Notes on the plant compound picrotoxin (cocculin)

Picrotoxin (Pikrotoxin) is an astringent principle of the fruit (Anamirta cocculus). The commercial product usually melts between 192° and 200°, but after recrystallisation from water invariably yields a product melting at 199-200°; it is extremely bitter and very poisonous, producing similar effects to those obtained with strychnine. Paternò and Oglialoro, Schmidt, and others regard it as a definite compound which is readily decomposed into picrotoxinin (pikrotoxinin) and pikrotin, but, according to the authors (Richard Joseph Meyer and P. Bruger), it is merely a mixture of these two indefinite, but not molecular, proportions, namely, 54-55 per cent, of picrotoxinin and 45-40 of pikrotin. It may be partially separated into the two constituents by boiling with benzene or chloroform, or by treatment with barium hydroxide; the only method which gives anything like quantitative results is that with bromine water.

Picrotoxinin, C₁₅H₁₆O₆, is best obtained from pikrotoxin by brominating the latter, when in hot aqueous solution, with a slight excess of bromine water, and then, by means of zinc dust and acetic acid, removing the bromine from the monobromopicrotoxinin, which crystallises but; it crystallises from hot water in colourless, anhydrous needles, but from cold aqueous solutions in rhombic, plates containing 1H₂O, melts at 200-201°, is readily soluble in all the usual solvents on warming, and also in cold alcohol or chloroform; it is also soluble in alkalies, but is not reprecipitated on the addition of acids. Sulphuric acid develops an intense orange red coloration, and when hydrogen chloride is led into an ethereal solution of the compound, polymerisation occurs, and pikrotoxide, melting at 308-310°, is formed. Aqueous solutions reduce ammoniacal silver nitrate in the cold, but it contains neither an aldehydic nor a ketonic group. It has an extremely bitter taste, and is the active principle of picrotoxin; its specific rotatory power [ a ]D=—5.85°.

Bromopicrotoxinin (Bromopikrotoxinin), C_l5H₁₅BrO₅, which is most readily obtained by adding bromine water to a hot, nearly saturated, aqueous solution of picrotoxinin until the solution remains permanently yellow, may be purified by reerystal-lisation from absolute alcohol; it separates in glistening needles, melts at 259-260° (Schmidt gives 250-255°; Paternò and Oglialoro give 240-250°), and has [ a ]17/D=—132.5°.

Chloropicrotoxinin crystallises from alcohol in a mixture of needles and plates, melting at 272°.

Iodopicrotoxinin, obtained by the action of iodic acid and a solution of iodine in potassium iodide C₁₅ H ₁₄ O ₆Ac₂, as it can readily be obtained by the action of acetic chloride on picrotoxinin; it sublimes in slender needles melting at 254°—255,° and forms an unstable compound with bromine.

Pikrotin, C₁₅H₁₈O₇, is best obtained from the filtrate from bromopicrotoxinin, part separating out on cooling, whilst the remainder may be obtained by evaporation; it can be purified by several extractions with small quantities of hot chloroform, followed by recrystallisation from water; it forms small, felted needles, or thick, rhombic prisms, melting at 248-250°, is readily soluble in absolute alcohol or acetic acid, but only sparingly in ether, chloroform, or benzene. Its specific rotatory power [ a ]D=—64.7°, and it reduces Fehling’s solution, etc., but only on warming. Its molecular formula has been determined by molecular weight determinations and by the analyses of its benzoyl and acetyl derivatives.

Benzoylpikrotin, C₁₅H₁₇O₇BZ, crystallises from absolute alcohol in colourless needles, melts at 236°, and is readily soluble in chloroform, sparingly in ether or alcohol.

Libenzoylpikrotin, obtained when pikrotin (1 mol.) is heated with benzoic chloride (3 mols.) at 190°, crystallises from alcohol in needles melting on a hot aqueous solution of picrotoxinin, crystallises from alcohol in colourless needles and melts at 198-199°.

Dromopikrotoxic acid, C₁₄H₁₆BrO₆*COOH+H₂O, is obtained when 10 percent, potassium hydroxide solution is slowly added to finely divided bromopicrotoxinin suspended in 10 times its weight of boiling water, until all has dissolved; on the addition of hydrochloric acid, the acid crystallises out in colourless needles, melting at 245-246°; it has no bitter taste, and is optically active [ a ]d=—62.6° The calcium salt, (C₁₅H₁₆BrO₇)₂ Ca+5H₂O, potassium salt, with 2H₂O, ammonium salt, and mercurous salt have been prepared.

Picrotoxic acid, C₁₅H_l8O₇, obtained in small amount by the removal of bromine from the bromo-acid by the aid of sodium amalgam in alkaline solution, crystallises from water in needles melting at 229-230°, and has no bitter taste; its aqueous solution has strong reducing properties, and it readily undergoes decomposition iu both aqueous and ethereal solution.

The substance obtained by Paternò and Oglialoro by the action of sodium acetate and acetic anhydride on picrotoxin, and described as an unsaturated acid, is shown to be diacetylpicrotoxinin, at 247-248°. When a large excess of benzoic chloride is employed, no definite product is obtained.

Acetylpikrotin, C₁₅H₁₇ O₇ Ac, crystallises from benzene, alcohol, or acetic acid in glistening plates melting at 244-245°, and is probably identical with the compound described by Paternò and Oglialoro as diacetylpicrotoxinin and melting at 227°. When pikrotin is allowed to remain in contact with acetic chloride for 24 hours at the ordinary temperature, and then heated until complete solution ensues, two compounds are obtained. Anhydrodiacetyh pikrotin, C₁₅H₁₄ O₆ Ac₂, which is precipitated, on the addition of alcohol, in crystalline masses melting above 300°, and diacetylpikrotin, C₁₅H_l6O₇Ac₂, which is obtained as an oil from the alcoholic mother liquor; when it is hot, aqueous solution is allowed to cool, drops of oil separate, which solidify to crystalline needles melting at 207-210°; these contain 2H₂O.

Attempts to convert pikrotin into picrotoxinin by removal of the elements of water have not proved successful.

When warmed with fuming nitric acid, pikrotin yields a nitro-derivative, C₁₅H_l5O₆. No ₂, anhydronitropikrotin, melting at 260°.

J. Ch. S. 1899 A I. 226-227.