None
When this condensation-product is reduced with sodium- amalgam, we obtain a-benzoylamidophenylpropionic* add. If the latter is now heated with concentrated hydrochloric add to 150", decomposition takes place into alcohol, benzoic add, and phenylalanine: /NH— COCH, CH,— CH,— CH -I- 2H,0 -^ \COOC,H, /NH, CA— CH,— CH + CACOOH-»-QH,OH. \COOH Phenylalanine Inactive phenylalanine may be separated into the d- and /-modifications through the cinchonine salt of the benzoyl deriva- tive." ^-Phenylalanine is the optical isomer of the natural phenylalanine. 6. Tyrosine, C9H11NO3, was obtained by Liebig" in 1846 by fusing casein with potassium hydroxide; it was isolated by Schulze and Barbieri" from sprouts of lupines and gourds and by V. Lippmann •• from the molasses of the sugar-beet. « Fischer, B. 32, 3646; 33» 2383- »' Liebig, A. 57, 127. '*Schul2se and Barbieri, B. 11, 710^ 1234; 12, 1574. "von Lippmann, B. 17, 3825. THE ASPARAGINE GROUP. 463 It crystallizes in lustrous needles melting at 235^; it dissolves with difficulty in cold water, somewhat readily in hot; it is in- soluble in ether and almost so in alcohol. In neutral and acid solutions it is tevorotatory. Tyrosine is the para-hydroxyl-derivative of phenylalanine {p 'OxyphenykUanine) : Tyro«ne Fused with potassiiun hydroxide it is decomposed into ^oxy- benzoic acid, acetic acid, and ammonia.** / Erlenmeyer and Lipp synthesized it by nitrating phenyl- alanine, reducing the nitro-derivative with tin and hydrochloric acid and fiinally treating with nitrous acid the product thus ob- tained. Erlenmeyer, jun., and Halsey ** also prepared tyrosine by employing ^oxybenzaldehyde instead of benzaldehyde in the phenylalanine synthesis from hippuric acid and benzaldehyde. c. Surinamine, CioHiaNO,, was discovered in 1824 by Hiitten- schmid** in the bark of Geoffroya surinamensis Murr. (family of the Legiuninosae), and was employed as an anthelmintic. It was later extracted from other plants and described under different names, as ratanhine*^ angdine,*^ geoffroyine,*^ and cndirine.^ Surinamine crystallizes from hot water in needles which melt with decomposition at 257®. It is little soluble in cold water and alcohol, insoluble in ether. It possesses the character of a monacid base and of a dibasic acid. Since there are only **Barth, A. 136, no. ^ Erlenmeyer, jun., and Halsey, B. 30, 3981; A. 307, 138. *' HQttenflchinid, Magadn far Pharmacie, 7, 287. * Ruge, J. 1862, 493. Kreitmair, A. 176, 64. ^Peckolt, Zeitschrift des dsterreichischen Apothekervereins, x868, 5x8. 'Winckler, Jahrhuch der Pharmacie, 2, 159. ^Hiller, A. Phann. 330, 513. 464 THE yEGETABLE ALKALOIDS. three oxygen atoms in the molecule, the alkaloid thus probably contains a phenol group. From its properties surinamine appears to be closely related to tyrosine; it is probably a higher homologue of the latter. Further data are, however, needed to determine its constitution. 6. LEUcniB. Leucine, CeHijNO,, was obtained in 1818 by Proust*^ from the putrefaction of gluten and of cheese. It is found quite widely diffused in the animal kingdom.^ It may be prepared from casein by the action of trypsin and from this and other substances by hydrolytic decomposition. It occurs also in the vegetable kingdom, as in the fimgus of the fly {Amanita muscaria Pers.), in the sprouts of vetches, lupines, gourds, in the molasses of the sugar-beet, in potatoes, in blighted com, etc. Leucine crystallizes in shining leaflets which melt at 170®. It is little soluble in cold water and alcohol, readily soluble in hot. In neutral solution it is laevo-, in acid dextrorotatory. On being heated with baryta- water to 150-160^ it is converted into inactive leucine.^ Nitric acid oxidizes it to oxycaproic acid, C5H,o(OH)COOH. Leucine is the a-amido-derivative of isocaproic or isobutylacetic acid: ch;>h-ch.-ch<^oh Leucine Schulze and Likiemik*® have, indeed, synthesized inactive leucine by successively treating isovaleraldehyde-ammonia with hydrocyanic and hydrochloric acids: ^JJjNcH— CH,— Ch/^^» -h HCN ^ Isovaleraldehyde-ammonia ^ Proust, A. ch. [2] 10, 40. *• Rdhmann, B. 30, 1978. *• Schulze, Zeitschrijt fitr physiologische Chemie, 9, 108; 10, 135. *^ Schulze and Likiernik, B. 24, 66q; 25, 56. WE ASPARAGINE CROUP. 4^5 a-Amido-iflobutylaceto-nitrile ^g»ScH— CH,— CH<(^» + 2H,0-. CH«)cH-CH,-CH<^5h + NH. Leucine It has also been synthesized by Erlenmeyer, jun., and Kunlin**" from isobutyraldehyde and hippuric acid. Under the influence of PeniciUium glaucum, inactive leucine gives rise to Jthe dextro-modification. The separation of inactive leucine into d- and /-leucine was effected by Fischer** through the cinchonine salt of the benzoyl derivative. The Meucine thus obtained is identical with the natural product. An isomeric leucine, CH,/^^~^^\COOH has been prepared by Etard and Vila *' from methylethylacetal- dehyde-ammonia. This resembles the natural leucine, but unlike the latter it possesses an intensely sweet taste and is rather soluble in water. 7« Aroininb. Arginine, CeH^N^O,, was found by Schulze and Steiger" in the young shoots of gourds and lupines, particularly in the latter. It has also been noted in beet-root " and in several coni- fers. It further occurs as a decomposition-product of animal albuminoid substances. '' Erlenmeyer, jun., and Kunlin, A. 3x6, 145. ■* Fischer, B. 33, 2370. * " Etard and Vila, C. r. 134, 122. ^Schulze and Steiger, B. 19, 1x77. Schulze, B. 24, X098. **von Lippmann, B. 29, 2645. 466 THE yEGETABLE ALKALOIDS. The salt solutions of aiginine are dextrorotatory; they are without particular physiological action. With nitrous acid arginine yields nitrogen. This indicates a primary base. When heated with baryta-water, arginine is decomposed into ammonia, urea, and omiihine, CsHuNsO,.** According to the investigations of Ellinger *' ornithine is ad- diamidavaleric acid, NHjCHj— CH,— CH,— CH(NH,)— COOH, since the action of bacteria decomposes it into carbon dioxide and tetramelhylene diamine (piUrescin): (NH,)CH,-CH,— CH,— CH(NH,)— COOH -> Ornithine CO,+ (NH,)CH,— CH,— CH,— CH,(NH,). Tetramethylene diamina This constitution is confirmed by the following synthesis of E. Fischer:" By the action of bromine on ^^-phthalimidopropylmalonic ester there is formed the corresponding brom-derivative: r-Phthalimidopropylmalonic wter C,H,<^^g^N-CH,-CH,-CH,-CBr<^^22^+HBr. r-PhthaHmidopropylbrommAlonic ester Saponification of this ester and elimination of carbon dioxide from the resulting acid give d-phihalimido-a-bramvaleric acid, CeH/^Q^N— CH,— CH,— CH,— CHBr— COOH. By treat- ing the latter with aqueous ammonia, Br is replaced by NH,. ** Schulze and Likiemik, 6. 24, 270X. Schulze and Winteistdn, B. 30, a88o; " Ellinger, B. 31, 3183; 3a, 3542. ** Fischer, Sitoungsber, KgL pr, Akad. Wiss. Berlin, 1900, xiii. THE ASPARAGINE GROUP. 