A review of gaultherin, the glucoside from Betula lenta, L.
By Frank X. Moerk, Ph.G.At the Pharmaceutical meeting held in the Philadelphia College of Pharmacy, December 4, 1843, paper was read by William Procter, Jr., entitled "Observations on the Volatile Oil of Betula Lenta, and on Gaultherin, a Substance Which, by Its Decomposition, Yields That Oil." The important points of that paper may be briefly reviewed as follows, using, as far as possible, the exact words of the writer: (i) as establishing the identity of volatile oil of Betula lenta with the oil of gaultheria, which had shortly before been proved to be methyl salicylate by M. Cahours; (2) establishing the existence of a peculiar principle in the bark of Betula lenta, which bears the same kind of relation to the oil of gaultheria or Betula lenta that amygdalin bears to the oil of bitter almond, and which was called gaultherin, as it gave rise to the oil of gaultheria by its decomposition; the term betulin was admitted to be more appropriate, but had already been applied to another substance; (3) the existence in the bark of Betula lenta, associated with gaultherin, of a substance enjoying the property of reacting with the latter so as to produce the volatile oil, and which is analogous in its mode of operation to synaptase or emulsin. The constituents of the bark of Betula lenta were given as tannin, gum, saccharine matter, resin in considerable quantity, gaultherin, fixed oil soluble in alcohol, etc. The dry bark does not possess the odor peculiar to the volatile oil, but the latter is only developed by contact with water, recalling the analogous behavior of wild cherry bark. The powdered bark, exhausted by maceration and displacement with cold 95 per cent. alcohol, no longer gives the odor of the oil when moistened with water; the alcoholic solution, evaporated to an extract and mixed with a part of the exhausted bark and water, immediately developed the odor, and by distillation yielded a liquid which gave all of the tests for the oil of Betula lenta.
The leaves of Gaultheria procumbens, after drying, did not yield the same principle; the leaves, when long kept, lose their odor, and mixture with water does not revive it as with Betula lenta; hence, it would seem that the methyl salicylate is an immediate product in the Gaultheria procumbens, whilst in the Betula lenta it is secondary. To purify this principle, gaultherin, the alcoholic extract of the bark is treated with water, which leaves the resin and fixed oil; the dark red liquid so obtained, containing tannin, extractive and saccharine matter, is then treated with an excess of lead hydrate until these substances are separated and the transparent, nearly colorless liquid obtained by filtration is carefully evaporated. A transparent, gummy mass results, which almost wholly dissolves in 97 per cent. alcohol; the alcoholic solution by spontaneous evaporation yields a syrupy, almost colorless product, which does not crystallize after standing several weeks. In this state it is evidently associated with some substance that prevents its crystallization. The syrupy liquid was agitated with several times its bulk of ether, but the former separated from the mixture unchanged. The difficulty of combining gaultherin with other bodies opposes a barrier to its examination.
As thus obtained, gaultherin has little if any odor and a slightly bitter taste; heated carefully on a glass plate until all the moisture has evaporated, it remains as an easily pulverizable, varnish-like layer, which may be heated to 300° F. without change; at 400° F. it is decomposed, oil of gaultheria being among the products. Distillation with diluted hydrochloric and sulphuric acids gave rise to the volatile oil; diluted nitric acid gave minute yellow crystals, similar to those obtainable from the oil.
The fixed alkalies and alkaline hydrates wholly destroy the power of generating the volatile oil, and convert gaultherin into an acid (gaultheric acid), which remains combined with the base. Ammonia has but slight action upon gaultherin, as, after boiling, it still is capable of producing the volatile oil by reaction with the residue of the bark.
Gaultherin boiled with lead hydrate and water is but slightly decomposed, yielding a filtrate having an alkaline reaction and containing lead; by the cautious addition of sulphuric acid and filtering off the lead sulphate, there is obtained an acid solution which contains no sulphuric acid.
