1306
YUOH-FONG CHI,YEP SHENG KAOAND Kou JEN CHANG [CONTRIBUTION FROM THE
NATIONAL RESEARCH INSTITUTE
OF CHEMISTRY,
Vol. 58
ACADEMIA SINICA]
The Alkaloids of Fritillaria Roylei. I. Isolation of Peiminel BY YUOH-FONG CHI, YEE SHENG KAOAND Kou JEN CHANG Previous contributions on the alkaloidal con- US, had the same melting point as C (peimine) ; tent of the plant Fritillaria Roylei (Pei-Mu) by but the results of our analyses of the free bases Fukuda2 and Chouas4have shown that it contains and its salts proved it to have the formula the following alkaloids : (A) verticin, C18H3302N C26H4303NI instead of Cl9HaoO2Nassigned to peior C19H3002N; (B) verticilin, CI9H3302N; (C) mine by Chou. Judging from the analytical data peimine, CI9H3002N; (D) peiminine, C18Ha802N; already known, we conclude this was probably the (E) fritimine, C38H&N2; and (F) fritillarin, same alkaloid as peimine, to which the present ClgH3302N. The properties of these alkaloids are authors have assigned a different formula. recorded in Table I. Experimental Part TABLE I Name
Peimine Peiminine Fritimine Verticin Yerticillin
I'ritillarin
M. p , O C Rotation Formula 0" ClgHU01N 223 -62.5" C I B H ~ ~ O135 ~N -50' CsgHezOsN 167 10.66" C&Ias02N 224-224.5 CieHasOiN ClsHS302N Sinters at 130, melts a t 148-150, resolidifies a t 157-159, decomposes a t 212213 CloHsaOlN 130-131
-
Pei-Mu source
Chekiang Chekiang Szechuen Japanese
Japanese Japanese
This interesting drug (Pei-Mu) finds wide application in medicine and is prescribed in fevers, coughs, dysuria, hemorrhages, deficiency of milk, threatened mammary abscess, lingering labor, rheumatism and diseases of the eye. This plant was identified as Fritillaria Roylei by Stuart6 or Fritillaria verticillata by Read and L k 6 The part of the plant used in medicine is the starchy corm of this liliaceous plant growing in different parts of China, especially in Chekiang and Szechuen. The material used for this investigation was a Chekiang variety known by the commercial name "Ta Pei," and was obtained from a local drug store or pharmacy. The pharmacological properties of peimine, peiminine and fritimine have been described by Chen. The alkaloid A, (verticin) recently isolated by (1) The authors wish to express their sincere thanks t o Mr. Yao Tseng Huang for his assistance in running the microanalyses recorded in this paper, and t o Professor Treat B . Johnson of the Sterling Chemistry Laboratory of Yale University for his aid in the arrangement of this paper for publication. (2) Fukuda, Science Reports, 7'dhoku I m f i . Cniz', J a p a n , 1, 18, 323 (1929). Also Chem. Zenlr., 1, 988 (1930). (3) Chou and Chen, Chinese J . Phrsiol., 6, 265 (1932). (4) Chou and Chen, ibid., 7, 41 (1933). ( 5 ) Stuart, Chinese Materia Medica, 178 (1911). (6) Read and l , i u ''F'liintnc hleilicinalis Sinensis," N o . 630, 1927, pp. A - I , -51,
Ninety-eight kilograms of the starch corms of Fritillaria Roylei, known under the commercial name "Ta Pei" was powdered, and percolated with 95% alcohol. When the solvent had been removed from the alcoholic extract under diminished pressure a t 4045", the residue was dissolved in 2% hydrochloric acid, and the solution filtered. The crude alkaloid was then liberated from the acid extract with sodium carbonate, and extracted with ether and then with chloroform. After distilling the solvent from the ethereal solution, the ether-soluble alkaloid weighed 48 g., which represented about 0.05% of the total quantity of the crude drug. This crude alkaloid dissolved in benzene, to which some petroleum ether was added just to turbidity, whereupon peimine separated as an amorphous powder. It was then purified by recrystallization from an alcohol-petroleum ether mixture, from which peimine separated in needles, melting a t 223-224'. In some cases, it was better to convert the ether-soluble alkaloids, after solution in dry ether, into their hydrochlorides by passing in dry hydrogen chloride. The mixed hydrochlorides were then separated into peimine hydrochloride and peiminine hydrochloride (to be described in our next paper) by fractional crystallization from an alcohol-ether mixture. Pure peimine was recovered from its hydrochloride by action of sodium carbonate. It was recrystallized from a mixture of alcohol-petroleum ether, and separated in needles melting a t 224". The yield of pure peimine was 3 g. For analysis, the alkaloid was dried over phosphorus pentoxide at 80" in a vacuum, [cY]"D 0". The hydrochloride and hydrobromide of peimine were prepared by dissolving in each case 100 mg. of the pure alkaloid in ether, passing in hydrogen chloride or bromide and recrystallizing from an alcohol-ether mixture. The acid sulfate was prepared in similar fashion except that dilute sulfuric acid was employed. The different products were dried for analysis over phosphorus pentoxide at 80" in a vacuum. The platinichloride and aurichloride were prepared by precipitation in aqueous solution. The former salt was recrystallized from water and the latter from dilute hydrochloric acid. The products were dried for analysis over phosphorus pentoxide at 110" in a vacuum. The results of analyses of the alkaloid and its different salts are rrcorded in Tahle 11.
