2406 EWINS: NARCISSINE: A N ALKALOID FROM THE BULB OFC1CXLV.-i~'c~ilcissi~?.r! : c i t b Alkcdoicl f m m the Bull, ofthe ConmmL Dafodil (Narcissies psewhara'ss.zcs).By ARTaun JAMZS &+-INS.IN 1878 a paper was published by Ringcr and Morshead ( J . P?ipiol.1, 437), entitled " On the physiological action of narcissia, analldoid obtained from the bulb of thc connuon daffodil (Sarcissrrspseuclonarcissua)." This work contained a detailed .account ofexperiments carried out on men and frogs with an alkaloid or withextr<acts cont,a.ining the alkaloid, which had been obta.ined byGorra,rd from the bulb of the common daffodil. From experimentscarried out with extracts obtained from bulbs in the resting &ageand from bulbs of t,he flowering p h t s , the authors concluded thatthe adion of the alkaloid prownt in t,he extracts from the resthgbulbs was similar to that of pilocarpine, whcreas that present inthe extracts from the bulbs of the flowering plants closely resembledatropine in action.The a.lka.loid obtained by Gerrard from bothextracts nevertheless a.ppearcd to be tlic same in general chemicalpropertiesTHE COMMON DAFFODIL (NARCISSUS PSEUDONARCISSUS). 2407I n view of these statements and of the fact that no reference to“narcissia” or to any alkaloid obtained from the bulbs of thedaffodil can be found in chemical literature, it appeared to be ofinterest to obtain the alkaloid in a pure state, in order that a moredetailed investigation of its chemical and physiological propertiesmight be made, more especially as the alkaloids which have beenobtained from monocotyledons are comparatively few in number.The bulbs of a cultivated variety of the daffodil (A7arciss?6Sprinceps), being more readily obtainable than the variety mentionedabove, were first employed in the investigation.From these bulbs,however, the extracts obtained from the resting or flowering bulbsgave only traces of alkaloidal reactions, and the isolation of thealkaloid was obviously hopeless. With t h e h l b s of the wild daffodil(Narcissus pseudonarcissus), much more satisfactory results wereobtained. From these a crystalline alkaloid was readily obtained.From the resting bulbs a yield of approximately 0.2 per cent. ofthe dried material, and from the flowering bulbs only about 0.1per cent., was obtained.The alkaloid, which, in accordance withmodern usage, it is suggested be called “narcissine,” rather than“ narcissia,” was the same in both cases.Narcissine has been found by analyses and molecular-weightdetermination to possess the formula Cl,H170,N;. The alkaloid ischaracterised by very great stability, and on that account) andowing to the small amount of material available (about 3 gramsonly), no light has been thrown on its probable constitution. Tlienitrogen present is tertiary, since nitrous acid is without action onthe alkaloid, and treatment with methyl iodide produced anamorphous product which was probably the methiodide of the base,but which could not be crystalljsed for analysis.The action ofhydriodic acid (Zeisel) showed the absence of methoxy-groups, buton very strongly heating, a very small amount of methyl iodidewas evolved, and the residue on suitable treatment yielded a solutionwhich gave a violet coloration with ferric chloride, the phenolicsubstance being extracted from its acid solution by ether. Theamount of substance so obtained was, however, extremely small, andfurther attempts to hydrolyse by means of acids yielded nocrystalline product.A ttemperatures up to 220° the alkaloid was only very slowly attacked,traces of alkaline vapour being evolved. Heating with the nakedflame for one and a-quarter hours was required in order to decomposecompletely about 0.7 gram of the alkaloid. The reaction productdissolved in water gave on addition of ferric chloride a violetcoloration, quickly passing to it dirty brown, with separation of a,Fusion with potassium hydroxide yielded no better results.7 s 2408 EWIN3: NARCISSINE: AN ALKALOID FROM THE BULB OFbrown, fiocculknt precipitate.This polyphenolic substance, again,could be extracted by ether from its acid solution, but on evaporatingoff the solvent only a very small quantity of a brown, amorphousproduct was obtained, and all attempts to obtain a crystallineproduct were fruitless.On account of the relatively large number of oxygen atomspresent in the molecule, it was thought possible that a carboxylgroup might be present, but attempted esterification showed theabsence of such