Gaultherin in aqueous solution, made alkaline with ammonia, is precipitated by lead subacetate, but appears to be converted into gaultheric acid or otherwise decomposed, as neither the liquid filtered from the precipitate nor that obtained by decomposing the precipitate with dilute sulphuric acid would yield the volatile oil when mixed with the residue of the bark. Gaultheric acid is obtained by dissolving gaultherin in baryta water, boiling the solution for a short time, and afterward passing a current of carbonic acid gas through the liquid until all free baryta is removed, and then filtering. A neutral solution of gaultherate of barium is obtained, from which the free acid may be isolated by the cautious addition of dilute sulphuric acid, as long as a precipitate is produced. The filtered liquid is strongly acid and does not precipitate baryta water; by evaporation it dries into a gum-like mass. In this form it is impure. By boiling it with lead carbonate until saturated, filtering and precipitating the lead with hydrogen sulphide, a solution is obtained containing the acid in a much purer state, which, by evaporation, yields it in a nearly colorless mass with some evidence of crystallization. Gaultheric acid is soluble in water and alcohol, but is only slightly taken up by ether. It saturates bases, forming neutral salts which do not crystallize. By distilling it with dilute sulphuric acid, oil of gaultheria is obtained, and nitric acid appears to act on it like gaultherin.
The substance existing in the residue of the bark, after exhaustion by alcohol, and which reacts with gaultherin to produce the volatile oil, has not been isolated. It is insoluble in water, as by long maceration in that fluid it is not removed or changed. The temperature of ebullition, as well as maceration in solution of potassa sp. gr. 1.05, destroys its power of acting upon gaultherin. The impossibility of finding a menstruum capable of dissolving this principle, has prevented a further examination of its properties.
It will be interesting to know the ultimate composition of this principle and the relation it bears to gaultheric acid and methyl salicylate; before that can be accomplished, the necessity of obtaining it in a pure state is imperative. It is hoped that the attention of chemists will be attracted to these principles, and their character more fully developed.
Just about fifty years have elapsed since the publication of the above experiments without any further investigation being recorded. In Archiv der Pharmacie, 1894, page 437, there is to be found the second publication bearing upon this subject, by Dr. A. Schneegans and J. E. Gerock. These writers have taken as their field of labor the separation and properties of glucosides which, by their decomposition, yield volatile oils. Their first paper bearing upon the volatile oil of Spiraea ulmaria was published about two years ago. The results of this investigation, while not as successful as anticipated, disclosed that several glucosides were present, which, by their decomposition, yielded salicyl-aldehyde, as well as methyl salicylate, but the quantities of these glucosides which are present was very small, so that their preparation in a state of purity was not successful.
Turning their attention next to the glucoside yielding methyl salicylate which appeared to offer more promising results, the bark of Betula lenta was taken for investigation. Preliminary experiments established the absence of preformed volatile oil; the 94 per cent. alcoholic tincture, always possessing the odor of wintergreen, indicated the unexpected decomposition of the glucoside in strong alcoholic solution; to prevent this decomposition the bark was extracted with lead acetate (15 per cent. of the weight of the bark) in strong alcoholic solution, whereby the ferment is rendered inactive. Such a tincture possesses no odor of wintergreen. After precipitating the lead with hydrogen sulphide, the liquid is concentrated by distilling off the alcohol; the brown syrupy residue is taken up in absolute alcohol, filtered from the insoluble substances, and the filtrate mixed with several volumes of ether, when a voluminous white precipitate is produced, which agglutinates to a yellow, plastic mass. This, redissolved in alcohol and allowed to evaporate spontaneously, forms a thick liquid, in which are slowly formed starshaped groups of short, prismatic crystals. The crystals, separated by suction from the mother-liquor (this by exposure for several months to low temperature did not separate any additional crystals; it consisted almost entirely of a reducing sugar, and contained but traces of gaultherin, as distillation with dilute acids failed to give appreciable quantities of the oil), and recrystallized several times from alcohol after digesting with animal charcoal, were obtained as colorless, crystalline needles. The name gaultherin is retained for the same reasons given by Procter.
