Chemical studies upon the vermeerbos, Geigeria aspera Harv. I. Isolation of a bitter principle "geigerin”

Abstract

l. There has been isolated from toxic consignments of Geigeria aspera, Harv. a neutral lactonic bitter principle to which the name Geigerin has been assigned. This substance, though not the true toxic principle, would appear to be not altogether devoid of pharmacological properties. 2. Geigerin has the formula C₁₅H₂₀O₄ and crystallises from water or moist organic solvents with 1 molecule of water of crystallisation. It exhibits isomerism, the melting points of the two varieties, when anhydrous, being 169° and 189° but preliminary softening with liberation of water from the hydrated prisms is observed at about 68° and 76° respectively. No matter which isomer is used, the same optical activity is exhibited in the same solvent. 3. There are some grounds for believing the isomerism to be due to keto-enol tautomerism, although no hydroxyl group could be detected by acetylation under various conditions. 4. Geigerin forms a 2:4 dinitrophenylhydazone in the presence of hydrochloric acid, but attempts to prepare derivatives of the ketonic function in the absence of an acid failed. 5. Potassium permanganate is not decolorised by the substance in the cold neither can any acetone be recovered after the action of chromic acid under the proper conditions for the oxidation of isopropyl side-chains to acetone. Such a group is therefore not present in Geigerin. 6. Cold hydrochloric acid of concentration over 10 per cent. affords a very striking colour reaction with Geigerin. The substance dissolves easily, forming a cherry-red solution which shows absorption bands at 543, 506 and 466 mμ. In time, the colour becomes more brown in tint. 7. Geigerin is a monolactone and the corresponding acid, Geigeric acid, has been prepared and found to crystallise in plates. 8. When Geigerin is boiled for l hour with concentrated hydrochloric acid the cerise colour changes to brown and from the reaction mixture an acid was isolated in the form of its methyl ester melting at 98.5°. 9. From results reported in the following communication, it would appear that Geigerin is closely related, chemically, to the active principle of the plant which causes vermeersiekte. Preliminary degradation experiments indicate that on potash fusion a mixture of liquid rancid-smelling acids is produced, and certain reactions suggest that these may belong to the polymethylene series of compounds. 10. On distillation at low temperature with zinc dust, fluorescent, oily aromatic substances are produced. At 700° naphthalene is formed. 11 . When Geigerin is oxillised by hot alkaline potassium permanganate, there arises an acidic fraction from which the methyl ester of an acid, probably in C₁₀H₁₃O₃ (OCH₃), was isolated in crystalline form, M.P. 115-6⁰, and also a neutral, non-volatile substance soluble in ether and slightly soluble in water, which on treatment with dilute mineral acid in the cold at once liberates acetaldehyde. The exact nature of this material awaits further investigation, but attention is drawn to the analogous behaviour of the acetals. 12. It would appear from the literature that Geigerin is in all probability identical with the substance extracted by Thoms from Chrysanthemum cinerariaefolium in 1891 and named by him "Pyrethrosin". His formula for this substance C₃₄H₄₄O₁₀ was put forward with some reserve. 13. Preliminary pharmacological experiments upon rabbits, sheep and cats are reported.