TABW
Compound
M. p,, "C. Formula
1307
NOTES
July, 1936:
' Calcd.
Peimim (P) Hydrwhloride 224 295, dec. C*sH+aOaN P.HC1 74.75 68.74 74.66' 69.07, 68.77
Carbon, %
i
Nitrogen, % '
3.35 { Calcd. F o ~ d " ' ~3.56e
%
{ E d
Foundg'*
11
Hydrobromide 293.5-294 P.HBr 62.61 62.92, 62.88, 63.13'
Acid P@ipchlsAurichloaulf&e ride ride 278-280 233-235, dec. 164-165 P'H2SOI Pz'HaPtCls P'HAuC14 60.53 60.28, 60.27
2.81 2.72" Br
{ ~ ~ ' ~ ~15.45. 15.68
15.36
Au
( 2 6 03 24.9 125.09
{
Molecular weight determination (Rast); 0 288 rng. in 3 520 mg. camphor. AT, 9 2'. 0 268 mg in 3 810 mg.camphor; AT, 7 7'. Cakd. for C,F&O~N, 417.3. Found; 336," 365.2 Analyses made by a Analyses made by Dr Ing. A. Schoeller, Toelzestrasse 19, Berlin-hhmargendorf, Gemany. Average: 74.75, 74.85," 74 67," 74 76, 74 58,* 74 :j9,b Dr. Carl Tiedcke, Bismarckstrasse, Hamburg 18, Germany. 74 63.* Average: 10.30, 10.15, 10.49," 10.54," 10.43,b1D.53,b10.51.b Average: 3.52, 3.60, 3 77, 3.38," 1.36," 3.72.b
Summary Peimine, melting a t 2240J has been obtained in a more pure condition. Its formula is C2eH&NJ instead of C19H&N, which was assigned t o it by
Chou. The present fgrmula 1s substrantiated by the results of analysis of several salts; namely, the hydrochloride, bromide, wid sulfate, platinichloride aurichlo&e.
sHANGHAI, cHrNA
RECEIVED MAY7, 1936
NOTES veloped for mezpuring the heat of the reaction.' Frequently] however, it is desirable to analyze with a precision of abnut 1% + dilute solution of a free radical which will not absorb more than The apparatus illustrated in the figwe is de- about 1 cc. of gxygen. The &tails of breaking signed to measure the absorption d small amounts the capsule and measuring the absorption of of gas by solu$ions contained in sealed glms oxygen together with typical experimental results capsules. The apparatus allows one to break and are given in the follovping paragraphs. empty the capsule, measure the amount of The manipulation of the apparatus will be oxygen absorbed and make a correctjlon for the evident from the figure and the following deamount of oxygen dissolved in the solvent. The scription. "A" is a stopcock through which the sample is contained in a capsule "G" and the apparatus may be evacuated after the capsule oxygen to be introduced is measured in a capillary contaieing the solution of the free radical has been by means of the scale "3,"a small slug of mercury placed i i ~the apparatus. ''€3" is a scale placed in tke capillary serving to confine the gas. behind the capilbry {diameter 4 mm.3 in order The particular problem which necessitated the that the volume d oxygen introduced into the construction of this apparatus was the determina- absorption bulb may be accurately measured. tion of the purity of small quantities d organic "C'' is a three-way stopcock which connects the free radicals by measuring the quantity of oxygen capillary tube to the supply of oxygen and to the absorbed. Samples of a half gram or larger may (1) Ilent, Cuthbertson, Dorfman and Leary, 'THIS J O U R N A L , 88, conveniently be studied in the apparatus de- Mb (19:3@), Bent and CuthLertsori,{lrgd, 88, l i 0 (1936).
An Apparatus for the Determination of the Absorption of Small Quantities of Gas by Solutfons BY H. E. BENT,Pi.F. GWSHAMAND N. B. YEEVIL