4^7 Subsequent heating with hydrochloric acid gives rise to ad-diamidavaleric acid (ornithine): CeH,<^^g)>N— CH,— CH,— CH,— CH(NH,)— COOH + 2H,0 — ^COn a-PhthalimidoHK-amidovaleric acid Cai4(C00H), + (NH,)CH,— CH,— CH,— CH(NH,)— COOH. Ornithine The probable constitution of arginine is shown by its synthesis from the action of cyanamide on ornithine. The reaction takes place in aqueous solution at the ordinary temperature: CNNH, + (NH,)CH,— CH,— CH,— CH(NH,)— COOH — CyanAmide Ornithine /NH, C^NH \NH— CH,— CH,— CH,— CH(NH,)— COOH. Arginine It is, however, not quite certain whether the cyanamide adds itself to the a;-NHj group as here represented or to the a-NH, group. According to this formula arginine must be regarded as a guanidine derivative. In full conformity with this constitu- tion are the products obtained by oxidizing arginine with barium permanganate. There are thus formed guanidine, ^-guanidine- butyric add, and succinic acid.** (/-Arginine when heated with concentrated sulphuric acid is converted into the inactive modification.** 8. Ltsire. Lysine, CJclu^tO^, was first obtained by Drechsel** from the action of hot hydrochloric add and stannous chloride on ** Kutscher, Zeitschrift far physudogische Chemie, 32, 4x3. "/Wrf., 32, 476. » Drechael, B. 25, 2455. 468 THE VEGETABLE ALKALOIDS, casein. It results from the decomposition with hydrochloric acid of proteids from the seeds of conifers.** It occurs in the young sprouts of Lupinus ItUeus?^ From its yielding pentamethylene diamine {cadavenne) on decomposition with putrefaction bacilli, lysine^ appears to be ae-diamidocaproic wid:^ NH3— CH,— CH,— CH,— CH,— CH(NH,)— COOH. This constitution is confirmed by the following synthesis of Fischer and Weigert:** y-Cyanpropylmalonic ester, CN-CH,-CH,-CH,-CH<^COO^ on treatment with nitrous acid yields a-oxtmido-d'Cyanvaleric ester: CN— CH,— CH,— CH,— C(NOH)— COOQH,. Reduction with sodium and alcohol converts the latter into lysine: NH2— CHj— CH,— CH,— CH2— CH(NH,)— COOH. The artificial lysine diflFers from the natural only in being optically inactive; when warmed with hydrochloric acid to 165- 170^, however, the latter is converted into the inactive modifica- tion. 9. HISTIDINE. Histidine, CeHgNjO,, was obtained by Kossel" from the decomposition-products of a protamine. It is also formed by ** Schulze and Winterstein, Zeitschrifi far physiologische Chemie, 28, 458. " Schulze, ibid., 28, 465. •* Ellinger, B. 3a, 3542. " Fischer and Weigert, B. 35, 3772. "Kossel, Zeitschrijt jUr physiologische Chemie, 22, 181. THE ASPARAGINE GROUP. 4^9 boiling albuminous substances with hydrochloric add." It results together with lysine from the decomposition of proteids from the seeds of conifers.*' It occurs in the young sprouts of Lupinus lutetis^* and Lufnnus albus.^ Histidihe crystallizes in leaflets which are readily soluble in water, little soluble in alcohol. The free base is laevo-, its hydro- chloride dextrorotatory .•• Histidine contains an amide and a carboxyl group; litde, however, is as yet known regarding its constitution.^* It is probably a member of the asparagine group. " Hedin, Zeiischrift far physiologische Chemie, aa, 191. •• WassilicflF, Chemisches CentrMlaU, 1901, I, 786. ** Kossel and Kutscher, Zeitschrift far physiologische Chemie^ 38, 382. ^^Herzog, Zeitschrift far physiologische Chemie^ 37, 248. Weigert, ibid^ 39> 213- Frftnkel, M. 24, 239/ CHAPTER XXXVI. THE CHOLINE GROUP. This group includes three alkaloids, all of which are closely related in constitution. 1. Choline CjHwNOy 2. Muscarine C^HjjNO,. 3. Betaine C^JSiOy I. Cholinb. Choline (sincaUne^ bilineurine^ amaniiine) was obtained by Babo and Hirschbrunn^ in 1851 by the decomposition of sinapine with barium hydroxide and was described by them under the name of sincaline. In 1875 Schmiedeberg and Hamack ' found choline in toad- stool {Amanita muscaria Pers.) and gave it the name amaniiine; it occurs in this fungus together with muscarine. Its name, choline, was given by Strecker,* who isolated the base from animal gall (jt^A^). Of all the alkaloids choline is found most widely distributed throughout the vegetable kingdom; it is formed indiflFerently in the most varied plant species which bear no botanical relation to one another. It is probable that it is a product constantly occurring in the vital processes of the plant and necessary in the building up of the plant-cells. Choline has been observed in the seeds of the pea, oat, sesame, hemp, lupine, barley, gourd, vetch, lentil, bean, cotton-plant, and goat's horn; in the fruit of the common beech, in the betel- ^ Babo and Hiischbrunn, A. S4, 10. 'Schmiedeberg and Hamack, Chemisches CetUralblaU^ 1875, 629. •Strecker, A. 123, 353; 148, 76. 470 THE CHOLINE CROUP. 47 1 nut, in bitter almonds, in potatoes, beets, in morels and other fungi, in the roots of the ipecacuanha, of the calamus, in the leaves of the belladonna, henbane, clover, in tea, etc.; it has also been noted in wine and beer. Choline is also found, as has been indicated, in the animal organism. Liebreich obtained it in 1865 by treating the brain of an ox with barium hydroxide. It is ordinarily prepared by boiling the yolk of the egg with baryta-water. These different animal and plant products contain choline not originally as such, but in the form of complicated derivatives which are known as lecithins — ^basic bodies soluble in water, alcohol, and ether. By the action of acids or of alkalies the lecithins are decom- posed into choline, glycerine, phosphoric acid, and higher fatty acids. Because of this decomposition they are represented by the following general formula: /O— R CjHj — O— R' ypwTT in which R and R^ designate the radicals of stearic, palmitic^, or oleic acid. The lecithins play an important role in the plant organism. They appear to be closely related to the chlorophyll; it is possible, indeed, that chlorophyll itself is to be classed among these sub- stances and that their formation is due to its decomposition. This view, however, is at present largely speculative. Choline forms a non-crystallizable sirup which deliquesces in the air and dissolves in water in all proportions. It is strongly alkaline in reaction; physiologically its action is slight. It is a quaternary base of the ammonium type; its nitrogen atom is pentatomic with one of its valences attached to a hydroxyl group. Its salts are formed with the elimination of water, the hydroxyl being replaced by an acid radical: 47* THE yEGETABLE ALKALOIDS. C,H,pN— OH+HCl — C^, =N— CI +H,0. Chofioe ChoKiM hydrochloride Choline is trimethyl oxyethyl ammonium hydroxide: ^CH,— CH,— OH Choline (CH.)^<^OH Its constitution is established by the following syntheses: i'. Choline hydrochloride is formed when trimethylamine is heated with glycol chlorhydrin:* (CH3)^N+CH,C1— CH,OH-- (CH,)^N/^f^ =n/ch3-ch,-oh Trimethylamine Glycol chlorhydrin Choline hydrochloride 2'. ChoUne itself results from the action of ethylene oxide on an aqueous solution of trimethylamine at the ordinary tem- perature:* (CH,)^N+CH,-CH,+H,0-* (CH,)^N/^g»~^^*~^^ Trimethylamine \ / ^oUne Ethylene oxide 3'. If ethylene bromide acts upon trimethylamine and the resulting addition-product, bromethyl trtmeihyl ammonium bromide^ IS treated with silver nitrate, choline nitrate is formed:* (CH,),=N-hCH,Br-<:H,Br- (CH,)^N<^^J^»~^^^^ (CH.)^N<^^J^»~^^®'" -h2AgNO,+H,0-* (CH,)^N<(g^^-^^'-^^ +2AgBr+HNO.. «Wtirtz, C. r. 65, 1015. *Bode, A. 367, 371; A. Pharm. 