Gaultherin is quite, although in the crystallized condition only slowly, soluble in water; also soluble in alcohol and concentrated acetic acid without decomposition; ether, chloroform, aceton, benzol, do not dissolve it. Concentrated sulphuric acid dissolves it, with a pale rose color, changing quickly to brown and black. It does not melt without decomposition; a little above 100° C. the odor of gaultheria becomes perceptible, and at 120° C. it commences to become brown. The freshly prepared aqueous solution is not colored by ferric salts even after boiling. Fehling's solution is not reduced in the cold, but quickly upon boiling. Heated with small quantities of mineral acids, the odor of wintergreen is recognizable, and the fluid becomes milky, and, if sufficiently concentrated, deposits heavy, oily drops; the solution then quickly reduces Fehling's solution.
Gaultherin, in aqueous solution, is laevogyre; it possesses a purely bitter taste, therefore is not decomposed by the ferments of the saliva; it is not decomposed by emulsin or diastase. Decomposed by dilute mineral acids, it yields only two products, sugar and methyl salicylate. Moist gaultherin is slowly decomposed, as is shown by the faint odor of wintergreen which such specimens show after a few days; the aqueous solution, heated in a closed tube to 130°-140° C, gives the above-mentioned two decomposition products.
The glucoside crystallizes with a molecule of water, which is only in part given off if kept over sulphuric acid or dried at ordinary temperature or with moderate heating; drying at a somewhat higher temperature brings about its decomposition, so that combustions made with the crystals dried under different conditions show a variation of as much as 2 per cent. in the amount of carbon. After ascertaining the cause of these variable figures, two combustions were made, giving the following composition:
|I.||II.||Calculated for C14H18O8+H2O|
Procter's preparation in all probability consisted chiefly of sugar; the formation of gaultheric acid (which see in the previous part), by boiling with baryta water, as stated by Procter, was repeated with the crystallized gaultherin, but with very different results. Baryta water, in the cold, will decompose gaultherin after a short time; heated to the boiling point the glucoside is decomposed with the saponification of the methyl salicylate so that the solution contains methyl alcohol, barium salicylate and sugar; what was called gaultheric acid, therefore, is a mixture of sugar and salicylic acid, and all of the properties ascribed by Procter to this acid are due this mixture, save one, which is not explainable, namely, the formation of oil of wintergreen by distilling the so-called gaultheric acid with dilute sulphuric acid. If the proof of this consisted in testing the distillate with a ferric salt, instead of actually observing the oil, even this is explainable, as salicylic acid will volatilize with the steam.
Without attempting the isolation of the ferment, which brings about the decomposition of the gaultherin, the statement of Procter, that the ferment is insoluble in water, is discredited, on the ground that moistening the powdered bark develops almost instantly the odor of wintergreen. Attention is called to the development of the wintergreen odor in the alcoholic tinctures, and that the indicated decomposition of the gaultherin continues during the evaporation of the solutions. A complete decomposition of the glucoside during the evaporation was, however, never observed. To prevent this decomposition various experiments were made to render the ferment inactive; drying the powder at 110° C. for some hours, and the employment of mercuric chloride solution, were without effect; adding the powdered bark to boiling water somewhat interfered with the ferment, as decidedly smaller yields of volatile oil were then noticed; the use of lead acetate proved to be the simplest and most reliable method of preventing the decomposition of gaultherin by the ferment. (This, possibly, is then the explanation of the remarkable behavior of gaultherin noticed by Procter when he added lead sub-acetate to an ammoniacal solution of gaultherin and tried the effect of the original filtrate and of the filtrate resulting from the decomposition of the precipitate with dilute sulphuric acid upon some of the exhau.sted bark without getting the odor of wintergreen from either solution.) [See previous part of this paper.]
An extended chemical investigation of gaultherin was intended, but was frustrated by the disappointingly small yield of gaultherin from a second lot of bark imported especially for this work; the cause of this small yield cannot be positively stated, as it may be due to the time of collecting the bark or to a decomposition of the greater portion of the glucoside by some unknown cause.