CCXXXVII.—Pilosine: a new alkaloid from Pilocarpus microphyllus

J. Chem. Soc., Trans.
2004.0

Abstract

Pilocarpine, its stereoisomeride isopilocarpine, and pilocarpidine are the only thoroughly characterised alkaloids from different varieties of jaborandi leaves. Pilocarpidine, which does not contain an N-methyl group but possesses a free imino-group, gives a deep red coloration with Pauly's histidine reagent (sodium diazobenzene-p-sulphonate). The mother liquors from Pilocarpus microphyllus remaining after the separation of pilocarpine and isopilocarpine also exhibited this well-marked red coloration. A large quantity of such residues (representing many tons of leaves) was subjected to investigation to track the base containing the free imino-group using this colour reaction. Separation, mainly depending on the different solubilities of the bases in water, yielded: (1) resinous matter; (2) a sparingly soluble oil giving an intense Pauly reaction; (3) a sparingly soluble crystalline base designated pilosine (yielding 0.007 per cent. of the leaves, which did not give the Pauly reaction); (4) a mixture of pilocarpine and isopilocarpine; and (5) the mother liquor from (4) containing remaining readily soluble bases and giving only a moderate Pauly reaction. All attempts to isolate pilocarpidine from fraction 5 were unsuccessful, thus confirming Jowett's statement that P. microphyllus does not contain pilocarpidine. The base in fraction 2 (with Pauly reaction) was not isolated in crystalline form, but the new crystalline alkaloid pilosine from fraction 3 was characterised and investigated. Pilosine has the empirical formula C₁₆H₁₈O₃N₂ and is a monacid optically active base. It contains an N-methyl group but no methoxyl group, a lactonic grouping (accounting for two of the three oxygen atoms), and a hydroxyl group (the third oxygen atom). Treatment with acetic anhydride removes the elements of water to form a new unsaturated base, anhydropilosine (C₁₆H₁₆O₂N₂), which is a monacid optically active base with a lactonic grouping. When distilled with 20 per cent. aqueous potassium hydroxide, pilosine yields benzaldehyde and a new base pilosinine (C₉H₁₂O₂N₂), a monacid optically active crystalline base. Pilosinine is chemically, solubly, and physiologically similar to pilocarpine and isopilocarpine, and is highly probable to be a glyoxaline derivative and a lower homologue of pilocarpine and isopilocarpine. Physiologically, pilosine has a very weak pilocarpine action, anhydropilosine shows similar behaviour but is somewhat stronger, and pilosinine has a mild pilocarpine action.

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