229, 469. THE CHOLINE CROUP. 473 The constitution of choline also follows from its decompo- sition-products; when a concentrated aqueous solution of cho- line is boiled, the base is decomposed into trimethylamine and glycol. Choline is of particular interest because of its relation to the opium alkaloids. Thus morphine when decomposed yields a biase, dimethyl-oxyethylamine, (CH,)^ — CHj — CH, — OH, which with methyl iodide gives the hydriodide of choline. From this morphine as well as codeine and thebalne appear to be choline derivatives (page 277). Choline hydrochloride with acetyl and benzoyl chlorides forms acetyl and benzoyl derivatives (proof of the hydroxyl group).* When this same hydrochloride is heated with hydriodic acid to 120-150^ the iodide (CH,)^=NI— CH,— Ciy, is obtained. Moist silver oxide transforms this derivative intQ trimethyl vinyl ammonium hydroxide: (CH.)=N<(gH=CH. This last substance is identical with neurinCy an extremely poisonous base, which was discovered in 1865 by Liebreich at the same time as choline on treating ox-brain with baryta- water.' By the action of oxidizing agents (nitric add, chromic acid, potassiiun permanganate) choline is changed to betaine. 2. HUSCARIITB. This base is the poisonous principle of the mushroom {Amanita muscaria Pers.). It was isolated from this by Schmiedeberg and Koppe * in 1870. It is also found in some other poisonous • Bayer, A. 142, 325. ^Ibid., 140, 311. 'Schmiedeberg and Koppe, B. 3, 281. 474 THE ySGETjIBLE ALKALOIDS. fungi, to which possibly it imparts the poisonous character; also, according to Marino-Zucco and Vignolo,* in the flowers and fruit of Cannabis indica, family of the Cannabinaceae. It forms deliquescent crystals which are quite soluble in water and alcohol, insoluble in ether. It is a strong base without odor or taste and is highly poisonous. When heated it is de- composed, trimethylamine being formed. Muscarine like choline then is to be regarded as an ammonium hydroxide; in the formation of its salts a hydroxyl group is re- placed by an acid radical: QH„O^N--OH -hHCl — C5H,,0^N— CI -hH,0. Muscarine Muscarine hydrochloride The constitution of muscarine has not as yet been fully de- termined. Until recent years it was regarded as acetal tri- methyl anmionium hydroxide: Attempts to S3mthesize muscarine, however, have cast some doubt on the above constitution. Fischer," by methylating acetal-amine and Berlinerblau " from trimethylamine and chlor- acetal, obtained bases mutually identical but diflFerent from the natural muscarine. Fischer further showed that the snythe- sized base possessed the constitution represented, since oxidation with silver oxide converted it into betaine: (CH.)^N<^g§-^°°H +H,0. Betaine * Marino-Zucco and Vignolo, G. 25, 262. " E. Fischer, B. 26, 468; 27, 165. " Berlinerblau, B. 17, T139. THE CHOUNE GROUP. 475 On the other hand, in favor of the above constitution for muscarine is the statement of Schmiedeberg and Hamack " that muscarine is formed by the oxidation of choline with nitric acid: Choline (CH.)^N<^g^»-^^(^^)» Mufcarine (?) The product thus obtained, indeed, closely resembles the natural muscarine, but, as careful study has shown, it is not iden- tical with the latter.*' An isomuscarine, (CH.)-n/CH(OH)-CH.OH ^\0H has been prepared by Bode." 3. Betaihe. Betaine was discovered by Scheibler ** in 1869 in beet-root {Beta vulgaris L., family of the Chenopodiaceae), where it is found associated with a large nimiber of other organic substances, such as malic, tartaric, oxalic, citric, aconitic, tricarballylic, aspartic acids, and such bases as choline, xanthine, hypoxanthine, guanine, asparagine, etc. In unripe beets its quantity amounts to about 0.25%, in the ripe it decreases to 0.1%; in the molasses the base is found in much larger quantity, often as high as 3%. Betaine occurs also in other plants, accompanied ordinarily by choline and trigonelline. It has been. obtained from cotton- ^ Schmiedeberg and Harnack, Archiv far experimetUelle Pathologic, 6, loi; J. 1876, 804. » Nothnagel, B: 26," 801. *<Bode, A. 267, 291. '•Scheibler, B. a, 292; 3, 155; Zeitschrijt fiir Chemie, 9, 279. 47^ THE ySGETABLE ALKALOIDS. seed, from the barley, the vetch, from Chenopodium album L., Artemisia Cina Beig., Lycium barbarum L., Scopolia atropaides Bercht., from the leaves of the potato, and from the root of AUluta officinalis. Emmerling *• noted its occurrence among the products result- ing from the putrefaction of gluten. It crystallizes from alcohol in large, hygroscopic crystals which are sweet and refreshing to the taste. It is readily soluble in water and alcohol, insoluble in ether. Betaine is a weak base, neutral in reaction, optically inactive, and non-poisonous. Like choline and muscarine it is a quaternary ammonium base: CsH^O^N— OH CsH^O^N— CI Betaine Betaine hydrochloride The constitution of betaine is shown by its different S)mtheses. It is the methyl hydroxide of dimeihylglycocoU: (CH.)^<g5-C00H Betaine easily loses the elements of a molecule of water; to effect this it suffices to heat the substance to loo^ or simply to let it stand over sulphuric acid. The resulting anhydride (melting-point 150®), (CH,)^N— CH, O— CO is the prototype of the so-called organic beiaines. Betaine may be prepared: i'. By the oxidation of choline with chromic acid or potas- sium permanganate: ^^ ''Emmerling, B. 29, 3731. " liebreich, B. 2, 12, 167; 3, 761. THE CHOUNE GROUP. 477 C^^Hno Betalne 2'. By the condensation of trimethylamine with monochlor- acetic acid:*' (CH3)bN+CH,C1— COOH-* (CHa),N/^f'»" :,— cooH Trimethylamine Chloracetic add Betalne hydrochloride 3'. By the action of methyl iodide on glycocoll in the presence of an alkali:" NH,— CH,— COOH+3CH^+3KOH-*. Glycocoll (CH.),N<^; CH,-COOH^^^^^jj^Q BeUlne Sarcodne, C^HyNO,. — Sarcosine, which was discovered by Liebig" in 1847 i^ the decomposition-products of creatine, is closely related to betaine. It has been obtained by Rosengarten and Strecker ^ by boiling caflFeine with baryta- water. It crystal- lizes in rhombic prisms which dissolve readily in water but with difficulty in alcohol; it tastes sweet and melts with decom- position at 210-215°. Sarcosine is methylglycocoll (methylamidoacetic acid): CHaNH— CH,— COOH. Sarconne Its constitution is indicated by its synthesis from methylamine and chloracetic acid.** " Griess, B. 8, 1406. *• Liebig, A. 6a, 310. ^ Rosengarten and Strecker, A. 157, x. » Volhard, A. 123. 261. 478 THE yEGETABLB ALK/tLOIDS. The relation between saicosine and betaine is shown in the following fonnulae: CH,— NHCH, CH,— N(CH,)./Qg» COOH Suoosine (UMhylglycaooU) COOH Betaine (DimethrlglycoooU mathyl hydrosidB) CHAPTER XXXVn. ALKALOIDS OF THE MUSTARD-SEED. The seeds of the mustard, Sinapis alba L. and Sinapis nigra L. (family of the Crucifers)} contain two alkaloids: Sinapine. . . ^ CieHjsNOe Sinalbin Ct^4:i^^20i^ The former is found in black mustard, the latter in white. In black mustard there occurs furthermore a glucoside, the potassimn salt of myronic acid, CioHieNSjKOg+HaO. When saponified this yields glucose, allyl mustard-oil, and potassiimi bisulphate. I. SniAPINE. Sinapine was discovered by Henry and Garot * in 1825. It is obtained in the form of its difficultly soluble sulphocyanate Ci^34NO5-SCN+Ha0 by adding potassimn sulphocyanate to an alcoholic extract of mustard-seed. Sinapine also results from the decomposition of sinalbin.' According to Gadamer' sinapine occurs in black mustard but not in white; the latter contains only sinalbin, which in its decomposition 3delds sinapine. Sinapine is not known in the free state. If we attempt to isolate it from any of its salts, we obtain a deep yellow solution of strongly alkaline reaction. When, however, the solvent is driven off, the alkaloid suffers decomposition. This decomposition takes place still more readily if the aqueous ^ Heniy and Gaiot, Journal de pkarmacie, [2] ao, 63; 4a, x. 'Will and Laubenheimer, A. 199, 150. 'Gadamer, A. Pharm. 235, 44, 81; B. 30, 2322, 2330. 479 4^0 THE VEGET/IBLE ALKALOIDS. solution is heated with an alkali; there are thus formed choline and sinapic acid: ^ C,eH«NOe+H,0-* C^i^Oj + CnH^Og. Sinapine Choline Siiutpic acid The constitution of choline we have already learned (page 472); that of sinapic acid was studied by Remsen and Coale^ and later by Gadamer. Sinapic add crystallizes from alcohol in prisms which melt at 191-192**; at a higher temperature the add is decomposed. It is little soluble in cold alcohol and still less in water and ether. It is a monobasic acid; treated with alcohol and hydrochloric add it yields an ester. It contains two methoxyls (method of Zeisel) and one hydroxyl (acetyl derivative). When treated with methyl iodide in alkaline solution it yields the methyl ester of melhylsinapic acid (melting- point 91®): CaH,(OCH,),(OH)(COOH) + 2NaOH + 2CH,I — Sinapic acid C,H4(OCH,),COOCH, + 2NaI + 2H,0. Methylsinapic methyl ester By the saponification of this ester with alcoholic potash the free methylsinapic acid, CaH4(OCH,),COOH, is obtained (needles melting at 124®). On oxidizing methylsinapic acid with potassium perman- ganate in alkaline solution, Gadamer obtained trimethylgailic acid: CH,o— / ^,— COOH CH,C 6CH, * Babo and Hirschbrunn, A. 84, 10. * Remsen and Coale, Am. Chem. Jour. 6, 50. ALKALOIDS OF THE MUSTARD^EED. 481 From this may be deduced either of the two following formulas for sinapic acid: CHjO— /^— CH=CH— COOH CH,0— j^^Nj— CH=CH— COOH HO— I J ^^ CH,C OCH^ I II To determine which of these represents the acid, Gadamer prepared its acetyl derivative and oxidized this with potassium permanganate. On saponifying the oxidation-product he obtained a dimethyl- gallic add which proved to be identical with syringaic acid (melting-point 202^), whose constitution had already been shown by Koemer* to be — COOH >CH, Consequently the constitution of sinapic acid is expressed by formula I. This constitution has been recently confirmed by the synthesis of sinapic acid from the dimethyl ether of pyrogallol.' By the action of chloroform and caustic soda on the latter (reaction of Reimer-Tiemann) it is converted into syringaic aldehyde. If this aldehyde is now condensed with sodium acetate and acetic anhy- dride, sinapic acid is formed. The course of the reaction may be formulated as follows: CHjO— /^--CH=CH— COOH OCH, OCH, Dimethyl ether Syringaic aldehyde Sinapic acid of pyrogallol *Koemer, G. 18, 209. ' Gruebc and Martz, B. 36, 215, 103 1. 48a THE VEGETABLE ALKALOIDS, Now, sinapine is the product representing the union of sinapic acid and choline with the elimination of one molecule of water; it is, furthermore, a quaternary base. Its constitution must, therefore, be expressed by the following formula: s Sinapine 2. SINALBIN. Sinalbin was discovered in white mustard by Will and Lauben- heimer in 1879. It crystallizes from dilute alcohol in prismatic needles which contain five molecules of water of crystallization and which melt at 83-S4®; in the anhydrous condition it melts at 139-140®. It is little soluble in water and cold alcohol, insoluble in ether. Its aqueous solutions react alkaline, taste very bitter, and are laevorotatory. Alkalies color them a deep yellow. Sinalbin is a glucoside; it is readily decomposed by diflFerent agents, particularly by myrosin, a ferment whicn is found in the mustard-seed. Sinalbin is thus decomposed into dextrose, sinapine sulphate, and a substance, CgHjNSO, which proves to be sinalbin mustard^oU: C,oH«N,S,0«-hH,0^ Sinalbin C,HuO.+C„H„NO,HSO,+C,H,NSO. Dextroae Sinapine bisulphate Sinalbin mustard-oil This decomposition of sinalbin under the action of myiosin is effected by simply allowing powdered mustard-seeds to stand in contact with water. The derivative, C8H7NSO, is a yellow oil possessing a very sharp taste and acting upon the skin as a strong irritant It is almost insoluble in water, but dissolves readily in alcohol, ether, and in alkalies. ALKALOIDS OF THE MUSTARD-SEED. 4^$ Its constitution was pointed out by Salkowski.* This in- vestigator found that the derivative was identical with p-oxy- benzyl isosulphocyanate, C^/^ OHM ' which he obtained by treating ^-oxybenzylamine with carbon bisulphide.- With mercuric chloride or sulphate or silver nitrate, sinalbin forms white precipitates. When these are treated with hydrogen sulphide a decomposition ensues which resembles that resulting from the action of myrosin on sinalbin: CaoH43N,S,0|,+H,0 — Sinalbin C,H„0,+CmH,«NO,HSO,+C,H,NO+S. Dextroae Sinapioe bisulphate The body, C»H,NO (mdting-point 69°), yields on saponifica- tion ammonia and p-oxyphenylacelic acid, CJEI,0,. It is accord- ingly the nitrile of the latter acid: rw/' CH,— CN(i) 0H(4) From these considerations the following constitution has been assigned to sinalbin: yO— Sa— O— N(CH,)r-CH,--CH,— 0-<:0— CH=:CH--C,H,(OCH,),OH Ct-S — CiHiiOf ^N— CH,— C,H4— OH W (4) 'Salkowski, B. as, ^137. CHAPTER XXXVm. TRIMETHYLAMINE. Lice the bases of the choline group trimethylamine does not appear to be a product of assimilation in the vital processes of the plant, but results rather from the decomposition of more complex substances, such as the lecithins and choline. Trimethylamine has been observed in a large number of plants. It was discovered in the leaves of Chenopodium vulvaria L. (family of the Chenopodiaceae) by Dessaignes Mn 1851. Later it was found in the blossoms of the hawthorn, mountain-ash^ wild-brier, and pear-tree, in the seed of the beech- tree, in Arnica. matUana L., in Mercurialis annua, in ergot, in the toadstool^ in beet-root, etc. It is obtained from these plants by simply distilling them with water and alkali. One might possibly infer that the trimethyl- amine is formed during this process from the immediate decom- position of more complex basic derivatives. This, however^ is not the case; from investigations of Wicke ' trimethylamine is shown to be present as such in the plant. The same year in which trimethylamine was discovered it was synthesized by Hofmann • by the action of methyl iodide on ammonia. Trimethylamine is a strong base (boiling-point 3.5^). It dissolves in water, alcohol, and ether in all proportions, and possesses a disagreeable fish-like odor. * Dessaignes, C. r. 33, 358; 43, 670. 