Umbellulone

Umbellulone is a headache-inducing monoterpene ketone found in the leaves of the tree Umbellularia californica, sometimes known as the "headache tree".

It is hypothesized to cause headaches by influencing the trigeminovascular system via TRPA1.

Umbellularia californica is a tree native to California and Southern Oregon.

Botanist Archibald Menzies was the first to collect the oil at the end of the 18th century. In 1826 this tree was classified as a laurel, Laurus regia, by botanist David Douglas.

In 1833 the tree received another classification by Hooker and Arnott, Tetranthera californica. Shortly after that the present name was given by Nuttal, Umbellularia californica. In 1875 Heaney obtained a colorless liquid (oreodaphenol) via fractionation under reduced pressure. This oil of the California laurel possesses a pungent odor.

Stillman (1880) did a fractionation at 215-216 °C. He discovered that inhalation of its fumes can lead to a painful cold sensation and severe headaches. In earlier times the leaves of the tree were used for cures for headaches or stomachaches and even toothaches.

Powers and Lee did in 1904 another fractionation on the oil of the tree at 217-222 °C. This yielded different compounds: pinene, cineol, eugenol, methyl eugenol and a ketone called umbellulone. Umbellulone is the chemical responsible for the headaches induced by the tree. They gave umbellulone the following structural formula:

In 1908 the structural formula was adapted by Tutin, which was corrected later that year by Semmller to give the structural formula which is accepted today: