ten years old now and will have lost nearly half its original radioactivity but a specimen tested for chirality about five years ago seemed not to have been racemized by radiolysis or by preservation in the form of aqueous potassium acetate. However, I wonder if this is the best way to make chiral 4-substituted glutamates and I wonder if you could do this from chirally tritiated malate using R-citrate synthetase and malate dehydrogenase, following this by treatment of the citrate with aconitase, isocitrate dehydrogenase etc. This should give you a totally chiral product whereas by starting from acetate you are at the mercy of isotope effects.
Cornforth goes on to offer his help in finding candidates for research, a task he may achieve on Thursday at The Royal Society where he is attending a discussion on glycolytic enzymes. There it is again proof The Royal Society …is the best Club in the World!
Sydney born Cornforth was totally deaf by the age of twenty but already recognised as and exceptional academic. He went to England, Oxford, along with a similarly gifted chemist Rita Harradence, who he later married. His relationship with Rita started over a broken Claisen flask .. Cornforth was a expert glassblower … something that was essential in the aspiring chemist in the 1930’s. Interestingly, there was no place in Australia where one could do a decent PhD in chemistry at that time. Naturally at Oxford Cornforth was in his element. He went on to be the first to synthesise cholesterol and had a hand in stabilising penicillin building on the work of fellow Australian Howard Florey. Cornforth was awarded the Nobel Prize in 1975 and coincidental with being made “Australian of the Year”. Cornforth also won the Davy Medal, Copley Medal, was Knighted and made Fellow of the Royal Society
Scientific gold – Manuscript letter with considerable scientific content by Australian Nobel Prize winner John Warcup Cornforth