Gypsogenin Derivatives: An Unexpected Class of Inhibitors of Cholinesterases

Gypsogenin ( 1 ) was obtained by acidic hydrolysis from its saponin. While the parent compound 1 acted as a selective inhibitor for butyrylcholinesterase (from equus) possessing a moderate mixed‐type inhibition of the enzyme, K i values as low as 2.67 ± 0.59 μM were determined for (3β,4α) 3‐ O ‐acetyl‐olean‐12‐ene‐23,28‐dinitrile ( 11 ) and acetylcholinesterase (AChE, from electric eel). Thus, 11 possesses one‐fifth of the inhibitory activity of the “gold standard” galantamine hydrobromide; this compound is one of the first pentacyclic triterpenoids described as a potent AChE‐selective inhibitor.