The Alkaloids of Coptis Trifolia.
(These experiments were carried on in the laboratory of Professor J. U. Lloyd, upon authentic specimens furnished by him. We take this opportunity to thank him for the attention shown us.)
BY JOHN J. SCHULTZ.
A Thesis Presented to the Cincinnati College of Pharmacy, Session 1883-84,
To find the proportion of alkaloids in Coptis trifolia, five pounds of carefully selected coptis, in moderately coarse powder, were moistened with officinal alcohol and packed firmly in a properly prepared cylindrical percolator. Officinal alcohol was then added in successive portions of two gallons each. The last portion was acidulated with four ounces of acetic acid. After each addition, maceration was conducted for twenty-four hours, and percolation was continued until the percolate finally passed almost colorless and devoid of any bitter taste.
Five gallons and five pints of percolate of a yellowish brown color and decidedly bitter taste were obtained. The dregs after having been removed from the percolator and dried at a temperature of 110°F., weighed four pounds and eight ounces, showing a loss of eight ounces.
To four and one-half pints of this percolate, representing eight ounces of drug, an excess of sulphuric acid was added and the mixture set aside in a cool place.
To one pint and two ounces of percolate, representing two ounces of drug, an excess of hydrochloric acid was added and the mixture set aside with the foregoing.
After standing forty-eight hours a precipitate had formed in each, that of the sulphuric acid being light yellow, while that of the hydrochloric acid was yellowish brown.
The supernatant liquids in each case were bitter and retained a decided yellow color, characteristic of berberine, showing that the precipitation of the berberine had been incomplete.
Two pints and four ounces of the original percolate, representing four ounces of drug, were then subjected to distillation, until the residue was of a syrupy consistence. The retort was then rinsed with eight ounces of water, the result placed in an evaporating dish, and the last traces of alcohol vaporized. A dark greenish fixed oil and a lighter colored resin began to separate as the alcohol evaporated, and these were completely precipitated by allowing the liquid to stand in a cool place for twenty-four hours. The contents of the dish were then thoroughly agitated with water and filtered. The filtrate was now evaporated to a syrupy consistence and eight ounces of alcohol added. This was divided into two equal portions, and one was strongly acidulated with sulphuric, the other with hydrochloric acid, and both set aside in a cool place.
After standing twenty-four hours, the portion acidulated with sulphuric acid had formed a considerable amount of a brownish yellow precipitate, but the supernatant liquid was still bitter and retained its yellow color. The portion acidulated with hydrochloric acid showed only a slight cloudiness, and did not precipitate even after standing for two weeks.
The foregoing processes are the ones usually employed for the separation of berberine, and neither, in these instances, gave a satisfactory result.
Through the courtesy of Professor J. U. Lloyd, we were enabled next to employ his scheme for the determination of berberine, as stated in the manuscript of his work upon "Drugs and Medicines of North America," and which is based upon the insolubility of picrate of berberine in most menstruums.
The first step was to separate the second alkaloid, discovered by Mr. E. Z. Gross, as follows: Of the remainder of the percolate, four gallons and one pint, representing four pounds of drug, were subjected to distillation, and the oil and resin separated in the manner heretofore described. To the resulting nitrate, officinal water of ammonia was added until slightly in excess. This produced a dark brown flocculent precipitate, which was collected on a filter and thoroughly washed with water. The filtrate, after having been slightly acidulated with sulphuric acid, and allowed to stand for several hours, was brought to an alkaline reaction by the addition of water of ammonia, when a second precipitation took place similar in appearance to the first. This and the foregoing precipitate after having been mixed and dried spontaneously, was treated with successive portions of chloroform. The chloroform was then distilled, and the residue exhausted with dilute sulphuric acid. The resulting solution when filtered and made alkaline by addition of ammonia water, gave a precipitate which when dried spontaneously, weighed 3.42 grains.
A portion of this precipitate when dissolved in water acidulated with acetic acid, gave precipitates with the following reagents for alkaloids: Platinic chloride, molybdate of ammonium, solution of iodine in iodide of potassium, and test solution of iodide of mercury and potassium.
A chloroformic solution of the remainder of this precipitate when evaporated on a slide formed microscopic crystals, but the quantity obtained was too small to admit of further investigation. (This was the second alkaloid as found by Mr. Gross.)
To a portion of the filtrate, from the foregoing precipitates, solution of carbonate of sodium was added without producing any precipitate, and it was positively shown that there was no more of this second alkaloid present.
To the entire filtrate and washings thus obtained from the second alkaloid, and which were of alkaline reaction, a solution of carbazotate of ammonium was now added. This produced a bulky yellow precipitate of carbazotate of berberine, which when collected on a filter and dried spontaneously, weighed 292.8 grains, corresponding to 228.03 grains of sulphate of berberine.
In order to test the filtrate for any remaining alkaloids, a portion was evaporated nearly to dryness on a water bath, and agitated successively with ether, chloroform, benzol and carbon disulphide.
The several solutions were evaporated, the residue dissolved in water and portions of it separately tested with test solution of iodide of mercury and potassium, molybdate of ammonium, and chloride of platinum, without producing any precipitate, thus showing the previous complete separation of all the alkaloids.
Recapitulation.—The foregoing experiments show, that Coptis trifolia yields to officinal alcohol, slightly acidulated with acetic acid, 10 per cent. of its weight of extractive matter. That it contains two alkaloids, as previously shown by the investigations of Mr. E. Z. Gross ("Am. Jour. Pharm.," 1873). That the berberine of Coptis trifolia is only partially separated by the processes usually employed for the determination of berberine. That it contains of berberine an amount equivalent to 0.8 per cent. of sulphate of berberine, or 57 grains of sulphate of berberine to the avoirdupois pound. That the amount of the second alkaloid is very small, 0.012 per cent., or only 0.855 grain to the avoirdupois pound having been obtained.