Dart-poison frogs

Very rapid-acting paralytic neurotoxin that binds to sodium channels of nerve and muscle cells depolarizing neurons by increasing the sodium channel permeability. It is obtained from South American poison-dart frogs (Phyllobates aurotaenia, Phyllobates terribilis). It is insoluble in water but soluble in hydrocarbons and other nonpolar solvents. The dried toxin can remain active for at least a year. However, it is relatively nonpersistent in the environment. 

Ellison earned a master of science in chemistry from the University of California, Irvine. His graduate research involved methods to synthesize poisons extracted from Colombian poison dart frogs. He has a bachelor of science in chemistry from the Georgia Institute of Technology. He is a member of the American Chemical Society and Federation of American Scientists. In addition to his works on weapons of mass destruction, he is the author of a chapter on the hazardous properties of materials in the sixth edition of the Handbook on Hazardous Materials Management, a textbook published in 2002 by the Institute of Hazardous Materials Management. 

Scheme 18.29 Allenic alkaloids isolated from the skin of Dendrobates poison-dart frogs .

The toxic alkaloids of poison dart frogs appear to depend on diet (Daly etal, 1994,2000 Caldwell, 1996). Details are described in Section 10.2.2. 

Daly, J. W., Meyers, C. W., Warnick, J. E., and Albuquerque, E. X. (1980). Levels ofbactra-chotoxin and lack of sensitivity to its action in poison-dart frogs Phyllohates). Science 208,1383-1385. 

Daly, J. W, Garraffo, H. M., Spande, T. F., Jaramillo, C., and Stanley, R. A. (1994). Dietaiy source for skin alkaloids of poison dart frogs Dendrobatidae) Journal ofChemicalEcology 20,943-955. 

In our group the diastereoselective 1,2-addition of organometallic reagents to aldehyde SAMP hydrazones was employed in the synthesis of several alkaloids and we have now extended our method to the efficient asymmetric synthesis of the poison-dart-frog indolizidine alkaloids 2091 and 223J and their enantiomers via a common late-stage intermediate amino nitrile (5R,8R,8aS)-63 [45]. This amino nitrile chemistry had previously been used by Polniaszek and Belmont in the first enantioselective total syntheses of 5,8-disubstituted indolizidine alkaloids [46]. They were able to prepare the indolizidines 205A (65) from 64 in one or two steps (Scheme 1.2.15). 

Epibatidine (5, Figure 11.5), a natural alkaloid isolated by Daly et al.55 from the Ecuadorian poison dart frog, Epipedobates tricolor, has recently proved that the proposed pharmacophores are not complete. Epibatidine is the most potent central nicotinic receptor ligand reported to... 

Some Japanese chemists needed the E,E-diene below for a synthesis of a neurotoxic compound that they had isolated from poison dart frogs. Unfortunately, their synthesis (which used a Wittig reaction—Chapter 14 and later in this chapter) gave only 4 1 E selectivity at one of the double bonds. To produce pure E,E-diene, they equilibrated the ,Z-diene to , by treating with iodine and irradiating with a sun-lamp. 

Histrionicotoxin is a defensive toxin that protects Dendrobates histrionicus from potential predators. These small poison dart frogs inhabit the moist humid floor of tropical rainforests, and are commonly found in western Ecuador and Colombia. Histrionicotoxin acts by interfering with nerve transmission in mammals, resulting in prolonged muscle contraction. 

Recently, Kibayashi s group (85JA5534) elegantly carried out the stereo-controlled total synthesis of gephyrotoxin (skin extracts of neopropical poison dart frog) based upon an intramolecular nitroso Diels-Alder reaction. The hydroxamic acid 365 was treated with tetrapropylammonium periodate... 

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

Gephyrotoxin (106), a constituent of the skin extracts of the poison-dart frog, was synthesized as outlined in Scheme 11. The organoaluminum-promoted Beckmann rearrangement produced an imine, which was stereoselectively reduced (essentially total selectivity) with DIBAL to afford piperidine (109 41% yield). 

Synonyms Fhyllobates toxin Pitohui toxin Ifrita toxin poison dart frog toxin Chemical/Pharmaceutical/Other Class Steroidal alkaloid neurotoxin Chemical Formulas o Batrachotoxin C31H42N2O6 o Homobatrachotoxin C32H44N2O6 o Batrachotoxinin-A C24H35NO5... 

For millennia, indigenous South Americans deliberately used plant-derived arrow poisons such as curare and also toxins from poison-dart frogs, although these preparations were used mainly for hunting similar toxins were used in Africa. The military use... 

Obtained from South American poison-dart frogs. 

Several synthetic approaches toward the poison-dart frog alkaloids, including pumiliotoxin C (56), ge-phyrotoxin (57) and histrionicotoxin (58), have utilized the Eschenmoser reaction in a variety of distinct applications. These structurally related alkaloids are isolated from skin extracts of various Central and South American frogs in the Dendrohates genus and possess neurotoxic properties. Since their initial isolation and characterization, these toxins have attracted considerable attention for both their synthetic challenge and their interesting biological properties. ... 

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