Electrochemistry represents one of the most intimate ways of interacting with molecules. This review discusses advances in synthetic organic electrochemistry since 2000. Enabling methods and synthetic applications are analyzed alongside innate advantages as well as future challenges of electroorganic chemistry.

Synthetic Organic Electrochemical Methods Since 2000: On the Verge of a Renaissance

Conventional methods for carrying out carbon–hydrogen functionalization and carbon–nitrogen bond formation are typically conducted at elevated temperatures, and rely on expensive catalysts as well as the use of stoichiometric, and perhaps toxic, oxidants. In this regard, electrochemical synthesis has recently been recognized as a sustainable and scalable strategy for the construction of challenging carbon–carbon and carbon–heteroatom bonds. Here, electrosynthesis has proven to be an environmentally benign, highly effective and versatile platform for achieving a wide range of nonclassical bond disconnections via generation of radical intermediates under mild reaction conditions. This review provides an overview on the use of anodic electrochemical methods for expediting the development of carbon–hydrogen functionalization and carbon–nitrogen bond formation strategies. Emphasis is placed on methodology development and mechanistic insight and aims to provide inspiration for future synthetic applications in the field of electrosynthesis.

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Electrochemical strategies for C-H functionalization and C-N bond formation.

A diverse array of biologically active, lipid-soluble alkaloids have been discovered in amphibian skin. Such alkaloids include the following:  the steroidal samandarines from salamanders, the batrachotoxins, histrionicotoxins, gephyrotoxins, and epibatidine from neotropical poison frogs (Dendrobatidae), the pumiliotoxins, allopumiliotoxins, homopumiliotoxins, and decahydroquinolines from certain genera of anurans from four families (Dendrobatidae, Mantellidae, Bufonidae, and Myobatrachidae), a variety of izidines (pyrrolizidines, indolizidines, quinolizidines, lehmizidines), pyrrolidines, piperidines, various tricyclics (related in structures to the coccinellines), and spiropyrrolizidines from the first three of these four families, the pseudophrynamines from one genus of Australian frogs, and a variety of unclassified alkaloids as yet of undetermined structure. With the exception of the samandarines and the pseudophrynamines, all alkaloids appear to be derived from dietary sources. Although only a few of...

Alkaloids from amphibian skin: a tabulation of over eight-hundred compounds.

The known diversity of dart-poison frog species has grown from 70 in the 1960s to 247 at present, with no sign that the discovery of new species will wane in the foreseeable future. Although this growth in knowledge of the diversity of this group has been accompanied by detailed investigations of many aspects of the biology of dendrobatids, their phylogenetic relationships remain poorly understood. This study was designed to test hypotheses of dendrobatid diversification by combining new and prior genotypic and phenotypic evidence in a total evidence analysis. DNA sequences were sampled for five mitochondrial and six nuclear loci (approximately 6,100 base pairs [bp]; x¯ = 3,740 bp per terminal; total dataset composed of approximately 1.55 million bp), and 174 phenotypic characters were scored from adult and larval morphology, alkaloid profiles, and behavior. These data were combined with relevant published DNA sequences. Ingroup sampling targeted several previously unsampled species, including Ar...

Phylogenetic systematics of dart-poison frogs and their relatives (amphibia: athesphatanura: dendrobatidae)

https://zenodo.org/record/1004771/files/Cushnie%20et%20al%20%282014%29%20post-peer%20reviewed%20version.pdf

Alkaloids: an overview of their antibacterial, antibiotic-enhancing and antivirulence activities.

Brightly colored poison frogs of the family Dendrobatidae contain an alkaloid-based chemical defense against predation. The bright coloration of these frogs is generally considered an aposematic signal to potential predators; however, relatively few studies have specifically tested this hypothesis. Herein we report the results of a field-based experiment designed to test the hypothesis of aposematism in the dendrobatid frog, Oophaga (=Dendrobates) pumilio from the La Selva Biological Station, Costa Rica. We used plasticine frog models to evaluate natural predation rates as a function of color. Predation rates on brown models were almost twice that of red models, suggesting that predators avoid brightly colored frog models. Birds accounted for the majority of attacks on the models. The results of this study provide experimental evidence in support of the hypothesis that bright coloration in dendrobatids functions as an aposematic signal to predators.

