Caramboxin

Caramboxin (CBX) is a toxin found in star fruit (Averrhoa carambola) and the related bilimbi fruit (Averrhoa bilimbi). Individuals with some types of kidney disease are susceptible to adverse neurological effects including intoxication, seizures and even death after eating star fruit and bilimbi fruit. In 2013, caramboxin was identified as the neurotoxin responsible for these effects.

Caramboxin is a non-proteinogenic amino acid, with a chemical structure similar to the amino acid phenylalanine, but with extra hydroxyl, carboxyl and methoxy substituents, making it also a phenol, a benzoic acid, and a phenol ether. Caramboxin stimulates the glutamate receptors in neurons, being an agonist of both NMDA and AMPA glutamatergic ionotropic receptors with potent excitatory, convulsant, and neurodegenerative properties, resulting in symptoms of central nervous system disorder, including mental confusion, seizures, and status epilepticus.

A possible interaction between caramboxin and oxalic acid in starfruit can lead to both neurotoxic and nephrotoxic effects. Consuming large amounts of starfruit or its juice on an empty stomach is not recommended, even for individuals with normal kidney function. As caramboxin is water soluble, intense hemodialysis has often been used to improve the outcome for patients.

An enantioselective total synthesis of caramboxin was first published in 2024. It involves a catalytic phase-transfer alkylation of a glycine imine by ethyl acetoacetate.