Dendrobates pumilio alkaloids

The first example of this type of alkaloid, compound 535, known hitherto merely as 205B, has recently been isolated from the skin of the Panamanian frog Dendrobates pumilio. The absolute stereochemistry of the natural (—)-alkaloid was first established by the total synthesis of its (+)-enantiomer by a multistage route from the fused piperidine 536... 

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... 

Three novel tricyclic alkaloids (222, 236, and 252A) were isolated from skin extracts of a Panamanian population of the poison frog Dendrobates pumilio. Amidine structures were proposed for these alkaloids in 1987 based on mass spectral and nuclear magnetic resonance spectral analyses (77). However, recent gas chromatographic-FTIR spectra showed that these three alkaloids could not be amidines, since they had no absorption around 1630 cm where amidines show an intense absorption. A reexamination of the nuclear magnetic resonance spectral data and acquisition of new data led to revised structures 153). The simplest member (222) is a spiropentanopyrrolizidine oxime, whereas 236 is the corresponding... 

In dendrobatid frogs, pyrrolidines have been detected only in certain populations of Dendrobates histrionicus and Dendrobates pumilio (/). Pyrrolidine trans-iSH is the only pyrrolidine to occur as a major alkaloid, and it appears only in the most northern populations of Dendrobates histrionicus. In nondendrobatid frogs, 2,5-disubstituted pyrrolidines have not been detected. 

Piperidines, like pyrrolidines, appear to have a very limited distribution in dendrobatid frogs. Piperidine 241D occurs as a major alkaloid in one population of Dendrobates speciosus and as a trace alkaloid in a population of Dendrobates pumilio (1). 2,6-Disubstituted piperidines 225B and 2391 have been detected as trace alkaloids in Dendrobates histrionicus (two populations) and Epipedobates trivittatus (one population), respectively (1). In nondendrobatid frogs, 2,6-disubstituted piperidines have not been detected. 

The isolation and characterisation from a Panamian population of Dendrobates pumilio Schimdt of indoiizidine 223A [25], formerly identified as 1,4-dipropyl quinolizidine [5], established a new type of class A alkaloids the 5,6,8-trisubstituted indolizidines. 

Pumdiotoxins (PTX). Alkaloids isolated from the arrow poison frog Dendrobates pumilio with indolizi-dine (P. A and B) or decahydroquinoline skeletons (P. C). The P. were later also detected in other frogs and toads. ... 

Alkaloid from skin extracts of the Panamanian poison frog Dendrobates pumilio. [a]i, —3.4 (c, 0.16 in MeOH) (hydrochloride). 

Alkaloid from skin extracts of the Panamanian poison frog Dendrobates pumilio. 

In the last decade, aza-Diels Alder reactions were used effectively to synthesize chiral six-member cyclic systems. Maloney and Danheiser reported on a strategy for the total synthesis of quinolizidine alkaloid (—)-217A 285 where aza-Diels-Alder reaction was used as the key step to induce the chirality in the molecule. The sulfonamide 282 prepared from 5-hexenol 281 by multistep procedures was converted into the aza-Diels Alder precursor 283. It underwent an intramolecular hetero Diels-Alder reaction at 130°C to afford cyclic a-amino nitrile 284 with 56-59% yield. From 284 quinolizidine (—)-217A 285 was prepared following simple steps (Scheme 40.63). This alkaloid is present in the skin of small dendrobatid frog, Dendrobates pumilio ... 

Biosynthetically, little is known of the origin of these alkaloids. In a preliminary study, radioactive acetate and mevalonate were incorporated into skin steroids of frogs, while incorporation of these potential precursors into skin alkaloids was not detected (750). Neither radioactive cholesterol nor serine was significantly incorporated into the batrachotoxins. Three species, Phyllobates aurotaenia, Dendrobates pumilio and Dendrobates auratus were used in these exploratory biosynthetic studies. 

Pumiliotoxins and/or allopumiliotoxins are major alkaloids in most species of the dendrobatid genus Dendrobates (1). The exceptions are a few populations of D. pumilio, one population of D. auratus, all the populations of D. histrionicus except those north of or in the Rio San Juan drainage, and D. occultator and D. truncatus. In the dendrobatid genus Epipedobates, pumiliotoxins and/or allopumiliotoxins are major alkaloids in 4 of the 11 species examined, namely, E. erythromus, E. espinosai, E. silverstonei. 

C. CpHzsN,—, 153°C, mIz 195(65), 152(100). OD. Infrared data(7i). Hq derivative. Alkaloid 195C may prove to represent different compounds in different extracts. Major alkaloid in one population of Dendrobates speciosus minor alkaloid in certain populations of D. leucomelus, D. pumilio, and D. speciosus and in D, reticulatus and Minyobates steyer-marki. Detected in a ranid frog (73),... 

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