Pumiliotoxin from Dendrobates pumilio

The Beckmann rearrangement was used as a key step (41% yield, under standard conditions) for the synthesis of the natural alkaloid Pumiliotoxin C 359, which was originally isolated from the skin extracts of Dendrobates pumilio (a strikingly coloured Panamanian poison arrow frog) (equation 139). ( )-Pumiliotoxin C was also synthesized by a similar ring formation process by Mehta and Praveen. ... 

Decahydroquinolines are another important class of alkaloids isolated from the skin of tropical frogs. Frogs of the family Dendrobates pumilio produce highly toxic alkaloids, the pumiliotoxins [58]. Pumiliotoxin C, one of the prominent members of this class of compounds, has a ds-annulated decahydroquinoline structure, whereas toxins of the related family of Dendrobates histrionicus have fraras-annulated decahydroquinoline structures [49]. These decahydroquinoline systems can be synthesized from the galactosylamine auxiliary 2 in a 12-step pathway(see Scheme 33) [59]. 

The Panamanian frog Dendrobates pumilio yielded not only pumiliotoxin C (vide ante) but also pumiliotoxins A and B. The instability of pumiliotoxins A and B under acid conditions has interfered with the preparation of a crystalline salt and many years after the isolation of these alkaloids the structural formulas remained unknown. Pumiliotoxins A and B and many related alkaloids are widely distributed in frogs of the genus Dendrobates. Serendipitously, in searching for a different alkaloid, a major alkaloid with a molecular weight of 251 (pumiliotoxin 25 ID) was isolated from the skin of the Ecuadorian poison frog Dendrobates tricolor. It proved to be a simpler analog of pumiliotoxins A and B, but most importantly, it was possible to crystallize the HC1 salt and consequently to derive its structural formula by X-ray diffraction analysis (37). 

The first decahydroquinoline found in amphibians was isolated, along with two other alkaloids, from skin extracts of a Panamanian dendrobatid frog, Dendrobates pumilio. The three alkaloids were designated pumiJio-toxins A, B, and C (74,75). Pumiliotoxins A and B were quite toxic, and... 

Pumiliotoxin C, a c/s-decahydroquinoline from poison-dart frogs, Dendrobates pumilio. 

In a further study of the pumiliotoxins from the Panamanian frog Dendrobates pumilio the double bond in the side-chain of pumi-liotoxin B has been shown from nuclear Overhauser effects to have the E configuration, and comparison with model compounds showed that the diol group is threo. The three configuration for the... 

Pumiliotoxin B was isolated from the skin secretions of the Panamanian frog Dendrobates pumilio and has been shown to disrupt neuromusclar transmissions by affecting sodium and calcium concentrations. Manaviazar et al. used the Oppolzer sultam in the total synthesis of... 

---