Gephyrotoxins, histrionicotoxins and pumiliotoxins from the neotropical frog Dendrobates histrionicus.

Abstract

AbstractThe structure and absolute configuration of a new acetylenic alkaloid gephyrotoxin isolated from skin extracts of the Colombian frog Dendrobates histrionicus, has been determined by Röntgen‐ray crystallography. Gephyrotoxin, previously referred to as HTX‐D, is a novel tricyclic alkaloid, [1 S, 3aS, 5aS, 6S(Z), 9a R, 10 R]dodeca‐hydro‐6‐(2‐penten‐4‐yl)pyrrolo[1,2‐a]quinoline‐1‐ethanol. Dihydrogephyrotoxin, a minor skin constituent, contains a 6‐(2,4‐pentadienyl)substituent. Two further spiropiperidine alkaloids related in structure to histrionicotoxin, (6 R[6α[2S*(Z)],[7β(Z), 8α]]7‐(1‐buten‐3‐ynyl)‐2‐(2‐penten‐4‐ynyl)‐1‐azaspiro [5.5]undecan‐8‐ol), have been isolated from Dendrobates histrionicus: allodihydrohistrionicotoxin which differs from histrionicotoxin in having a 2‐(4‐pentynyl)‐substituent, while allotetrahydrohistrio‐nicotoxin, a minor constituent, has 2‐(4‐pentynyl)‐ and 7‐(1,3‐butadienyl)‐substituents. Three alkaloids related in structure to pumiliotoxin C, ([2 S, 4a S, 5R, 8a R]5‐methyl‐2‐n‐propyl‐cis‐decahydroquinoline), have been isolated from Dendrobates histrionicus. These alkaloids, with molecular weights of 195, 223, and 269, have, respectively, a 2‐butylsubstituent, 2‐propyl and 5‐propyl‐substituents, and 2‐(3,4‐pentadienyl) and 5‐(2‐penten‐4‐ynyl)‐substituents. The last compound was hydrogenated to a dodecahydro‐derivative identical in molecular weight, but not in other properties, with authentic dodecahydro‐8‐deoxy‐histrionicotoxin, which was prepared from histrionicotoxin. Gephyrotoxin, in contrast to histrionicotoxin and pumiliotoxin C, is a muscarinic antagonist.