Neogermitrine, a New Ester Alkaloid from Veratrum Viride1

Journal of the American Chemical Society
1952.0

Abstract

A new triester alkaloid, neogermitrine, possessing hypotensive activity comparable to that of germitrine, has been isolated from Veratrum viride. It was the main active constituent in two batches of root collected during the summer seasons of 1948 and 1949 but was not encountered in a 1947 batch. Neogermitrine (C₃₅H₃₉O₁₁N) is a diacetate-mono-(levo)-α-methylbutyrate of the alkamine germine. Stepwise degradation with dilute methanol yielded first the known diester alkaloid germidine and finally germine. The infrared spectra of germine and its derived ester alkaloids were recorded and found useful for identification. Fractionation of an active concentrate via 24-plate countercurrent distribution (benzene-2 M acetate buffer, pH 5.5) led to neogermitrine's isolation. Saponification confirmed acetic acid and (levo)-α-methylbutyric acid as components, with three acid equivalents establishing its triester structure. Hypotensive activity in anesthetized dogs showed maximum potency in triesters (neogermitrine and germitrine), while germine (0 esters) and germidine (2 esters) had minimal or moderate activity. Infrared spectra distinguished neogermitrine from related alkaloids (isogermine, germidine, germitrine, protoveratrine); it differs from germidine by an additional acetyl group, altering optical rotation and reactivity. Neogermitrine's occurrence varied with collection years, being absent in 1947 but dominant in 1948/1949 batches.

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