Frogs, alkaloids

Peters s results for corycavine and corycavamine indicate that these two alkaloids produce narcosis in frogs followed by paralysis of the spinal cord, and in mammals increased secretion of tears and saliva and epileptiform convulsions without increase of reflex irritability they also adversely affect the heart. ... 

According to Biberfeld, palmatine, calumbamine and jatrorrhizine all paralyse the central nervous system in frogs palmatine also produces this effect in mammals and differs from the other two in stopping respiration, probably by paralysis of the respiratory centre. All three alkaloids lower the blood pressure on intravenous injection, palmatine being the most active. 

As these substances are difficult to isolate and to distinguish, particular importance attaches to their colour reactions and to their relative paralysing potencies these and other data for the ten alkaloids are summarised in the table (p. 384), the paralysing potencies being given in micro-grammes (y) per frog. 

The curarising dose, expressed in mgm./kilo for frogs, recorded by Karrer and Schmid for these four alkaloids, is as follows C-curarine I, 0-1 calebassine, 0-2 to 0-5 alkaloid A, 0-05 to 0-07 alkaloid B, 0-03 to 0-05 C-toxiferine I, 0-005. 

The total crude alkaloid from tlie soluble reineckate fraction had the low curarising potency 25 mgm./kilo frog. It consisted mainly of quaternary alkaloids and nothing crystalline lias so far been obtained from the non-quaternary portion. 

Same of Alkaloid Potency mgm./kilo..frog l aroe of Alkaloid Potency. mgm./kilo., fr<... 

Strychnicine. This alkaloid, isolated from nux-vomica leaves grown in. lava, forms needles, m.p. 240° dec.), and is characterised by the following colour reaction. When sodium hydroxide solution is added drop by drop to a solution of a salt of the alkaloid in water, the precipitate formed dissolves on addition of more alkali, forming an orange-coloured liquid which develops a violet colour on addition of hydrochloric acid. Strychnicine is scarcely poisonous, but is said to produce tetanus in frogs. 

Several alkaloids have been recorded for plants of this sub-order. From Nymphoea alba Linn., Bures and Plzik isolated nymphoeine, C14H23O2N it is amorphous, has m.p. 76-7°, gives a hydrochloride, m.p. 230° (dec.), contains a hydroxyl group, appears to be a secondary base, and to contain a pyrrole ring. It is toxic to frogs and produces tetanus-like symptoms. 

Asarum europeum L. According to Abdul menev, the root of this plant contains 1-7 per cent, of imcharacterised alkaloid, asarine. The root produces in frogs, rabbits and dogs, acceleration of respiration, nausea and emesis the cardiac activity of the leaves is thought to be due to a glucoside. (Farmatsiya, 1945, 8, No. 4, p. 39 Chem. Abstr., 1946, 40, 7411.)... 

A novel splropentanopyrrolmdine oxime has been isolated from skin extracts of the Panamanian poison frog. This alkaloid can besynthesized via the Michael addi don of cyclop en-tanecarboxaldehyde to nitroethene fScheme 10.19. ... 

The product of the reaction in Entry 8 was used in the synthesis of the alkaloid pseudotropine. The proper stereochemical orientation of the hydroxy group is determined by the structure of the oxazoline ring formed in the cycloaddition. Entry 9 portrays the early stages of synthesis of the biologically important molecule biotin. The reaction in Entry 10 was used to establish the carbocyclic skeleton and stereochemistry of a group of toxic indolizidine alkaloids found in dart poisons from frogs. Entry 11 involves generation of a nitrile oxide. Three other stereoisomers are possible. The observed isomer corresponds to approach from the less hindered convex face of the molecule. 

The dopaminergic potential of the Dendrobium species is, to date, open for exploration. An interesting feature of the Dendrobium species is their ability to elaborate sesquiterpene alkaloids, the chemical structure of which resembles the one of strychnine. One such alkaloid is dendrobine, which is widespread in the genus. Kudo et al. noted that dendrobine, isolated from Dendrobium nobile, exhibits a strychnine-like presynaptic inhibition in frog spinal cord (64). 

A retro-l,3-dipolar cycloaddition followed by an 1,3-dipolar cycloaddition was used for a highly efficient total synthesis of (-)-histrionicotoxin (4-354) (HTX) by Holmes and coworkers [123]. HTX is a spiropiperidine-containing alkaloid which was isolated by Doly, Witkop and coworkers [124] from the brightly colored poison-arrow frog Dendrobates histrionicus. It is of great pharmacological interest as a noncompetitive inhibitor of acetylcholine receptors. 

A similar procedure was applied to the synthesis of quinazolidine 189 from precursor 188 in the total synthesis of the natural product known as ( )-quinolizidine 2071 190, an alkaloid isolated from the skin of the Madagascar mantelline frog Mantella baroni, that shows an exceptional axial stereochemistry for the ethyl group at C-l. Quinolizidine 189 was transformed into 190 by oxidation and two consecutive Wittig methylenations (Scheme 34) <1999CC2281>. 

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. 

The decahydrocyclazine skeleton is also found in the alkaloid 395, currently known only by the designation 261C. This compound bears a passing resemblance to some of the myrmicarins (Section 16.6.5.2), but occurs in the skin of a totally different animal species, namely poisonous frogs of the genus Mantella <2003H(59)745>. 

The first example of this type of alkaloid, compound 535, known hitherto merely as 205B, has recently been isolated from the skin of the Panamanian frog Dendrobates pumilio. The absolute stereochemistry of the natural (—)-alkaloid was first established by the total synthesis of its (+)-enantiomer by a multistage route from the fused piperidine 536... 

The many isolations of stachydrine have not generated much novel chemistry about this alkaloid. One can mention, however, H-NMR and, 3C-NMR data on stachydrine by Atta-ur-Rahman (40). From the pharmacological standpoint, stachydrine has been found to reduce the systolic rate in frogs (55). 

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