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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
|CAS Reg. No.||4720-09-6||4678-44-8||4678-45-9||30272-17-4|
|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)-|
|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|
a. Depends on heating rate
b. Specific values not reported.
|Hazard class*||GHS code and hazard statement|
|Acute toxicity, oral, category 2||H300—Fatal if swallowed|
|Acute toxicity, dermal, category 2||H310—Fatal in contact with skin|
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