/pdf/experimental-evidence-for-aposematism-in-the-dendrobatid-1jvxrq8zhn.pdf

Experimental Evidence for Aposematism in the Dendrobatid Poison Frog Oophaga pumilio

Herein we review what is known about the chemical ecology of poison frogs with a focus on dendrobatid poison frogs. While five anuran families are known to have an alkaloid-derived chemical defense, the dendrobatids have been studied in greatest detail and provides chemical ecologists with a complex model system for understanding how chemical defenses operate in real time and may have evolved through evolutionary time. We describe the diversity of alkaloid defenses known from frogs, alkaloid sequestration, biosynthesis and modification, and we review what is known concerning arthropod sources for alkaloids. There is variation in nearly every attribute of the system and we try to describe some of the challenges associated with unraveling the complexities of this model system.

A review of chemical ecology in poison frogs

A remarkable diversity of bioactive lipophilic alkaloids is present in the skin of poison frogs and toads worldwide. Originally discovered in neotropical dendrobatid frogs, these alkaloids are now known from mantellid frogs of Madagascar, certain myobatrachid frogs of Australia, and certain bufonid toads of South America. Presumably serving as a passive chemical defense, these alkaloids appear to be sequestered from a variety of alkaloid-containing arthropods. The pumiliotoxins represent a major, widespread, group of alkaloids that are found in virtually all anurans that are chemically defended by the presence of lipophilic alkaloids. Identifying an arthropod source for these alkaloids has been a considerable challenge for chemical ecologists. However, an extensive collection of neotropical forest arthropods has now revealed a putative arthropod source of the pumiliotoxins. Here we report on the presence of pumiliotoxins in formicine ants of the genera Brachymyrmex and Paratrechina, as well as the presence of these ants in the stomach contents of the microsympatric pumiliotoxin-containing dendrobatid frog, Dendrobates pumilio. These pumiliotoxins are major alkaloids in D. pumilio, and Brachymyrmex and Paratrechina ants now represent the only known dietary sources of these toxic alkaloids. These findings further support the significance of ant-specialization and alkaloid sequestration in the evolution of bright warning coloration in poison frogs and toads.

https://www.pnas.org/content/pnas/101/21/8045.full.pdf

Formicine ants: An arthropod source for the pumiliotoxin alkaloids of dendrobatid poison frogs

Alkaloids in the skin glands of poison frogs serve as a chemical defense against predation, and almost all of these alkaloids appear to be sequestered from dietary arthropods. Certain alkaloid-containing ants have been considered the primary dietary source, but dietary sources for the majority of alkaloids remain unknown. Herein we report the presence of ≈80 alkaloids from extracts of oribatid mites collected throughout Costa Rica and Panama, which represent 11 of the ≈24 structural classes of alkaloids known in poison frogs. Forty-one of these alkaloids also occur in the dendrobatid poison frog, Oophaga pumilio, which co-occurs with the collected mites. These shared alkaloids include twenty-five 5,8-disubstituted or 5,6,8-trisubstituted indolizidines; one 1,4-disubstituted quinolizidine; three pumiliotoxins; and one homopumiliotoxin. All but the last of these alkaloid classes occur widely in poison frogs. In addition, nearly 40 alkaloids of unknown structure were detected in mites; none of these alkaloids have been identified in frog extracts. Two of these alkaloids are homopumiliotoxins, five appear to be izidines, four appear to be tricyclics, and six are related in structure to poison frog alkaloids that are currently unclassified as to structure. Mites are common in the diet of O. pumilio, as well as in the diets of other poison frogs. The results of this study indicate that mites are a significant arthropod repository of a variety of alkaloids and represent a major dietary source of alkaloids in poison frogs.

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Oribatid mites as a major dietary source for alkaloids in poison frogs.

Poison frogs are chemically defended from predators and/or microorganisms by the presence of alkaloids in dermal skin glands. Over the past 40 years, more than 800 alkaloids, which are generally organized into 28 structural classes, have been identified in several lineages of poison frogs worldwide. Originally, the presence of alkaloids in frogs was thought to be the result of biosynthesis, however research led largely by John W. Daly resulted in the discovery that most of these alkaloids are sequestered unchanged from dietary arthropods. In the present paper, we review the most significant findings and studies that led to the proposal of the 'dietary hypothesis'.

Ralph A. Saporito

Papers

Experimental Evidence for Aposematism in the Dendrobatid Poison Frog Oophaga pumilio

A review of chemical ecology in poison frogs

Formicine ants: An arthropod source for the pumiliotoxin alkaloids of dendrobatid poison frogs

Oribatid mites as a major dietary source for alkaloids in poison frogs.

Arthropod alkaloids in poison frogs : a review of the 'dietary hypothesis'