grouping. For this reason and from the absence ofmethoxy-groups as shown by the Zeisel reaction, the formation ofa polyphenolic derivative such as has been described is very possiblydue to the presence in the molecule of a methylenedioxy-groupingand a phenolic bridge oxygen. The stability of the alkaloid wouldseem to support such a view, although there is, of course, no directevidence of such structure.Experiments with regard to the physiological action of thealkaloid were carried out in these laboratories by Dr.P. I?. Laidlaw,to whom I am indebted for the following account of its action.As tested on frogs and cats, the alkaloid showed no action in anyway similar to that of pilocarpine or of atropine. 0.125 Gram,given by mouth to a cat, caused nausea, vomiting, salivation, andpurgation.The salivation was not, however, similar to that producedby pilocarpine, since it could not be produced on the anaesthetisedanim a1 .EXPERIMENTAL.Preparation of the Alkuloid.Two thousand five hundred bulbs of the common daffodil(Narcissus pseudonarcissus), weighing approximately 4 kilos., weredried at a temperature of about 40°. The weight of the driedproduct was 1400 grams. The substance was finely ground andextracted for about six hours with hot alcohol (97 per cent.), a-ndthe alcoholic extract evaporated to about 200 C.C. To the darksyrupy, acid liquid was added an equal volume of water, and avery dark resinous precipitate which formed was collected. Thisprecipitate was re-suspended in a little very dilute acid, and againcollected after thoroughly shaking.The filtrate and washings werecombined, and the acid liquid extracted twice with about one-thirdof its volume of ether. The aqueous solution was then renderedalkaline by addition of sodium carbonate, when, after some time, aprecipitate formed, which consisted mainly of bunched prisms. Thecrystals were collected, and after recrystallisation from 90 per cent.alcohol were obtained as colourless, short, stout prisms, melting a t266-267O (bath at 250° at commencement of heating). The sub-stance was dried first in air, then in a vacuum over sulphuric acidTHE COMMOX DAFFODIL (NARCISSUS PSEUDONARCISSUS). 2409and finally at llOo, no alteration in weight taking place underthese varying conditions :0.1448 gave 0.3552 GO, and 0.0754 H20.C = 66.9 ; H = 5.8.0.1283 ,, 0.3159 CO, ,, 0'0684 H20. C=67'1; H=5.9.0-1051 ,, 5.0 C.C. N2 (moist) at 13'5O and 732 mm. N=5.4.C,,H,@,N requires C = 66.9 ; H = 5.9 ; N = 5.0 per cent.A determination of the molecular weight was made by Barger'smicroscopic method (Trans., 1904, 86, 286) in glacial acetic acid.0.060 Gram, in 1.197 grams of solvent, was intermediate between0.19 mol. and 0.20 mol., whence M.W. = 257. Cl6€Il7O,N requiresM.W. = 287.Properties of Narcissine.-The alkaloid, as before stated, isobtained by recrystallisation from alcohol in colourless prisms,which melt at 266-267O with some decomposition and formationof a red liquid. Tke crystals are insoluble in water or dilute sodiumhydroxide, but readily soluble in dilute acid.The acid solutiongives all the usual alkaloidal reactions, for example, with Meyer'sreagent, with a, solution of iodine in potassium iodide, and withphosphotungstic acid. The crystalline product is only verysparingly soluble in methyl alcohol, ethyl alcohol, ethyl acetate, oracetone, moderately so in pyridine, nitrobenzene, or glacial aceticacid, and insoluble in ether or chloroform. A determination of itssolubility in absolute ethyl alcohol showed that one part by weightof the alkaloid was soluble in 284 parts of boiling alcohol and in340 parts of alcohol at 15O.0.166 Gram, made up to 100 C.C.with absolute alcohol, gave, in a 2.2-dcm. tube at loo, a, -0*35O,whence [a] 2 - 95.8O.The alkaloid dissolves in concentrated sulphuric acid, producinga deep red solution, which slowly becomes reddish-brown on keeping.Narchissine Hydrochloride, Cl,Hl7~,N,HC1.-@3 Gram of crudenarcissine was dissolved in dilute hydrochloric acid, and the solutionevaporated to dryness over potassium hydroxide in a desiccator.The resulting crystalline product was dissolved in hot 90 per cent.alcohol, and after treatment with a, little blood-charcoal, the solu-tion, on cooling, deposited the hydrochloride in long, thin prisms,melting at 198-199O.The alkaloid is lzvorotatory.Yield, 0.27 gram :0.2737 gave 0.1176 AgCl. C1=10*6.C,6H,704N,HC1 requires c1= 10.9 per cent.THE WELLCOME PHYSIOLOGICAL RESEARCH LABORATORINS,HECNE HILL, S.E