Samandarine alkaloids

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

One other samandarine alkaloid, namely cycloneosamandaridine, contained a tautomeric aminocarbonyl carbinolamine system, and it was initially thought to be related to samandaridine just as cycloneosamandi-one was related to samandarone 34). However, synthetic cycloneosamandaridine with the carbinolamine formed with a C-19 aldehyde was not identical with the natural compound 36), which thus appears to have a carbinolamine formed with a 6-keto group. Retention of the original name, cycloneosamandaridine, for the natural compound would be unfortunate, since it implies the presence of the cycloneosamandione A,B ring system. The name isocycloneosamandaridine, proposed in Ref. 5, is used in this chapter (see Fig. 2). The name cycloneosamandaridine was retained for the synthetic material, which is shown in Fig. 3 it has not been reported in Nature. 

There is one other natural samandarine alkaloid that does not contain the oxazolidine ring, but instead a seven-membered nitrogen-containing A ring. The structure of this alkaloid, samanine, is shown in Fig. 2. 

Physical and spectral properties of samandarine alkaloids are presented in Table II. Mass spectra of various samandarine alkaloids and derivatives have been presented 38-43). Fragments of C4H8NO (m/z 86) and C4H7NO+ (m/z 85) are typical of oxazolidine-containing samandarine alkaloids. Infrared spectra of various samandarine alkaloids have been published 33,34,43-46 and references therein). Proton magnetic resonance spectra for samandarone, samandenone, and cycloneosamandione have been presented 38,40,41). Samandarine, samandarone, and... 

Fig. 3. Synthetic samandarine alkaloids. These compounds have not been detected in Nature.

Physical and Spectral Properties of Samandarine Alkaloids (33-36,38-47) Samandarine, C,9H3 N02... 

There have been no recent studies on the pharmacology of samandarine alkaloids. Samandarine is a potent local anesthetic 48). Cardiac depressant effects (48,49) and inhibition of binding of a radiolabeled batracho-toxin analog to sodium channels (50) are consonant with the potent local anesthetic activity of samandarine. Samandarine alkaloids show antimicrobial activity (51 and references therein). 

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). 

SAM, samandarines BTX, batrachotoxins HTX, histrionicotoxins PTX, pumiliotoxins aPTX, allopumiliotoxins hPTX, homopumiliotoxins DHQ, 2,5-disubstituted decahydroquinolines 3,5-P, 3,5-d [substituted pyrrolizidines 3,5-1 and 5,8-1, disubstituted indolizidines 1,4-Q, 1,4-disubstituted quinolizidines Epi, epibatidine Pseudophry, pseudophrynamines. With the exception of 3,5-P and 3,5-1, these alkaloids are not known to occur in arthropods (see text). Histrionicotoxins may occur in Minyobates and Mantella, but the evidence is not conclusive. 

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. 

Since some alkaloids exhibit great mammalian toxicity (e.g., batrachotoxin, samandarine), it is obvious that these compounds are capable of initiating severe biochemical and physiological lesions. However, it should not be overlooked that toxicological evaluations of most alkaloids have been implemented by in vitro studies in which the alkaloids have been introduced subcutaneously. On the other hand, in nature, in the absence of a venom apparatus, these compounds would be... 

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. 

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. 

Samandarone (XVI) is the main alkaloid of S. maculosa maculosa in 8. maculosa taeniata it is one of the minor alkaloids. It can readily be obtained from samandarine by oxidation with chromic acid conversely, samandarone is reduced stereospecifically to samandarine by sodium and alcohol or by sodium borohydride. 

Our knowledge of alkaloids in animals is scant. The so-called protoalkaloids (biogenic amines and their derivatives) are widespread in lower animals (194, 195), and the parallelism between plant and animal metabolism is extensive. Betaines, methylated purines (e.g., paraxan-thine (VI) ), derivatives of histidine (spinacine (VII) of the shark), and kynurenic acid (VIII) are not rare in animals. The animal alkaloids, with the exception of samandarine (Vol. V, p. 321), are characterized as weak bases this is perhaps of importance for their excretion. 

Alkaloids which modulate ion channels are tabulated in Table 10. Voltagegated Na+ channels are a target for several steroidal alkaloids, (e.g., batrachotoxinin, samandarine, veratrine, veratridine and zygadenine), indole alkaloids (e.g., ajmaline), aporphines (e.g., dicentrine, liriodenine), quinoline alkaloids (quinine, quinidine), quinolizidine alkaloids (e.g., sparteine, lupanine), and furthermore, for alkaloids present in animals or venoms (e.g., chiriquitoxin, i-conotoxins, dibromosceptrine, gonyauxtoxins, histrionicotoxins, pumiliotoxins, saxitoxin and tetrodotoxin). 

Synthetic studies in Salamandra alkaloids have been reported. In this work, attempted conversion into samandarine of compound (43), prepared from (38), failed. 

The complete paper on the synthesis of samandarine-type alkaloids (6, 401) by Beckmann fragmentation has been published. ... 

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... 

The biosynthetic precursor of these compounds is cholesterol the IV-atom of the alkaloids originates from glutamine. Samandarine causes respiratory impairment, hypertension, cardiac arrhythmia, and hemolysis of red blood particles. It is an effective local anesthetic but is too toxic for medical use (LDjo 1 mg/kg, rabbit). 

Samandarine, samandarone, samanine see salamander steroid alkaloids. 

Salamander contains lot of alkaloids. Samandarine (C19H31NO2) and samandarone (C19H29NO2) are two major alkaloids from European fire salamander (Salamandra salamandra terrestris). These alkaloids are secreted from both the skin and internal organs of the salamander. Other alkaloids are samandaridine, samandinine, cycloneosamandione, samandenone, and samanine. They are steroidal alkaloids and their precursor in the biosynthesis pathway is considered to be cholesterol. Samanine is possible to synthesize synthetically. " ... 

A component that attacks the central nervous system and causes strong convulsions is present in the secretions of the dermal gland of Salamandra maculosa (Salamandridae), a type of salamander that inhabits Europe. The main component of the secretion, samandarine, is a steroidal alkaloid. Samandarine comprises 75% of the total alkaloids and it was isolated together with samandarone [5]. 

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