Grayanotoxins

Happy Halloween!
October 31, 2022
We are scarier than Halloween.
What molecules are we?
Image of Grayanotoxins

Grayanotoxins are highly toxic diterpenoids found in the leaves of several species of the genera Rhododendron, Kalmia, and Leucothoe in the large Ericaceae (heather) family. The compounds get their name from the Japanese plant Leucothoe grayana, which was named after the eminent 19th century botanist Asa Gray.

More than 25 grayanotoxins have been identified in Rhododendron spp. alone. Grayanotoxins I through IV are the most common; their properties are summarized in the fast facts table. The toxic properties of grayanotoxin I, the only article of commerce, are shown in the hazard information table.

The images show the structure of grayanotoxin III. The first four grayanotoxins differ only at positions 10 and 14; the others have various functional groups at other positions.

In the earliest report (1912) of grayanotoxin I, then called andromedotoxin, German phytochemist Otto Tunmann isolated it from tannin and glucose extracted from an Ericaceae plant. Twenty years later, pharmacologist S. W. Hardikar at the University of Edinburgh described the mechanism of “rhododendron poisoning” by this compound.

Many of the early studies on grayanotoxins were performed by Japanese researchers. From 1934 to 1936, Shikiro Miyajima and Sankichi Takei at the University of Kyoto isolated grayanotoxins I–III from L. grayana. Earlier this year, Tuoping Luo and collaborators at Peking University (Beijing) reported the total synthesis of grayanotoxin III.

Grayanotoxin IV did not appear in the literature until 1964, when it was described by William H. Tallent at G. D. Searle (Chicago) as a reaction product under the name Δ10(18)-andromedenol acetate. In 1970, T. Okuno and co-workers at Hokkaido University (Sapporo, Japan), isolated this compound (and grayanotoxin V, for good measure) from L. grayana.

Like the green parts of Rhododendron spp., their flowers, pollen, and nectar also contain grayanotoxins. Honeybees collect the poison-laden pollen and nectar and, if they survive, they convert it to what is familiarly called “mad honey1”. Mad honey is the greatest cause of grayanotoxin poisoning in humans, although in some parts of the world it is made intentionally for use as a traditional medicine or a recreational hallucinogenic substance.

If you want to be scared this Halloween, you can read a lot more about grayanotoxins.

1. Not to be confused with honey contaminated with tutin, the Molecule of the Week for May 2, 2022.

Grayanotoxin fast facts

Grayanotoxin No. I II III IV
CAS Reg. No. 4720-09-6 4678-44-8 4678-45-9 30272-17-4
SciFinder
nomenclature
Grayanotoxane-3,5,6,10,14,16-hexol, 14-acetate, (3β,6β,14R)- Grayanotox-10(20)-ene-3,5,6,14,16-pentol, (3β,6β,14R)- Grayanotoxane-3,5,6,10,14,16-hexol, (3β,6β,14R)- Grayanotox-10(20)-ene-3,5,6,14,16-pentol, 14-acetate, (3β,6β,14R)-
Earliest SciFinder
reference
1912 1934 1936 1964
Empirical formula C22H36O7 C20H32O5 C20H34O6 C22H34O6
Molar mass 412.52 g/mol 352.47 g/mol 370.48 g/mol 394.50 g/mol
Appearance White solid White solid White solid White solid
Melting point 258–270 °Ca 199–200 °C 218 °C (dec.) 177–179 °C
Water solubilityb Soluble Soluble Soluble Soluble

a. Depends on heating rate
b. Specific values not reported.

Grayanotoxin I
hazard information

Hazard class* GHS code and hazard statement
Acute toxicity, oral, category 2 H300—Fatal if swallowed Chemical Safety Warning
Acute toxicity, dermal, category 2 H310—Fatal in contact with skin Chemical Safety Warning

*Globally Harmonized System (GHS) of Classification and Labeling of Chemicals. Explanation of pictograms

Chemical Abstract Service - a division of ACS

Learn more about this molecule from CAS, the most authoritative and comprehensive source for chemical information.

Molecule of the Week needs your suggestions!

If your favorite molecule is not in our archive, please send an email to motw@acs.org. The molecule can be notable for its current or historical importance or for any quirky reason. Thank you!

Stay Ahead of the Chemistry Curve

Learn how ACS can help you stay ahead in the world of chemistry.