42 1

XLVII.-!l%e Alkaloids of the Verutrums. Par t 111. The Alkaloids of reratrum Viride.

By C. R. ALDER WRIGHT, D.Sc. (Lond.), Lecturer on Chemistry in St. Mary’s Hospital Medical School.

Ix order to see whether the alkalo’ids contained in Veratrum viride are in any may related to those isolated as described in Part I1 from V. album, and in particular whether the so-called “ viridine ” of Bul- lock is identical o r not with jerrine, about 18 kilos. (414 lbs.) of V. viride root (obtained from Messrs. Ho,qkins and Williams) were percolated with alcohol containing about 130 grams of tartaric acid (about 0.7 per cent. of the weight of the roots), about 15 gallons of alcohol being used, and the percolate from one batch of about 3 or 4 lbs. being used to percolate another batch, and so on in series of four batches, like the lixiviation of black-ash in the alkali manufac- ture, &c.

The percolate was distilled to a sinall bulk, treated with water to separate most of the resin, shaken with ether to remove the remainder, and then alkalised with a slight excess of caustic soda and shaken repeatedly with about an equal bulk of ether. Just as with V. album, R perceptible amouut of alkaloid remained undissolved even after six treatments with ether; this was collected on a calico filter and ex- amined, when it appeared to be essentially one alkalojid, apparently the pseudojervine described in Part 11. The ethereal extract was shaken with tartaric acid solution, and the acid tartrates thus obtained treated with a little caustic soda and fresh ether ; the great majority of the precipitate thus obtaiued dissolved in the ether, yielding a solution from which crystals separated on standing, apparently con- sisting almost entirely of jervine, identical with that from V. albuin ; the mother-liquors of these crystals dried up to a varnish resembling the so-called “ vemtria,” similarly obtaicable from I? aZlwx, and like it, possessing all the sternutatory powers of the root ; it differed from it however in this respect, that’ whilst the product from 7. album yielded veratric acid in small quantity on saponification, and appeared to be a mixture of veratrine (of Couerbe, Part I> with it large excess of veratralbine, an inert base probably indicated by the formula C,,H,,NO,, the product from V. &rick yielded o n saponification cevadic acid,* and appeared to be almost wholly cevadine (the “ veratria ” of Merck, and of Schmidt and Koppen). Only a minute quantity of alka- loid, too, remained undissolved by the ether on this secoud treatment ;

* Doubtless identical with the methjl-crotonic acid of Frankland and Duppa (Part I), and with the tiglic acid of Geuther and others from croton oil.

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4-22 WRIGI-IT ON THE ALKALOIDS OF THE VERATRUIZIS.

and this appeared to consist almost entirely of pseudojervbe with a little rubijervine ; whereas the :orresponding fraction obtained with V. album roots mainly consisted of the amorphous alkalo'id, C2,H,,N05, sparingly soluble in ether (veratralbine) .

The total amount of alkaloidal matter obtained from I? viride was only about one-fifth of that from V. album, the proportions of the different alkaloids present being about as follows per kilo. of roots :-

V. album. Jervine . . . . . . . Pseudojervine . . 0.4 ,, Rubijervine . . . . 0.25 ,, Veratralbine.. . . 2.2 ,, Veratrine ...... 0.05 ,, Cevadine . . . . . .

1.3 gram.

apparently absent.

4.20

The following numbers and other data

V. viride. 0.2 gram. 0.15 ,, 0.02. ,, not more than traces. trace: less than 0.004. 0.43 gram.

0-80 -

were obtained by the further examination of the different fractions isolated as just de- scribed.

1st Fraction. Base left undissolved by ether after six treatments therewith of the original extract freed from resin and alkalised.

The slightly brown flocculent semicrystalline mass left undissolved hy the ether was dissolved in dilute sulphuric acid, which did not leave any iiisoluble jervine sulphate ; the solution was precipitated by caustic soda, filter-pumped, and the residue crystallised from alcohol ; snow-white anhydrous crystals thus separated agreeing in every respect with pseudojervine from V. aZbzim. To purify these further, t,hey were rubbed with a slight excesi of dilute hydrochloric acid, and the resulting magma filter-pumped and washed. The filtrate con- tained besides paeudojervine a minute quantity of rubijervine ; a t least, on precipitating with soda, filtering, and washing, a small quantity of base was obtained, giving with sulphuric acid a colour reaction pre- cisely like that yielded by a mixture of pseudojervine (giving an emerald-green), and rubijervine (giving a blood-red-crimson-red) ; the qustntity, however, was too small to enable any pure rubijervine to be separated.

The magma of hydrochloride crystals, after draining and filter- pumping, was boiled with alcohol and sodium carbonate : the filtrate deposited snow-white crystals, anhydrous when air-dry, giving the same reaction with sulphuric acid as pseudojervine, and melting at 299" (corrected). The following numbers were obtained by Mr. A. E. Menke on combustion: 0.2575 gram gave 0.6305 GO, and 0.1970 HZO.