'Wicke, A. 91, 121; 124, 338. 'Hofmann, A. 79, 11; 83, 116. 484 TRIMETHYLAMINE. A^S Alkylamines other than trimethylamine are seldom met with in plants. Dimethylamine has been noted in decayed mushrooms, methylamine in the molasses of the sugar-beet and in Mercurialis cnnuOf ^ eihylamine has been found in spoiled wheaten flour, and propylamine has been detected in ergot.^ * Schmidt, A. 193, 73. *Wenzell, J. 1864, 14. CHAPTER XXXIX. ALKALOIDS OF UNKNOWN CONSTITUTION. Of the remaining alkaloids whose empirical formula may be regarded as fairly well established, but whose constitution is ' as yet unknown, we shall mention the following: 1. Stachydrine, C^i^Oj+HjO.— In the tubercles of Stackys tuberifera Bunge (Labiatae); in the leaves of CUrus AuratUium L. Deliquescent crystals, quite soluble in water. Melting-point 210°. Contains a carboxyl and two ft-methyls. Is decomposed by very concentrated alkali, dimethylamine being evolved. 2. Alkaloids from the Leaves of Ephedra vulgaris Rich. (Conif eras) : Ephedrin€f Ci^HigNO. Crystals; boils without decomposition at 255®. A secondary base. When heated with gold chloride in aqueous solution it yields methylamine and benzaldehyde. From Ephedra monostachia an alkaloid, C^HioNO, has been isolated^ which also bears the name ephedrine; this forms crystals melt- ing at 112®. Pseudoephedrine^ CioHigNO. Crystals, melting at 114-115°. A secondar}' base, bitter in taste.. Contains a hydroxyl. On oxidation with potassium permanganate yields benzoic acid. The action of concentrated hydrochloric acid at 180® gives rise to methylamine and an oil, which on oxidation is converted into benzoic acid. 3. Damasceniney C9H11NO3. — ^In the seeds of Nigella Datnas- cena L. (Ranunculaceae). Prisms. Melting-point 27°. Boil- ing-point 168°. Contains two methoxyl groups. Its salts fluoresce. 4. Jambosiney CioHiftNOj. — In the bark of Myrtus Jambosa (Myrtaceae). Crystals, melting at 77°; soluble in alkalies. 4S6 ALKALOIDS OF UNKNOIVN CONSTITUTION. A^7 5* Alkaloids from Cacti. — ^In different species of the genus Anhalanium (family of the Cactaceae) are found the following alkaloids, which in the plant are in combination with malic acid: a. Anhaline, CiJ^^NOj. Prisms. Melting-point 115°. b. Mezcaline, ChH^NO,. Needles, melting at 151^; soluble in water. Contains three methoxyls and a n-methyl. A strong tertiary base. c. Anhalonidine, CiaHuNOg. Needles, melting at 160°; readily soluble in water. Contains two methoxyls, but neither hydroxyl nor »-methyl. Inactive. Its salts are dextrorotatory. d. Ankalonine, CuHi^NO,- Secondary base. Needles. Melt- ing-point 85^. Boils without decomposition. Contains a methoxyl but no hydroxyl. Its salts are laevorotatory. e. Lophophorine, CuHjjNOj. An oil. Inactive. Contains a methoxyl but no n-methyl. Very poisonous. /. PeUoiine, CjJHuNO,. Plates, melting at no®; insoluble in water, soluble in organic solvents. A tertiary base. Acts as a narcotic. Contains a hydroxyl, a n-methyl, and two methoxyls. On distillation over zinc-dust or soda-lime yields trimethylamine. 6. Carpaine, C^Hj^O,. — In the leaves of Carica Papaya L. (Passifloraceae). Rhombic prisms, melting at 121®. May be sublimed. Insoluble in alkalies. A secondary base, dextro- rotatory. Contains a hydroxyl. 7. Chrysanthemine, CuHjgNjOj. — In the blossoms of Chrys- anthemum cinerariafolium Vis. (Compositae). Deliquescent needles. Diacid base. Inactive. Contains one hydroxyl and one NH group. On distillation over soda-lime, trimethylamine and a pyridine base are formed. Oxidation gives rise to tri- methylamine and succinic acid. Heated with caustic potash chrysanthemine is decomposed into trimethylamine, ^--oxybutyric acid and an acid, C5H10N — COOH (piperidine carboxylic acid) ; heated with concentrated hydriodic acid it yields alkyl iodides and a methylpiperidine carboxylic acid. Under the action of superheated steam piperidine derivatives are also formed. 8. Caffearine, CHHteNa04. — In coffee (Coffea arahica L., family of the Rubiaceae). Deliquescent needles, very soluble in 483 THE yEGETABLE ALKALOIDS. water. ' Melting-point 140^ Monacid base, inactive. In physio- logical action, a narcotic. 9. Eserine (physosHgmine)^ CnHjiNjO,. — ^In Calabar beans, the seed of Physostigma venenosum Balf. (Leguminosse). Prisms. Melting-point 105-106^. Tertiary, monacid base, in reaction alkaline. Laevorotatory. Extremely poisonous. Causes contrac- tion of the pupil. Contains a hydroxyl and two n-methyls. When boiled with potassium hydroxide or distilled over zinc- dust yields methylamine. 10. Matrine, Cj5Hj4N,0. — ^In the root of Sophora angusti- folia Sieb. (Leguminosae). Melting-point 80^. Dextrorotatory. Readily soluble in water. 11. Piliganinei Ci5H24NaO. — In Lycopodium Saururus Lam. (Lycopodiaceae). Needles, melting at 64-65®; readily soluble in water. Very poisonous. Acts as a purgative and an emetic. 12. Piperovatine, CiJHaiNO,. — In Piper avatum Vahl. (Piper- aceae). Needles, melting at 123®. A very weak base, inactive, neutral in reaction. When heated with water to 160° yields a pyridine base. 13. Paricine, CieHjgNjO. — In the bark of Cinchona sue- cirubra Pav. (Rubiaceae), which contains furthermore the prin- cipal cinchona alkaloids. A yellow, amorphous powder. Melt- ing-point 130®. A monacid base, inactive. 14. Ricinine, C17H18N4O4. — In the seed of Ricinus communis L. (Euphorbiaceae). Plates, melting at 194^ Neutral reaction. Inactive. Is decomposed by alkali into methyl alcohol and an acid, C15H14N4O4. 15. Bebeerine (pdosine), CigH^iNO,. — ^In the bark of Nee- iandra Rodim Schomb., of Hemandia sonora L. (Lauraceas), and of Cissampelos Pareira L. (Menispermaceae). Amorphous powder, soluble in alkalies, laevorotatory. Melting-point 180°. A tertiary base. Contains a methoxyl, a n-methyl, and a hydroxyl, but no carboxyl. On distillation with caustic potash yields methylamine and pyrrol; with zinc-dust, o-cresol and methyl- amine. Nitric acid gives rise to nitro-derivatives. Possesses febrifugal properties. ALAKLOIDS OF UNKNOIVN CONSTITUTION, 4^9 Buxine, CieH^iNOg, which is obtained from the bark of Buxus sempervirens L. (Euphorbiaceae), and which was supposed to be identical with bebeerine, appears to be a distinct alkaloid. i6. Senecionine, CisHjeNOe- — In groundsel {Senecio vulgaris L., Compositae). Crystalline, laevorotatory. 17. Nuphariney CigH34N302. — In the rhizome of the water- lily (Nuphar luteum Sibth., Nymphaeaceae). Amorphous, in- active. i8. Alkaloids from the Bark of Geissospermum VeUosii Allem. (Apocynaceae). — ^This bark has been employed as a feb- rifuge. a. Pereirine, CjeH^NjO. Amorphous, monacid base. Melt- ing-point 124°. b. Geissospermine, Ci»H34Na02+HaO. Prisms, melting at 160°. Monacid base, laevorotatory. c. VellosinCy C28H28N2O4. Plates, melting at 189°. Monacid, tertiary base, dextrorotatory, very poisonous. Contains two methoxyls. 19. Alkaloids from Angustura Bark {Gdipea Cusparia Rut., Rutaceae). — ^This bark is also employed as a febrifuge. It con- tains in the free condition the following four tertiary bases, which are all crystalline: a. Cusparine, CjoHigNOj. Melting-point 92°. Is decom- posed by caustic potash into an aromatic acid and a basic body. b. Cusparidine, C19H17NO3. Melting-point 79°. c, Gdipiney CjoHjiNOs- Melting-point 115®. d, Galipidine, CieHjaNOj. Melting-point 110°. 