1944 POWER ANb ROGERSON!CCVL-The Constituents of Leptandra.By FREDERICK BELDING POWER and HAROLD ROGERSON.UNDER the title of (( lept,andra,” the Pharmacopaia of the UnitedStates recognises the dried rhizome and roots of Veronica virginica,Linn6 (Leptandra virginica, Nuttall), a plant which is indigenousto the greater part of North America. The above-mentionedunderground portion of the plant is used medicinally, and the cruderesinous material obtained therefrom is one of the products to whichthe name “ leptandrin ” has been assigned.The first chemical examination of (‘ leptandra ” appears to havebeen that recorded by E. S. Wayne (Proc. Amer. Pharm. Assoc.,1856, p. 34), who stated that, besides essential oil, bitter extractive,tannin, gum, and resin, it contains a crystalline, bitter substanceTHE CONSTITIJENTS OF LEPTANDRA. 1945which separated from the ethereal solution in needles.This sub-stance, although not further characterised, was considered to repre-sent the active principle of the drug, and for it the name “lep-tziidrin ” has since been proposed. The same investigator (Amer.J . Plzarrn., 1859, 31, 557) also observed the presence of “ asaccharine principle having the properties of mannite.” It wassubsequently indicated by F. F. Mayer (Amer. J . Pharrn., 1863,35, 298), and more recently by J. U. Lloyd (Proc. Amer. Pharm.Assoc., 1880, 28, 421), that the bitter principle of the drug is aglucoside, although no definite substance of this class had actuallybeen isolated. Steinmann (Amel.. J .Pizurm., 1887, 59, 229) statesthat he obtained the bitter principle in crystals of a pale lemon-yellow colour, but they yielded no dextrose when boiled with dilutesulphuric acid, and their solution gave no precipitate with theusual alkaloid reagents.It will be apparent from the brief review of the literature givenabove that, with the exception of the recorded presence of mannitol,nothing of a, very definite nature has up to the present been knownrespecting the constituents of ‘( leptandra.” It was thereforedeemed of interest t o subject it to a complete examination, andthe results are embodied in the present communication.EXPERIMENTAL.The material employed for this investigation consisted of a goodquality of commercial “leptandra,” which conformed in its charactersto the description given of the latter in the United StatesPliarmacopa4a.A small portion (10 grams) of the material was first tested for analkaloid, but the reactions were so slight as to indicate the presenceof not more than traces of such a substance.Twenty grams of the ground material were successively extractedin a Soxhlet apparatus with various solvents, when the followingamounts of extract, dried at looo, were obtained:Petroleum (b.p. 35-50“) extracted 0.11 gram -T 0.65 per cent,Ether ,, 0.56 ,, = 2’80 ,,Chloroform ,) 1-00 ,, = 5-00 ,,Ethyl acetate ,, 0 65 ,) = 3.25 ),Alcohol ,, 2.95 ,, =14.75 ,, - -Total 5 -27 grams = 26 *35 per cent.For the purpose of a complete examination, a quantity (55.56kilograms) of the ground material was extracted by continuouspercolation with hot alcohol. After the removal of the greaterportion of the alcohol, a viscid, dark-coloured extract was obtained,amounting to 19.79 kilograms.VOL.XCVII. 6 1046 POWER AND ROGEHSON :Distillation of the Bxtract with Steam. Separation of anE'ssentid Oil.A quantity (2 kilograms) of the above-mentioned extract wasmixed with water, and steam passed through the mixture forseveral hours. The distillate, which amounted to about 6 litres,contained some oily drops floating on the surface. It was thoroughlyextracted with ether, the ethereal liquid being dried and the solventremoved, when 0.9 gram of an essential oil was obtained. Theyield of the latter was thus equivalent to 0.16 per cent. of theweight of the drug.This essential oil, when distilled underdiminished pressure, passed over between 120° and 160°/25 mm.It was a dark brown, mobile liquid, possessing a strong, persistentodour, and gave no coloration with ferric chloride.Non-volutile Constituents of the Extract.After the distillation of the extract with steam, as abovedescribed, there remained in the distillation flask a dark-coloured,aqueous liquid (A), and a quantity of a dark brown resin (B).These products, when cold, were separated by filtration, and theresin repeatedly washed with hot water until nothing further wasremoved, the washings being added to the aqueous liquid.Examination of the Aqueous Liquid (A).Isolation of 3 : 4-Bimethoxycinnamic Acid,C,H,(OMe),*CH :CH*CO,H.The aqueous liquid was repeatedly extracted with ether, and thecombined ethereal extracts evaporated to a small volume.Oncooling, a quantity (5.0 grams) of a crystalline substance separated.This was removed by filtration, dried, and recrystallised from water,when it separated in yellow needles, melting at about 170°, butafter repeated crystallisation from absolute alcohol it was obtainedin large, colourless needles, melting at 180-181O. (Found, C = 63.4 ;H = 5-9 ; OMe= 29.2. Cdc., C = 63-5 ; H = 5.8 ; OMe = 29.8 percent.)The substance was found to be an acid, and is seen to agree in itscharacters and composition with 3 : 4-dimethoxycinnamic acid,C,H,(OMe),*CH:CH*C"02H. When mixed with a portion of thelatter, as obtained by the methylation of ferulic acid (Trans., 1907,91, 8931, the melting point w a unchanged. Furtiher confirmationof the identity of the acid was obtained by t b preparation of itsmethyl ester, which separated from absolute alcohol in smallprisms, melting at 64O.So far as known t o us, this is the firsTHE CONSTITUENTS OF LEPTANDRI. 