(+)-Quassin

Quinones occupy a special place in my heart. And I’m not just talking about the ubiquinone cofactors in my mitochondria. Although the strange-looking quinone functional group is not immediately recognisable to many younger students of organic chemistry, it is essential to much of life on Earth and appears in several life-saving drugs. They also have a long and storied history as both intermediates and targets in total synthesis, including, least notably, in my own PhD studies.

Quinone chemistry in the laboratory shot to fame almost a century ago, when Otto Diels and Kurt Alder discovered their eponymous cycloaddition reaction using benzoquinone as the dienophile, chemistry that would later win them the Nobel prize. In the decades that followed, many landmark total syntheses exploited the use of quinone intermediates, often in Diels–Alder reactions. R B Woodward’s synthesis of reserpine, Yoshito Kishi’s synthesis of tetrodotoxin and Marshall Gates’ synthesis of morphine are just a few ultra-classic textbook examples. The strange thing is, none of these molecules actually contains a quinone! But with relatively little chemistry known, and literature searching so arduous, relying on ‘safe’ and well-precedented quinone Diels–Alder chemistry simply made sense at the time. In addition, the multiple reactive sites on a quinone (or its cycloadduct) provide a great jumping off point for further functionalisation. These days, however, it’s rare to see quinone intermediates en route to non-quinone natural products – which is to say, it’s rare to see them at all. After all, why contort a route to follow old precedent and intermediates that don’t really fit the target?