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WRIGHT ON ~ r n ALKALOIDS OF THE YERATRUMS. 423

Calculated. Found. c,, ........ 348 67.31 6 6 . X H43 ........ 43 8.32 8-50 N 2.71 - ........ 14 0, 21.66 - .... . . . . 112

Like the pseudojervine from V. aZbuna, the gold salt of this base was

0.7880 gram of gold salt dried at 100" gave 0.1770 Au .............................. = 22.46 per cent.

not distinctly crys t a1 lin e.

Calculated for C29H43NOi, HCI, AuCl, = 22.89 ,, The alcoholic mother-liquors of the first crystals obtained before

conversion into hydrochloride dried up t o a mixture of cr-ptalline pseudojervine and a brownish amorphous alkalo'idal body yielding a,

dirty red coloration with sulphuric acid ; the quantity of this was too small for separation from the pseudojervine mixed with it ; presumably it was verat,ralbine, the amorphous base sparingly soluble in ether obtained from V. album, and approximating in composition to C,H,,NO,.

2nd Fraction. Base left undissolved by ether on treatment of the crude tartrates (obtained by shaking the first ethereal extract with tartaric acid) with soda and ether. So small a quantityof this fraction was obtained, that its quantitative examination was impracticable : i t contained no more than traces of amorphous a1kaloi.d ; after crystal- lisation from alcohol, it wholly dissolved in dilute sulphuric acid, showing the absence of jervine ; on treatment with hydrochloric acid, it gave an almost insoluble hydrochloride with a little of a much more soluble salt : the former on boiling with alcohol and sodium carbonate gave a little crystallised psendojervine melting a t 298", and giving a clear green coloration with sulphuric acid; the latter furnishcd a,

crystallised base, giving with sulphuric acid a coloration like that of pseudojervine containing a small qiwntity of rubijervine ; whence doubtless the fraction consisted of these two bases, the latter present only in small quantity.

3rd Ei.actim. Crystals deposited from the ethereal solution of bases derived from the crude tartrate solution of bases (obtained from the first ethereal extract by shaking with tartaric acid).

These cryst,& appeared to be jerrine free from any appreciable quan- tity of pseudojervine or rubijervine : they yielded with dilute sul- phuric acid a salt almost wholly insoluble in cold water, and almost insoluble in boiling water after freeing from excess of acid by mashing. From the filtrates, nothing but jervine was obtained by precipitation

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4-24 WRIGHT ON THE ALKALOIDS O F THE VERATRUMS.

with soda, and onIy a fern centigrams of that. Theinsoluble sulphate, after. boiling with water, was drained, and then boiled with alcohol and sodium carbonate : crysteals were obtained on cooling precisely resembling jervine from V. album, giving the same colour reaction with snlphuric acid, and melting a t 239" (corrected). The following numbers were obtained :-

0.6470 gram of air-dry crystals lost a t 100" 0.049 gram = 7.58 per

The specimens from V. albuin lost from 5.19 to 8.20 per cent., the

cent.

formula, C26H37X03, 2H20, requiring 8.05 per cent.

0.1415 gram of anhydrous base gave 0.3905 %Oa and 0.1165 HZO. 0.1380 77 7 7 7 ) 0.3800 ,, 0-1140 ,,

Calculated. Found. Czij ........ 312 75.91 75.26 75.10 Ha, ........ 37 9.00 9.14 9-18 N .......... 14 3'41 0, .......... 48 11.68

- - - --

C2,H3,N03 . . 411 100~00

0,4775 gram of gold salt dried in the air and then over sulphuric asid several days till absolutely constant in weight, lost at 100" 0.0100 gram = 2.10 per cent.

Calculated for C,,H,,NO,, HCI, AuC13, H,O = 2.34 per cent. 0.4675 gram of dried salt gave 0.1200 Au = 25.67 per cent.

Calculated for C,H,NO,, HCI, AuCl, = 26.13 ,, 4th Fraction. Amorphous bases most readily soluble in ether (mother-

liquors of 3rd fraction), so-called " veratria" or '' veratroidia." The amorphous base, C,HJ?O, (veratralbine), sparingly soluble in ether, found to constitute altogether about half of the alkalo'ids extracted from Veratrum album roots, not having been found to any considerable extent in fraction 2, i t would seem probable that the V. viride roots examined did not contain any considerable quantity of this substance : whence the alkaloids most soluble in ether might be anticipated to consist almost wholly of the s ternutatory saponifiable alkaloid found in the V. album roots in small quantity. This appears to be the case, with the difference, however, that whilst the sternutatorg constituent of 7. album was apparently veratrine, C,,H,,NO,, (since verntric acid and no appreciable amount of ceradic acid was formed on saponifica- tion), the sternutatory constituent of V . ci)*ide was essentially cevadine, C,H,,NO,, only traces of veratric acid being formed on saponification, whilst much cevadic acid was thereby produced,

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WRIGHT ON THE ALKALOIDS O F THE VERhTRUblS. 425

The following numbers were obtained :-

0.2645 gram gave 0.6310 CO, and 0.1985 H,O.