20. Achilleinei CjoHjgNjOio. In Achillea Millefolium L. and A. moschata Jacq. (Compositae). Amorphous mass of red- dish-brown color, deliquescent, soluble in water with a yellow color. When boiled with dilute sulphuric acid, is decomposed into a sugar, ammonia, a volatile aromatic substance, and an amorphous base, achilletine, CnH^NO^. 21. Alkaloids of the Celandine. — ^The following Papaveraceae — celandine (Chdidonium majus L.), Sanguinaria canadensis L., Stylophorum diaphyllum Nutt., Bocconia jnUescens Wild., and 49^ THE yEGETABLE ALKALOIDS. Macleya cordala R. Br. — contain in addition to protopine (page 294) the following six alkaloids, which in the plant tfre in com- bination with the acids — ^malic, succinic, citric, and chelidonic (page 21). a. ChelidoninCj CjoHieNOj+HjO. Plates or needles, melt- ing at 135-136°. Tertiary base. Colorless salts. Oxidation with potassium permanganate gives rise to oxalic acid and methylamine. Contains a hydroxyl, a f^methyl, but no methoxyl group. Is dextrorotatory. b. Cheleryihrine, C21H17NO4. Crystals, melting at 203°. Its salts are yellow and exhibit a violet fluorescence. Burning to the taste; inhaled in powdered form provokes sneezing. In- active. Contains two methoxyls. c. Sanguinarine, C2oHi5N04+HaO. Needles, melting at 213°. Red salts with violet fluorescence. Sharp taste. Provokes sneezing. Inactive. Contains one methoxyl. d. a-Hafnochelidonine, C21H21NO5. Melting-point 182°. e. P'Homochelidonine, CjiHjsNOg. Melting-point 159°. /. y-Homochelidonine, CjiH^jNOj. Melting-point 169°. The last three alkaloids are crystalline and contain two methoxyls. Some of the alkaloids mentioned above are found in other plants than in those named, as in Adlumia Cirrhosa Raf. (Fuma- riaceae) and in Eschscholtzia calijornica. 22. Fumarine, C,iHi^04. — InFufnaria officinalis L. (Fuma- riaceae). Prisms, melting at 199°. Optically active. 23. Rhoeadiney CjiHjiNOa. — In the poppy (Papaver Khcsas L., Papaveraceae). Prisms. Melting-point 232®. Weak base- Sublimes in an atmosphere of carbon dioxide. 24. ArtarinCy C21H28NO4. — In the bark of Xanthoxylum Senegalense DC. (Rutaceae). Amorphous powder of grayish- red color; melts with decomposition at 240°. Yellow salts. 25 Abrotiney CjiHjsNjO. — ^In Artemisia Abroianum L. (Com- positae). Needles, readily soluble in hot water; the solution shows a blue fluorescence. Diacid base. 26. Alkaloids of the Quebracho Barks. — ^The bark of Aspi- ALKALOIDS OF UNKNOIVN CONSTITUTION. 49 ^ dosperma Quebracho Schlecht. (Apocynaceae) is used as a febri- fuge. It contains the following six alkaloids in combination with tannic acid: a. Quebrachine, CjiHj^NjOj. Needles, melting at 214-216®, dextrorotatory, insoluble in water. b. Hypoquebrachine, CjiH^NjOj. A yellow, amorphous mass, melting near 80®. c. Quebrachamine. Leaflets. Melting-point 142°. d. Aspidospermine J C^^^^O^. Prisms. Melting-point 205- 206°. Very weak base, laevorotatory; neutral in reaction; soluble in water with difficulty. Boiled with caustic potash, is decom- posed into pyridine, quinoline, and similar smelling bases. e. Aspidospermatinef CjiHjgNjO,. Needles, somewhat solu- ble in water. Melting-point 162°. Laevorotatory. /. Aspidosamine, CjjHjsNjOa. Flocculent precipitate. Melt- ing-point near 100°. The bark of one tree of the genus Aspidosperma contains paytine, CjiHj^NjO-f HjO (prisms, melting-point 156°, laevo- rotatory), and paytamine, C21H24N2O (amorphous). The bark of Quebracho Colorado {Loxopterygium Lorenizii, Griesebach, Anacardiaceae) contaihs as active principal, Loxop- ierygine, C2eH84N202. Amorphous; melts at 81°; is decom- posed at higher temperatures, giving apparently quinoline. All these alkaloids are monacid bases. 27. Alkaloids of the Alstonia Barks (Apocynaceae). — ^These barks are valued for their febrifugal properties. Alstonia con- stricta Muell. contains: a. Alstonine (Chlorogenine), CjiHjoNjO^-hsiHjO. A brown, amorphous mass, soluble in water. Melts in the anhydrous condition at about 195°. J. Porphyrine, CziHjjNbOj. Melting-point 97°. The solutions of both these alkaloids show a blue fluorescence. Alstonia spectabilis R. Br. and A, scholaris R. Br. contain: c. Ditamine, CieHijNO,. Amorphous powder. Melting-point 75°. d. EckUamitte (dltaine), C2jH.,N,04+4H,0. Prisms, melting 492 . THE yEGETABLE yiLKALOlDS. with decomposition at 206°; readily soluble in water. Laevo- rotatory. Strongly basic; possibly a quaternary base. e. Echitenine, CjoHjyNO^. A brown, amorphous substance. All these alkaloids are monacid bases. 28. Hymenodictine, CjsH^oNj. — ^In the bark of Hymenodiciyon excdsum Wall. (Rubiaceae). Needles, melting at 66°. Diacid and bitertiary base. 29. Aribine, CjsHjoN^-f 8H3O. — ^In the bark of Arariba rubra Mart. (Rubiaceae). Prisms. Melting-point of the anhy- drous base 229°. Sublimes without decomposition. A strong base, inactive, diacid, and bitertiary. 30. Yohimbine^ CjsHjoNjO^. — In the bark and leaves of the Yohinibi- or YunibehooriTtt (Rubiaceae). White needles. Melt- ing-point 234°. Dextrorotatory. Monacid, tertiary base. Con- tains a hydroxyl (acetyl derivative) and a methoxyl. Is the methyl ester of a carboxylic acid. Oxidation with potassium chlorate gives rise to formic acid; with potassium permanganate, to yohimbic acid, CaoH24N20e, and noryohymbic acid, C^^ift^iOi- Phenylhydrazine is without action. The salts of yohimbine are formed with the elimination of a molecule of water. With yohimbine is found a second alkaloid, yohimbenine, 31. Conessine (WrigfUine), C24H40N2. — Contained as tannate in the bark and seeds of Wrightia antidysenterica R. Br. of Holarrhena ajricana DC, and of H. aviidysenterica Wall. (Apocynaceae). Needles, melting at 122®; may be sublimed. Diacid and bitertiary base. 32. Alkaloids from the Seeds of the Stavesacre {Delphinium Staphisagria L., Ranunculaceae) : Delphinine, CjjHjjNO^. Plates. Melting-point 120°. Inac- tive. Very poisonous; in physiological action resembles vera- trine and aconitine. A weak base. Ddphinaidine, CjgH^jNO^. Amorphous. Melting-point iio- 120°. Inactive. Ddphtsine, Cj^H^cNaO^. Crystals, melting at 189^ ALKALOIDS OF UNKNOfVN CONSTITUTION. 493 Siaphisagrin€y CmH„NOj. Amorphous. Melting-point near 90®. Inactive. 33. Alkaloids from the Root of the Yellow Jasmine (Gdse- mium sempervirens Pars., Apocynaceae). Gdsemine, C24H2,N304. Crystals, melting at 45^; soluble in alkalies. Strong, monacid base, very poisonous. Gelseminine, CajHj^NjOg. Crystallizes. Melting-point 172°. Monacid, tertiary base, soluble in alkalies. Contains no methoxyl group. 34. Paucine, Ca7H8,N505 4-6iHaO. — ^In Pauco-nuts, the fruit of Pentaclethra macrophyUa Benth. (Leguminosae). Yellow leaflets, melting at 126^; soluble in water and alkalies. Diacid base. Is decomposed by concentrated hydrochloric acid or caustic soda into dimethylamine and pyridine bases. 35. Erythrophleine, CjgH^^NO^ or CjaH^jNOj.