265. The alkaloids of Alstonia barks. Part II. A. macrophylla, wall., A. somersetensis, F. M. Bailey, A. verticillosa, F. Muell., A. villosa, blum

Journal of the Chemical Society (Resumed)
1934.0

Abstract

The search for anti-malarial drugs in the genus Alstonia was continued by examining four more species: A. somersetensis, A. verticillosa, A. villosa, and A. macrophylla. A. verticillosa contains a considerable amount of a mixture of sterols and a small amount of echitamine, very similar to A. scholaris. The other three barks all contain, in addition to much amorphous base, an alkaloid which forms well-defined crystalline salts and for which the name villalstonine is suggested as it was first isolated from A. villosa. A. macrophylla contains, besides villalstonine, three other alkaloids: macralstonine, macralstonidine, and base M (present in exiguous amount). Macralstonidine is also present in A. somersetensis, and a new base V has been obtained from A. villosa. Villalstonine, C₄₀H₅₀O₄N₄, has two basic and two non-basic nitrogen atoms, one methoxy- and two methylimino-groups, with its more complex formula confirmed by molecular-weight determination cryoscopically in benzene; hydrolysis with alcoholic potassium hydroxide furnishes an amphoteric substance without a methoxy-group. Macralstonine, C₃₇H₄₂O₄N₄, is crystalline, forms a crystalline sulphate, and has opposite optical rotation signs for the base and sulphate. Macralstonidine, C₄₁H₅₂O₄N₄, contains two methylimino-groups and appears to have a dioxymethylene group. Bases M and V are crystalline but in too small amounts to determine their formulae. All new alkaloids are indole derivatives. Pharmacological experiments with villalstonine hydrochloride showed a slight increase in isolated rabbit uterus movement at 1:6,500-1:12,500, a fall in anesthetized cat blood pressure (less than alstonine sulphate), no action on guinea-pig uterus (1:25,000) or rabbit intestine (1:50,000); its action on bird malaria was undetermined. Alstonia alkaloids fall into three groups: (a) echitamine (many species from Africa, East Indies, Australia), (b) villalstonine (Australian and East Indian species), (c) alstonine (only A. constricta from Australia).

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