Salamander alkaloids

Habermehl, G. 1966. Chemistry and toxicology of salamander alkaloids. Naturwissenschaften 53, 123-128... 

Synthetic studies on the Salamander alkaloids have been reviewed.67 The synthesis of 18-amino-steroids that are related to the alkaloid batrachotoxin has been discussed.68... 

The biosynthesis of salamander alkaloids starts from cholesterol. Insertion of nitrogen between the carbon atoms 2 and 3 of the steroid skeleton, and hydroxylation of carbon atom 16 is followed by stepwise degradation of the side chain to form alkaloids like samandinin or samandaridin. 

Occurrence Since most A. are nerve poisons they cannot form in larger amounts in the animal world, except in skin glands where they are excreted for specific purposes as neurotoxins (e.g. the amphibian venoms samandarine and other salamander alkaloids, tetrod-otoxin, batrachotoxins, bufotenine and other toad poisons, glomerine, serotonine, histamine, tyra-mine and other biogenic amines). Most A. occur in plants as by-products of amino acid metabolism where they are mostly stored in peripheral parts of the plant (leaves, roots, barks, fruits) and much less frequently in the wood. A. occur only rarely as free bases in plants and are mostly found as salts with oxalic, acetic, lactic, and citric acids, etc. Some higher plant families are... 

Salamander toxins toxins secreted 1 the skin glands of Salamandra maculosa (European fire salamander) and Salamandra atra (alpine salamander). S.t. include the Salamander alkaloids (see), biogenic amines (tryptamine, S-hydroxytryptamine), and high M, substances that cause skin irritation and hemolysis. 

Triterpene (Steroid) Solanum alkaloids Veratrum alkaloids Funtumia alkaloids Holarrhena alkaloids Buxus alkaloids Salamander alkaloids... 

Amphibians have mucus glands over their whole body to provide the mucus needed to keep their skin moist, and fields of granular glands that secrete alkaloid toxins. In addition to these general glands, salamanders possess glands... 

It is difficult to reconcile the unique chemical structure of tetrodotoxin with that of an animal product. Its structure is not related to that of other animal products by any readily recognized biosynthetic scheme. It is not a terpenoid, not obviously formed from amino acid or carbohydrate units, and apparently not constructed from acetate or propionate units. Nor does it resemble any of the various plant alkaloid patterns. It thus appears to be a very unlikely animal product to result from known biogenetic pathways. In this connection the metabolic incorporation of radioactive precursors using torosa and ]C. granulosa salamanders was studied by Shimizu et al. (47). They observed significant isotopic incorporation into amino acids and steroid metabolites, but they found no such incorporation associated with tetrodotoxin. 

Samandarin, molecular formula C19H31NO2, is the major steroidal alkaloid of the skin glands of the fire salamander (Salamandra salamandra), and is extremely toxic. The toxicides of samandarin include muscle convulsions, raised blood pressure and hyperventilation. 

Fio. 2. Structures of samandarine alkaloids isolated from salamanders of the genus Sala-maadra. 

A synthetic alkaloid, isomeric with samandarine, has been erroneously reported to be isolated from a natural source, namely, the salamander Cryptobranchus maximus 37). However, S. Hara has informed us that this alkaloid was never isolated from Nature (see discussion in Ref. 5). It is referred to in Fig. 3 as the Hara-Oka alkaloid. 

The European fire salamander (Salamandra salamandra) and the alpine salamander (Salamandra atra) are the only amphibians known to contain samandarine alkaloids. These are the only two species in this genus. The proposal that extracts of the brilliant black and yellow Australian myobatrachid frog Pseudophryne corroboree contained samandarine alkaloids (52) has proved to be incorrect, and this and other frogs of the genus Pseudophryne instead contain pumiliotoxins and pseudophrynamines (see Sections III,C and VII, A). The major alkaloids of Salamandra salamandra are samandarine, samandarone, and 0-acetylsamandarine. There do not... 

In contrast to dendrobatid alkaloids, which are not present in captive-raised dendrobatid frogs, lire salamanders produce samandarine alkaloids when reared in captivity (G. Habermehl, personal communication, 1989). No apparent differences in alkaloid content occurred for at least three generations. Incubation of secretions from salamander parotoid glands with radiolabeled cholesterol in buffer for 3 days at room temperature led to some apparent incorporation of radioactivity into samandarine alkaloids (53). 

Alkaloids are an important class of compounds that have pharmacological effects on various tissues and organs of humans and other animal species. More than 16,000 are known and most are derived from higher plants. Alkaloids have also been isolated from microorganisms, from marine organisms such as algae, dinoflagellates, and puffer fish, as well as from terrestrial animals, such as insects, salamanders, and toads. 

It has long been known that salamanders are venomous animals just a century ago Zalesky [1) isolated a poisonous substance from the skin glands. This substance behaved like an alkaloid and was named saman-darine though it is now known to be a mixture of alkaloids. 

N 4.59%, D 10.48%. Constitutes together with samandarotle approx 75% of the alkaloid content in the skin glands of the European fire and Alpine salamanders Sola-mandra maculosa resp. a fra Laur., Salamandridae. Isoln Schopf, Braun, Ann. 514, 69 (1934). Structure and configuration Wolf el el al.. Ber. 94, 2361 (1961). 

Shimizu used this version of the Beckmann fragmentation to construct the characteristic A ring of the steroidal alkaloids of salamanders from an androstane-... 

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