— In the root of ErythrophUBum guinense Dow. (Leguminosae). Crystalline, very poisonous, producing eflFects similar to those resulting from the action of digitalin. Is decomposed by concentrated hydro- chloric acid into methylamine and an acid, erythrophleic acid, 36. Alkaloids from the Seeds of Vicia saliva L. and Vicia Faba minor (Leguminosae). Vicine, CagHjiNiiOai or (CgHijNjOe). Is found in beet-root. Needles, soluble in dilute alkali. Boiling with dilute sulphuric acid eflFects decomposition into ammonia, a sugar, and the so- called divicine. Fusion with caustic potash gives rise to ammonia and potassium cyanide. Convicine, CioHijNjOy-hHjO. Leaflets. By the action of mineral acids alloxantin is formed. 37. JEmetine, C,oH,oN,05 or C3oH«Nj04.— In the root of the ipecacuanha (Cephaelis Ipecacuanha Wild., Rubiaceae). Amor- phous powder. Melting-point 70°. Acts as an emetic. Diacid, bitertiary base, optically inactive. Contains a hydroxyl and four methpxyls. Is decomposed by caustic potash into ammonia and quinoline bases. With emetine apparently occur two other alkaloids, cephaeline, C^^oNjO^, and psychotrine. 494 THE yEGETABLE ALKALOIDS. 38. Lycopodine, C^HoNjO,. — In Lycopodiutn complanatum L. (Lycopodiaceae). Prisms, melting at 114-115^ Diacid base. 39. Imperialine, CajHeoNO^. — In the bulbs of FrUUlaria imperialis L. (Liliaceae). Needles, melting at 254^. Laevoro- tatory. 40. Ergotinine (e^boliTte), CMH^oN^Oe-^In ergot. Prisms, soluble in excess of alkali. In aqueous solution gives a violet fluorescence. A weak, monacid base, dextrorotatory. Acts as a hemostatic. 41. Taxine, C87H53NO10. — ^In the seed and leaves of the yew {Taxus baccata L., Coniferae). Amorphous powder. Melt- ing-point 82°. Tertiar}' base. Narcotic. 42. Solaninei CijHtsNOh or C43H75NO1J. — In the berries of the common nightshade (Solanum nigrum L., Solanaceae); in the woody nightshade (5. Dulcamara L.); in the young shoots of the potato (5. tuberosum L.). Lustrous needles, melting at 235°. A very weak base, somewhat poisonous. Contains no methoxyl, but six hydroxyls. Hydrolysis with dilute acids gives rise to sugars and solanidine, C4iH7jNOa. Solanidine is also found with solanine in the plant. Solanine as ordinarily obtained is probably a mixture of both these alka- loids. INDEX. PAOB Abrotine 490 Acetylcmchonine 339 Acetylharmaline 396 Acetylmetanicotine 161 Achilleine 489 Achilletine 498 Acolyctine 404, 407 Aconelline 403 Aconine 402, 403 Aconitic add 407 Aconitine 400 Acridic add 104 Acridine 104 Adenine 445 Alanine 460 Alcamines of the pyridine se- Aries 49 Aldehydine 43 Alkines 49 Allantoin 448 Allocinchonine 340 Allylpyridine 133 Alstonine 491 Amanitine 470 Amidoapodnchene 359 Amidobutyric add 28 Amidopropylvaleraldehyde 129 Amidopyridincs 17 Amidoquinoline 88 Amidovaleraldehyde (9) 27 Amidovaleric add 28 Andirine 463 Angelic add 411 Angeline. 463 PA6B Anhaline 487 Anhalonidine 487 Anhalonine 487 Anhydroberberilic add 323 Anhydroecgonine 242 Anhydrolupinine 185 Apoaconitine 401 Apoatropine 190 Apodnchene 358 Apodndionidine 366 Apodndionine 340 Apocodeine 270 Apoharmine 398 Apojapaconine 407 Apojapbenzaconine 407 Apomorphine 270 Apophyllenic add 299 Apopseudaconine 405 Apopseudaconitine 405 Apoquinamine 372 Apoquinene 376 Apoquinidine 378 Apoquinine 371 Arecaidine 152 Arecaine 156 Arecoline 154 Arginine .465 Aribine 492 Ariane 379 Artarine 490 Asparagine 453 Aspartic add 452 Aspidosamine 491 Aspidospermatine 491 495 496 INDEX. PAOB Aspidospenmne 491 Atisiiie 407 Atrolactic add 201 Atrolactyltropeine 228 Atropamine 194 Atropic add 199 Atropine 189 Atropyltropeinc 228 Atrosdne 196 Azoconhydrine 130 Bebeerine 488 Belladonnine 196 Benzoyldnchonioe 339 Benzoylconine 130 Benzoylecgonine 239 Benzoylmetanicotine 161 Benzoylpiperidine 27 Benzoylpseudotropeine 252 Benzoyltropeine 227 BenzylanthraniUc add 80 Benzylidene quinaldine 92 Berbamine 330 Berberal 323 Berberic add 322 Berberilic add 323 Berberinal 328 Berberine 320 Berberinium hydroxide 328 Berberonic add 71 Berilic add 323 Betaine 475 Betaine^of the pyridine series. . 73 Bilineurine 470 Bromamylamine (u)) 26 Bromcarpinic add 173 Broinconine 1 29 Brompyridine 15 Bromtarconine 301 Bromticonine 164 Bruddine 391 Brudne 391 Bnidnic add 392 Bulbocapnine 335 Butyrylbutyric add 129 Buxine 489 PAGE Cacostrydinine. 387 Caffearine 487 Caffeine. 428 Canadine 328 Carbodndiomeronic adds. 67 Carbodinicotinic add 70 Carboisodndiomeronic adds. . . 68 Carbolutidinic add 71 Carbostyril 87 Gamine 446 Carpafne 487 Cephfleline 493 Cevadic add 410 Ccvadilline : 409 Cevadine 410 Cevilline 414 Cevine 410 Chairamidine 379 Chairamine 379 Chelerythrine 490 Chelidamic add 21 Chelidonic add 20 Chelidonine 490 Chloramylamine (<u) 26 Chlorcaffeinc 431 Chlorcodide 270 Chlorconine 129 Chlorguanine 445 Chlorpiperidine 23 Chlorpyridines 15 Chlortheophylline 440 Chlortropic add 202 Cholestol 338 Choline 470 Chrysanthemine 487 Cinchamidine 370 Cinchene 35^ Cinchene dibromide 357 Cinchocerotine 338 Cinchol 338 Cincholoipone 346 Cincholoiponic add 347 Cinchomeronic add 62 Cinchonamine 370 Cinchonidne 340 Cinchonidine 340, 366 INDEX. 497 PAGE Cinchonidine (/9) 366 Cinchonidine (j) 366 Cinchonidine chloride 367 Cinchomfine 344 Cinchonigine 340 Cinchoniline 340 Cinchonine 339 Cinchonine chloride ^-^ 356 Cinchoninic add 104* 344 Cinchotenidine 367 Cinchotenine 343 Cinchotine 340, 368 Cinchotine sulphonic add 368 Cinchotoxine 353 Cinnamic add 238 Cinnamylcocaine 235 Cinnamylidene malonic add .... 238 Cinnamyltropeine 228 Citramide 158 Citrazinic add 157 Coca-ethyline 235 Conine (a) 251 Cocaine (Dextro) 248 Cocaine (Inactive) 249 Cocaine (L«vo) 233 Cocaines 232 Cocamine 236 Codamine 292 Codeine 268 Codethyline 271 Colchiceine 418 Colchicine 417 Colchidnic add 419 Colchisal 4x8 Collidine , 40 Comanic add 21 Comenamic add 21 Comenic add 21 Conchairamidine 379 Concbairamine 379 Cuncusconine 380 Conessine 492 Conhydrine 138 Coniceines 135 Conine 1 26 Conine (Dextro) 134 PAOB Conine (Inactive) 134 Conine (Lsvo) 134 Conquinamine 572 Conquinine 377 Convidne 493 Conylene 130 Conyhirethane 130 Conyrine 127 Corybulbine 334 Corycavamine 336 Corycavine 336 Corydaldine 333 Corydaline 332 Corydaloline 332 Corydine 336 Corytuberine 335 Cotarnic add 302 Cotarnine 298 Cotamone 301 Cotinine 163 Coumalic add 21 Cryptopine 295 Cupreine 371 Cupieol 338 Curare alkaloids 393 Curarine 382 Curine 382, 394 Cuscohygrine 256 Cusconine 380 Cusparidine 489 Cusparine 489 Cyanacetylpiperidine 27 Cycloheptadiene 224 Cycloheptadiene carboxylic add. 245 Cycloheptane 221 Cydoheptane carboxylic add. . . 246 Cycloheptanone 223 Cydoheptatriene 224 Cycloheptatriene carboxylic add 244 Cycloheptene 224 Cycloheptene carboxylic add. . . 246 Cytisine 179 Damasoenine 486 Behydrodnchene 357 498 INDEX. PAGB Dehydrodnchonine 344 Dehydrocorydaline 332 Dehydromorphine 267 Dehydrosparteine 183 Dekahydroquinoline 84 Delphinine 492 Dclphinoidine 492 Delphisine 492 Desoxycinchonidine. - 367 Desoxydnchonine 357 Desoxymorphine 267 Desoxystrychnine 388 Besoxyxanthine 426 Diacetylcupreine 371 Dibromapophylline 301 Dibromcotinine 163 Bibromisopilocarpine 174 Dibrompilocarpine 173 Dibrompropylmalonic ester. 