Alkaloids from Amphibian Skins

Daly JW, Garraffo HM, Spande TF (1999) Alkaloids from amphibian skins. In Pelletier SW (ed) Alkaloids chemical and biological perspectives, vol 13. Pergamon Press, New York, p 1... 

Daly, J. W., Spande, T. F. and Garraffo, H. M. 2005. Alkaloids from amphibian skin A tabulation of over eight-hundred compounds. Journal of Natural Products, 68 1556-1575. 

Daly JW, Spande TF, Garraffo HM (2005) Alkaloids from amphibian skin a tabulation of over eight-hundred compounds. J Nat Prod 68 1556-1575 Denmark SE (1991) In Trost BM, Flemming I (eds) Comprehensive organic synthesis, vol 5. Pergamon, Oxford, p 51... 

During the edition of this manuscript a publication entitled Alkaloids from amphibian skins, by John W. Daly, H. Martin Garraffo and Thomas F. Spande, was published in Alkaloids Chemical and Biological Perspectives edited by S. W. Pelletier, Pergamon, 1999. 

J. W. Daly H. M. Garraffo T. F. Spande, Alkaloids from Amphibian Skins. n Alkaloids Chemical and Biological Perspectives, ... 

Daly JW, Spande TF, Garraffo HM. Alkaloids from amphibian skin a tabulation of over 800 compounds. J Nat Prod 2005 68 1556-1575. 

Gartner M, Weihofen R, Helmchen G. Enantioselective syntheses of 2,5-disubstituted pyrrolidines based on iridium-catalyzed allylic aminations-total syntheses of alkaloids from amphibian skins. Chem. Eur. J. 2011 17(27) 7605-7622. 

Zasloff is quick to note that nobody has a clue how a giant squid or an octopus—which have neither antibodies nor white blood cells called lymphocytes—avoids becoming consumed by microbes Over the years, he and his colleagues have uncovered many frog-made peptides that possess potent microbe-killing properties. Such a chemical defense system operates by virtue of the peptides ability to poke holes in the cell membranes that serve to protect bacteria from the outside world. In addition to the peptides, scientists including Zasloff have found hundreds of other types of molecules called alkaloids in amphibian skin. When inside cells, many alkaloids home in on structures called ion channels—tunnel-like assemblies through which important electrolytes pass. These are key cellular fixtures,... 

In 1999 the late Dr John Daly, the doyen of researchers in the field of amphibian alkaloids, and two of his regular colleagues published a major survey of alkaloids isolated from, or detected in, extracts from the granular glands in amphibian skin. Their review listed over 500 alkaloids, both well characterized and tentative. This survey was followed by a short personal perspective in which Daly described the discovery and identification of biologically active alkaloids in amphibian skin, and the subsequent confirmation of arthropods as the dietary source of many of these compounds. The survey of 1999 was subsequently superseded by an even more... 

The pumiliotoxins, alio- and homopumiliotoxins, are alkaloids isolated from the skin of amphibians, such as neotropical frogs of the Dendrobatidae family, and are believed to serve as a chemical defence against predators. These natural products have interesting pharmacological properties, including myotonic and cardiotonic activities. 

Three of the classes of compounds found from the skin of amphibians have been identified from the skin of bufonids, including Bufo marinus. These are steroids (bufadienolides), biogenic amines (catecholamines, indolylalkylamines and alkaloids) and bioactive peptides and proteins. 

The neotropical dart poison frogs contain a remarkable diversity of alkaloids, and the 2,5-disubstituted decahydroquinolines represent, a major class of these amphibian alkaloids[21]. Isolation of these alkaloids from some ants strengthens a dietary hypothesis for the origin of the above alkaloids that have been detected in extracts of frog skin[22]. In addition, these alkaloids containing both cis and trans ring fusion have been identified as well as diastereomers at the C-2 and C-5 position. 

The 5,8-disubstituted indolizidines and 1,4-disubstituted quinolizidines are the more common structural patterns found in amphibian skin[21]. None of these alkaloids has so far been reported from any other source. In addition, the biological activity of only a few 5,8-disubstituted indolizidines has been investigated due to the isolation in minute quantities from the skin. Among them, the relative stereochemistry of quinolizidine 2071 was anticipated to be 75 by our chiral synthesis of 76[35] followed by stereocontrolled synthesis of 75[36]. A sample of synthetic racemate of 75 had produced the best separations on GC analysis with (3-dextrin chiral column[36]. 

Most amphibian alkaloids are not as complex in structure as the steroidal batrachotoxins and samandarines. Of the 300 known amphibian alkaloids, most have been characterized from the skin extracts of frogs of the family Dendrobatidae and, hence, have been referred to as dendrobatid alkaloids. The major bicyclic classes of dendrobatid alkaloids are the histrionicotox-ins, decahydroquinolines, and pumiliotoxin-A class. Because of the presence of a piperidine ring in most dendrobatid alkaloids, they also have been referred to as piperidine-based alkaloids. 

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... 

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