Schoenocaulon Alkaloids. I. Active Principles of Schoenocaulon officinale. Cevacine and Protocevine^1,2

Abstract

ACTIVE PRINCIPLES OF Schoenocaulon oficinale 5519seconds. After filtration and drying the yellow solid was leached with 60 ml. of hot acetone. This extract was concentrated to dryness and the residue was then leached with 20 ml. of acetone at 25". The residue from evaporation of this extract was recrystallized twice from 6 ml. of ethanol to give 0.15 g. of yellow prisms, m.p. 241-247' (cloudy). This fraction (VII) was soluble in sodium bicarbonate and contained 17.47% N. Calcd. for CleHgN~0(N0~)3: N, 18.27. C.-To 0.5 g. of the hydroxypyrazine in 20 ml. of sulfuric acid a t 0" was added over ten minutes 0.09 ml. of nitric acid (d. 1.5)in 10ml. ofsulfuricacid. After15minutesatO'the solution was poured into 200 ml. of water and the yellow solid was filtered off. This was boiled a few minutes in 300 ml. of 1% aqueous sodium bicarbonate and after cooling to 25' the mixture was atered. Acidification of the yellow filtrate precipitated a small amount of solid which was leached with 8 ml. of methanol a t 25'. The residue from evaporation of the methanol was recrystallized from 4 ml. of benzene and then from 1.5 ml. of acetone to yield 6 mg. of large yellow granules, m.p. 237-240'.Presumably this is 2-hydroxy-5-nitro3,B-diphenylpyrazine (VIII).On the basis of analogies drawn from the behavior of zygadenine and its esters upon treatment with alkali, the existence of an isomeric, carbonyl-free cevagenine precursor was postulated. In a search for such a precursor, the amorphous fraction of commercial veratrine after removal of cevadine and veratridine was investigated. Fractionation using chromatographic procedures led to isolation of a new alkamine, protocevine, C Z~H~~O~N , isomeric with cevagenine and cevine and a new ester alkaloid, cevacine, C2gH&bOQN, a monoacetate ester of protocevine. Cevacine yields protocevine upon methanolysis, and protocevine is isomerized to cevagenine by mild alkaline treatment. Acetylation of protocevine with acetic anhydride and pyridine yields protocevine triacetate and similar acetylation of cevacine affords the same triester . Acetylation of protocevine with acetic anhydride and perchloric acid yields anhydroprotocevine tetraacetate, and cevadine has been shown to give an analogous tetraester (anhydrocevadine triacetate) under the same conditions. Protocevine can be obtained from cevadine by methanolysis or by alkaline hydrolysis under very mild conditions. Very mild alkaline hydrolysis of veratridine also yields protocevine. It is proposed that protocevine, and not cevagenine, is the parent alkamine of cevacine, cevadine and veratridine.

The interaction of homologous series of alkanols with sodium channels in nerve membrane vesicles

“…The neurotoxins used were the following: citrate-free tetrodotoxin (TTX) (mol wt 319.28) from Calbiochem, San Diego, CA, and veratridine (VER) (tool wt 673.81) purified in our laboratory according to Kupcham et al (1953), from commercial Veratrine obtained from Sigma. Stock solutions of the toxins were prepared as follows: 50 ~M TTX dissolved in 10 mM acetic acid and 37.5 mM VER in 95% ethanol.…”

Insecticidal activity of various 3-acyl and other derivatives of veracevine relative to the veratrum alkaloids veratridine and cevadine

“…Veracevine (3) was obtained from veratrine by mild alkaline hydrolysis according to the method of Pelletier and Jacobs (1953). Cevine, the 3a-epimer of 3, was prepared by alkaline isomerization of 3 (Kupchan et al, 1953; Pelletier and Jacobs, 1953). 4-Ethynylbenzoicacid, 3,4-dimethoxyphenyl isocyanate, and 2,3,3-trichloroacryloyl chloride were prepared as described by Havens and Hergenrother (1984), Brunner and W 6hrl (1934), and Bergmann and Haskelberg (1941), respectively.…”

“…Acylation at C-3 is characterized by a downfield shift of the C-3 proton to -5.1 and -4.9 ppm for aromatic and aliphatic esters, respectively. Acylation at (Kupchan et al, 1953). Changed crystal form at -160 O C .…”

Modes of Action of Potential Phyto-Pesticides from Tropical Plants in Plant Health Management

“…Hormonal balance disruption Azadirachtin Azadiractin indica *Source: El-Wakeil, 2013 Sabadilla (Schoenocaulon officinale) a member of the family Liliaceae, contain many seeds-derived alkaloidscevadine and its close relative veratridine. These alkaloids upon hydrolysis with alkaline yield cevacine (cevine) and protocevacine (cevadillin) which have been reported as the active principles of the extracts (Kupchan et al, 1953;Kanachanapoon, 2002;Greive, 2015). Though the later hydrolytic isolate is more toxic than the former (Greive, 2015), both act by disrupting neuron cell membrane bringing about reduction of nerve activity, symptomised by paralysis and death of susceptible organisms (Silva-Aguayo, 2015).…”