256 Dibrompyridine 16 Dibromticonine 163 Dicarbodndiomeronic add 72 Dicarbodinicotinic add 73 Dichlorisoquinoline 109 Didnchonine 340 Dicodeine 270 Dicodeylmethane 269 Diconquinine 380 Diethanol amine. .^. 279 Diethanol methylamine 279 Diiiydroapoharmine 398 Dihydroarecaidine 153 Dihydrodnchene • 369 Dihydrodnchonine 341 Dihydroharmaline 396 Dihydroisoquinoline 303 Dihydronicotine 161 Dihydronicotyrine 168 Dihydroquinine 374 Dihydrosparteine 183 Dihydrostrychnine 387 Dihydrostrychnoline 389 Dihydroxytropidine 206 Dimethoxylisoquinoline 1 1 1 Dimethoxylisoquinoline carbox- ylic add& 1 1 1 PAGB Dimethoxyphenanthreiie 275 Dimethylamidocydoheptadiene. 225 Dixnethylamine 485 Dimethyldnchonine 352 Dixnethylcolchidnic add. 419 Dimethylconine 131 Dimethylcytisiiie 180 Dimethylglyoxaline 175 Dimethylnicotinic add 68 Dimethylnornarcotine 296 Dimethyloxyethylamiiie. 273, 278 Dimethylpiperidine 29 Dimethylpyridines. 39 Dimethylstrychnine 386 Dimethyliiric Sidd 439 Dinicotinic add 64 Dinitrodioxyquinoline 387 Dinitrostrychol 387 Dinitrostrychol carboxylic add. 386 Dioxyberberine 323 Dioxyphenatithiene 274 Dioxysparteine 183 Dipicolinic add 65 Dipiperidyl (a^ 78 Dipiperidyls 78 Dipyridyls 76 Diquinidine 380 Ditalne 491 Ditamine 491 Ecboline 494 Ecgonine (a) 250 Ecgonine (Dextro) 248 Ecgonine (Inactive) 249 Ecgonine (Laevo) 239 Echitamine 491 Echitenine 492 Emetine 493 Ephedrine 486 Ergotinine 494 Erythrophleic add 493 Erythrophle'ine 493 Eserine 488 Ethanol dimethylamine 2S0 Ethylapodnchene 360 Ethylapodnchenic add 360 INDEX, 499 PAGB Ethylcyclopentane carboxylic add 246 Ethylhomoapocinchenic add. 361 Ethylpiperidines 38 Ethylpiperidyl alcamine 54 Ethylpyridines 37 Ethylpyridyl alcamine 54 Eucaine 251 Euphthalmine 230 Ftunarine 490 Galipidine 489 Galipine 489 Geissospennine 489 Gelsemine 493 Gelseminine 493 Geoffroyine 463 Glutamine 459 Glutaminic add 457 Glyoxaline 175 Gnoscopine 311 Granatanine 260 Granatoline 260 Granatone 261 Guanine 443 Guvadne 155 Harmaline 395 HarmaloL 396 Hannine 397 Harminic add 398 Harmol 398 Harmolic add 398 Hemipinic add 306 Hexaliydronicotine 161 Hexahydroquinoline 84 Histidine 468 Homarecoline 155 Homatropine 227 Homoapodnchene 360 Homocaffeine 436 Homochelidonines 490 Homodnchonidine 366 Homodnchonine 340 Homonarceine 312 PAGB Homonicotinic add. PAGB Isaconitine 404 Isatropic acid. 191 IsocarbostyriL no Isodnchotneronic add 65 Isocinchonidixie 366 Isocinchonine 340 Isocodcine 269 Isoconine 134 Isocopellidioe 44 Isocorybulbine 335 Isodimethylstiychnine 387 Isomethylstrychmne 387 Isomorphine 267 Isomuscarine 475 Isonarcotine 298 Isonicotine 78 Isonicotinic add 59 Isonipecotinic add 61 Isoi)elletierine 258 Isophenylacetic add 247 Isopilocarpine 173 Isopropylpyridincs. 41 Isoquinoiine 107 Isoscopolamine 197 Isostrydminic add 387 Jaborandine 171 Jaborine 178 Jambosine 486 Japaconine 406 Japaconitine 406 Japbenzaconine 406 Jervic add. . , 1 415 Jervine 415 Kynurine 87, 346 Lactyltropeine 228 Lanthopine 294 Laudanidinc 293 Laudanine 292 Laudanosine 293 Ledthins 471 Lepidine 93 Lepidinic add 94 Leucine 464 PAGB Lcucol 5, 79 Loiponic add 347 Lophophorine 487 Loxopterygine 491 Lupanine (Dextro) 186 Lupanine (Inactive) 187 Lupetidine 38 Lupetidyl alcamine 53 Lupinic add 185 Lupinidine 185 Lupinioe 184 Lutidines 37 Lutidinic add 64 Lutidyl alcamine 53 Lycaconine 407 Lycaconitine 407 Lycoctonic add 407 Lycoctonine 407 Lycopodine 494 Lysine 467 Madeyine 295 Matrine 488 Meconidine 294 Meconic add 20 Meconine ' 297, 308 Meconinic add 308 Meroquinene 349 Metahemipinic add 288 Metanicotine 160 Metatropine 208 3-Methoxy-4-€WXtoxyphenanthni- quinone; 275 Methoxycaffeine. . . . .' 431 Methoxylepidine 95 3-Methoxy-4-ox3rphenanthrene. . 276 3 -Methoxy -4 -oxyphenanthrene- 9-carboxylic add 275 Methoxyphtbalic add. 285 Methoxyquinoline 87 Methylamylglyoxaline 175 Methyl betaine of dnchomeronic add 75 Methyl betaine of nicotinic add. . 7f Methyldnchonine 352 Methylcocalne 23^ INDEX. So» PAGB Methylcodefne 272 Methylcolchidne 419 Methylconine 135 Methylcytisinc 180 Methyldesoxydtichonidiae 367 Methyldesoxycinchonine 367 Methyldibrompyridine 207 Methylene dihydrobenzoic add. 246 Methylene dihydrobenzoL 212 Methylene dioxyisoquinoline. 112 Methylene dioxymethyltctiahy- droisoquinoline 113 ^-Methyl-a-ethylquinoline 93 Methyl- a^-ethylene piperidine. 53 Methyl-^-ethylpiperidine 52 Methylethylpyridines 42 Methylglyoxaline 175 Methylgranatanine 260 Methylgranatenine 260 Methylgranatic add 260 Methylgranatoline 260 Methylgranatonine 259 Methylharmaline 396 Methylhydrastinine 318 Methylisoquinoline iii Methylisostrychninic add 387 Methylmorphimethine (a). .272, 276 Methylmorphime thine {p) 276 Methylnaphthalane morpholine. 280 Methylnipecotinic add 153 Methylnornarcotine 296 Methylnoropianic add 305 Methyloxyethylamine 285 Methylpelletierine 259 »-Methyl-a-pipecoleinc 53 «-Methyl a-pipecoleine/9-alkine. 53 Methylpipecolyl alcamine 52 n-Methylpiperidine 29 Methylpyridines. 32 MethylpyrroHdme carboxylic add 255 Methylsinapic add 480 Methylstrychnine 385 n-Methylsucdnimide 220 fi-Methyltetrahydronicotinic add 60 Methyltropidine 206 PAGE Methyltropine (a) 204 Methyltropine {p) 205 Methylvinyldiacetone amine 229 tr-Methylvinylpipcridine 52 Mezcaline 487 Monobromticonine 164 Morphenol 276 Morphenol methyl ester 276 Morphidine 272 Morphine 266 Morphci 273 Morphol quinone 273 Morpholine 278 Morphothebalne 283 Muscarine 473 Mycoctonine 407 Myrosin 482 Nandinine 329 Napelline 404 Naphthalane morpholine 280 Naphthoquinolines 57, 58 Narceine 311 Narcotine 296 Neminc 473 Nicoteine 169 Nicotelline !. 169 Nicotimine 169 Nicotidine 78 Nicotine (Inactive) 159 Nicotine (Laevo) 164 Nicotinic add 57, 162 Nicotyrine 63 Nipecotinic add 61 Niqnine 375 Nitroapodnchene 359 Nitrodioxyquinoline 345 Nitroharmaline 396 Nitroharmine 396 Nitroisovanillin 275 Nitrosoconine 130 Nitrovanillin. 274 Norecgonine 240 Norhydrotropidine 208 Normetahemipinic add 319 Nomarcotine 296 502 INDEX, PAGE Noropianic add 305 Noroxyhydrastinine 324 Nortropinone 218 Noryohimbic add 492 Nupharine 489 Octohydronicotine 161 Opianic add 297, 305 Opium 264 Omitliine 466 Osdne 230 Oxazine 278 Oxyacanthine 329 Oxyberberine 323 Oxycaffeine 431 Oxydnchonines 344 Oxycotamine 304 Oxycytisine 180 Oxydichlorisoquinoline 108 Oxydimorphine 267 Oxyetbyldimethylamine 278 Oxyethylpiperonylic add. .... 325 Oxyethylveratric add 334 Oxyguanine 444 Oxyhydrastinine 317 Oxymorphine 267 Oxynarcotine 311 Oxynicotine 163 Oxyphenylquinolines 99 Oxypyridines 18 Oxyquinolines 86 Oxysparteine 183 Oxystrychnine 383 Oxysuberane carboxylic add. 246 Oxytoluyltropeine 227 Papaveraldine 290 Papaveraniine 295 Papaveric add 290 Papaverine 286 Papaverinol 291 Papaveroline 287 Paramorphine 283 Paratropine 52 Paridne 488 Parvtdine 32 PAGB Paudne 495 Paytamine 491 Pajrtine 491 Pelletierine 258 Pellotine 487 Pentaraethylene diamine 26 Pereirine 489 Phenanthrene 272 Phenanthrotine 77 Phenmoqjholine 279 Phenol quinolines 99 Phenylalanine 461 Phenylglyoxylic add 261 Phenylpyridine 57 Phenylpyridine dicarboxylic add 57 Phenylquinaldic add 98 Phenylquinaldine 98 Phenylquinolines 96 Ph3rsostigmine 48S Picolines. 