Dendrobatid toxin

A stereoselective total synthesis of dendrobatide toxin 251 D was developed by Overman et al.237) involving an epoxidation of the (S)-proline derivative (237) to furnish the oxirane (238) as major product. In their approach towards the total synthesis of the same natural product Thomas et al.238) investigated the stereoselectivity of the epoxide formation from (S)-5-acetylpyrrolidin-2-one and dimethyloxosulfonium methylide. A diastereoselectivity of d.s. 50-60% was achieved 238. ... 

Daunomycinone, 254, 255 Debenzylation, 532 Debromination, 276, 548, 599 Decarboalkoxylation, 301 Decarboraethoxynauclechine. 185 Decarbonylation, 393 Decarboxylation-carbonylation, 392 Dehydroamination, 502 Dehydroamino acids, 6-7 Dehydrocyanation, 173 Dehydrosulfiiration, 62 Dehydroxylation, 127 Dendrobatid toxins, 43 Dendrolasin, 419 Denitration, 547 Deoxoprosophylline, 315 11-Deoxyanthracycline, 113 11-Deoxydauomycinone, 85 Dcoxyfrenolicin, 357 14-Deoxymuristerone, 127... 

Dendrobatid toxins. The first step in a synthesis of ( )-perhydrogephyrotoxin (S, a poison-frog alkaloid) involves a Diels-Alder reaction of 1 and a suitable a.ft-unsulurated aldehyde, which proceeds selectively to give the erafo-adduct 2. Another key step is the selective reduction of a bicyclic imine (3) with LiAlH4 in about 9 1 ratio from the sterically more hindered a-face.2... 

The dendrobatid toxin 25 ID (18) has been synthesized by a new approach which utilizes an iminium-vinylsilane cyclization to produce the (Z)-6-alkylidene-indolizidine ring-system in a stereospecific manner. The key intermediate (19) was prepared from L-proline and converted into toxin 25 ID (18) by reaction with paraformaldehyde and (+)-camphor-10-sulphonic acid in refluxing ethanol. The method is potentially a general one for forming unsaturated azacyclic rings, and it provides a convenient route to the pumiliotoxin A alkaloids.7... 

An elegant application of vinylsilane chemistry reported this year is the clean and stereospecific iminium ion-vinylsilane cyclization to dendrobatid toxin 25 ID shown in Scheme and a spiroannulation synthesis has been described in which the final stage is Lewis-acid-catalysed cyclization of (111) to (112)/ °... 

An iminium ion-vinylsilane cyclization (Scheme 6) provides the basis for a very short synthesis of dendrobatid toxin 25 ID (85) as reported by Overman and Bell. A related iminium ion cyclization [(86) (87)] is a key step in a... 

Overman, L. E., and K. L. Bell Enantiospecific total synthesis of dendrobatid toxin 25ID. A short chiral entry to the cardiac-active pumiliotoxin A alkaloids via stereospecific iminium ion — vinylsilane cyclizations. J. Amer. Chem. Soc. 103, 1851— 1852 (1981). 

ASIDE Alkaloid toxins found in dendrobatid frogs... 

There is some controversy as to whether the frogs produce the toxins themselves as secondary metabolites or whether they are simply processing their food - ants. Dendrobatid frogs raised in captivity lose their toxicity. In fact, chemical analyses of ants similar (but not identical) to those found in the natural habitat show compounds structurally related to the toxins. 

The indispensable contribution of crystallography has been to establish the molecular formulas, the stereoconfigurations, and the absolute configurations of five quite different toxins representative of the five major classes of dendrobatid alkaloids. Each of the five substances had unexpected and novel chemical bonding. Knowledge of the structures from crystal structure analyses led to reevaluations of the spectral properties of analogs and congeners and to the definitions of the structures of more than 200 dendrobatid alkaloids. 

Histrionicotoxins were first discovered in the extremely variable dendrobatid species Dendrobates histrionicus of western Colombia and northwestern Ecuador (54). Histrionicotoxin (238A), allodihydrohistrionico-toxin (285C), and isodihydrohistrionicotoxin (285A) represent major alkaloids in nearly all populations of this species (1,71). In one population from northwestern Ecuador, octahydrohistrionicotoxin (291A) is a major alkaloid (71), whereas in one population from the lower Rio San Juan... 

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... 

One common technique used to examine the toxicity of compounds in the skin of amphibians is to isolate the toxic compounds and inject them into laboratory mice to assay their toxicity. Daly et al. (1978), for example, used this technique to determine the toxicity of dendrobatid frogs. In another study, Brodie et al. (1974) calculated that a single newt Taricha granulosa) contains enough taricha-toxin to kill approximately 25,000 white mice. 

Histrionicotoxin has similar effects in neuromuscular preparations from Rana pipiens and from the frog Dendrobates histrionicus, which produces the alkaloid 10). Muscle contractions are potentiated and muscle action potentials prolonged in both species, but blockade of neuromuscular transmission requires higher concentrations in the Dendrobates than in the Rana. Thus, whatever the site of action of histrionicotoxin it is retained in the frog that produces the alkaloid. It should be pointed out that histrionicotoxin has very low toxicity and that the toxin designation is indeed a misnomer. Thus, the dendrobatid frog probably has no reason to completely protect itself from the action of this class of alkaloids. 

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