Calculated. Found. c,, ............ 384 64.9 7 65.06 HAg ............ 49 8-29 8.34 N .............. 14 0, ............ 144 24.3 7

2.37 - -

C,,H,gNO, ...... 591 100~00

0.3760 gram of gold salt dried a t 100" gave 0.0805 Au = 21.41 per cent.

Calculated for C,2H,gNOg, HCl, AuCI, = 21.08 per cent.

On saponification with alcoholic potash for 24 hours, evaporation 2nd distillation of the residue with dilute sulphuric acid, an acid dis- tillate was obtained containing an acid apparently identical with cevadic acid. The quantity obtained was too small for the isolation of pure crjstallised ceradic acid, but it agreed therewith in all its qualitative reactions. 2-380 grams thus yielded acid sufficient to neu- tralise 5 C.C. of normal alkali solution. The quantity corresponding t'o 2.380 grams of pure cevadine would be 4.03 C.C. were only cevadic acid formed ; but as the experiments described in Part I showed that cevadic acid when thus liberated is partially decomposed forming acetic and propionic acids, an excess of volatile acid would necessarily be formed. The residue left on distilling off the volatile acid was shaken with ether, which extracted 0.041 gram = 1.7 per cent. of substance, chiefly amorphous resinous matter. A trace of veratric acid, however, appeared to be also present, as a minute quantity of a crystalline acid, yielding protocatechuic acid on fusion with caustic potash a t 250", was also left by the ether on evaporation ; a t most, the amount of verd- trine thus probably present could not have amounted to 1 per cent. of the amorphous alkaloi'dal mass examined, or less than 0.004 gram of veratrine per kilo. of root. T'he ceradic acid solution, distilled off and neutralised w;th sodium carbonate, was evaporated to a small bulk and treated with sulphuric acid and ether, and the ethereal solution allowed to evaporate spontaneously ; the oily imperfectly pure cevadic acid thus obtaiued smelt precisely like that from cevadine ; it was readily soluble in water on agitation therewith, and afber neutralisation with ammonia, precipitated silver nitrate, ferric chloride, and copper nitrate. After exposure to the air for some hours to remove as far as possible the small quantities of acetic and propionic acid produced by its partial decomposition during formation, it was converted into barium salt by addition of baryta-water and treatment with carbon dioxide to remove

VOL, XYXV. 2 6

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426 WRIGHT OX THE ALKALOIDS OF THE VERATRUMS.

excess; the barium salt solution dried up a t 100" to an amorphous salt, of which 0.2375 gram gave -1645 BaS04.

Calculated for Ba(C5H,02)2 = 40.89 per cent. All attempts t o obtain crystallised cevadine from the amorphous

sternutatory mass proved fruitless ; but as the total quantity operated on did not amount to many grams, and as this doubtless contained small quantities of other substances, the isolation of cevadine in crystals could hardly have been expected, great difficulty being experienced, as stsated in Part I, in obtaining more than a small fraction of the cevadine present in a mixture of alkaloids in a crjstallised state, even wheii several ounces of mixture are employed. The melting point of the amorphous mixture was found to be about 140" (cevadine melts at 205-2.36" when pure). With sulphu~ic acid it gave the same coiour reaction as cevadine, utterly different from that of jervine. No crys- fallisable salts appeared to be formed with mineral acids, the solutions drying up to varnishes.

From the experiments detailed in the preceding three parts of these researches, i t results that the Sabadilla seeds examined (Part' I) con- tained the following alkalo'ids :-

(1,) Cevadine (veratririe of Merck), C,,R,,NO,, yielding cevatdic, inethylcrotonic, or tiglic acid on saponification.

(2.) Veratrine (of Couerbe), C37H53NOll, yielding veratric (dimethF1- protocat8echuic) acid on saponification.

(3.) Cevadilline (in small quantity), C,IH,3N08. The TT. aZbunL roots examined (Part 11) contained neither cevadine

nor cevadilline, but small quantities of reratrine, to which thcir sternu- tatory action was due. (4.) Jervine (of Simon), C26H37N03 ; not saponifiable ; crystalli-

sable. ( 5 . ) Pseudojervine, CZ,H,,NO, ; no t saponifiable ; crystallisable. (6.) Rubijervine (in small quantity), C2sH,,N0, ; not saponifrable ;

cry stallisable. ('7.) Veratralbine, approximately Cz8HA3N05 ; not saponifiable ;

amorphous. The V. uiride roots examined (Part 111) contained a trace only of

veratrine and veratralbine, and only a minute quantity of rubi jervine, the alkaloids present being essentially jervine, pseudojervine, and caevadine, cevadilline being absent. The sternutatory action was here rrainly due to cevadine.

Ba = 40.72 per cent.

In addit)ion, they contained four other bases.

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