1947instance in which 3 : 4-dimethoxycinnamic acid has been observedto occur in nature.The ethereal liquid from which the above-described acid had beenseparated was diluted somewhat, and then shaken with successiveportions of aqueous ammonium carbonate. On acidifying thealkaline liquids, a solid substance was p,recipitated, which waslikewise found to consist. of 3 : 4-dimethoxycinnamic acid.Thetotal amount of this acid obtained from 2 kilograms of the originalalcoholic extract was 12.0 grams, and was thus equivalent to about0.2 per cent. of the weight of the drug.The ethereal liquid was subsequently shaken with a solution ofsodium carbonate, which, however, removed nothing. It was thentreated with a 10 per cent. solution of sodium hydroxide, when aquantity of resinous material was removed, but from which nothingdefinite could be isolated. On finally evaporating the ether, onlya small amount of a yellow, amorphous product: was obtained.The original aqueous liquid (A), which had been extracted withether as above described, was thoroughly shaken with successiveportions of amyl alcohol. These liquids were then united, washedrepeatedly with water, and concentrated under diminished pressuret o a small volume, when, on cooling, a considerable quantity of alight brown, amorphous product separated.After removing theamyl alcohol as completely as possible, the entire amount of thisproduct was dissolved in alcohol, and the solution poured into alarge volume of water. The precipitate thus produced was collected,washed, and dried, when it could be reduced to a brown powder,but all attempts to obtain it in a crystalline state were unsuccessful,It amounted to 90 grams, or 1.6 per cent. of t.he weight of drugemployed.The abovedescribed product possessed an intensely bitter andnauseous taste. It was readily soluble in alcohol, but very sparinglyso in water, even on boiling.Although the very dilute aqueoussolution frothed strongly on agitat,ion, the substance appeared topossess otherwise none of the characters of the saponins, and it wasnot sternutatory.In order. to obtain some further information respecting thecharacter of the above-described product, a quantity (10 grams) ofit was heated with 1000 C.C. of 2 per cent. aqueous sulphuric acidfor about four hours, when, on cooling, a hard, black, resinous massseparated. The liquid was then distilled in a current of steam,the distillate extracted with ether, and the ethereal liquid shakenwith a solution of sodium carbonate. On acidifying the alkalineliquid, again extracting with ether, and removing the solvent, a6 M 1948 POWER AND ROGERSON:small amount of an acid was obtained, which, on cryst,allising fromwater, separated in leaflets, melting at 131-133O.This acidyielded benzaIdehyde on oxidation, and was identified as cinnamicacid. The ethereal liquid which had been extracted with alkali wasfinally evaporated, but it yielded only a trace of a deep yellow oil.The aqueous, acid liquid remaining after the distillation withsteam, as above described, was separated from the hard, black,resinous mass, which weighed 5.5 grams, and shaken with ether, theethereal liquid being subsequently extracted with a solution ofammonium carbonate. On acidifying the alkaline liquid, againextracting with ether, and removing the solvent, about 0.3 gramof a crystalline product was obtained, which was found to consistof a mixture of acids.The ethereal liquid which had beenextracted with alkali was finally evaporated, but it yielded only asmall amount of a yellow oil, which gave a green coloration withferric chloride.After extracting the above-mentioned aqueous, acid liquid withether, it was treated with barium hydroxide for the removal ofthe sulphuric acid. The filtered liquid readily reduced Fehling’ssolution, but no crystalline osazone could be prepared from it.From the above results it was evident that the bitter, amorphousproduct, which had been obtained by extracting the originalaqueous liquid with amyl alcohol, was of a complex nature, andthat not more than a small proportion of it could have beenglucosidic. It was, moreover, apparent that the acids which ityielded by treatment with dilute sulphuric acid were present in theform of esters, inasmuch as on heating the product with aqueoussodium hydroxide a similar mixture of acids was obtained, and inbetter yield. This mixture of acids was found on examination toconsist chiefly of pmethoxycinnamic acid, together with smalleramounts of cinnamic acid and another compound which could notbe identified.The original aqueous liquid, after being extracted with amylalcohol as above described, was concentrated somewhat, and treatedwith a slight, excess of a solution of basic lead acetate.A copiousbrown precipitate was thus produced, which ww collected, wellwashed with water, then suspended in water, decomposed byhydrogen sulphide, and the mixture filtered.The filtrate, whenconcentrated, was dark reddish-brown, and appeared to containonly tannic and colouring matter.The liquid from the basic lead acetate precipitate was treatedwith hydrogen sulphide for the removal of the lead, and the filteredliquid concentrated to a small bulk. To the syrup thus obtaineTHE CONSTlTUENTS OF LEPTANDRA. 1949a large volume of alcohol was added, when a quantity of acrystalline substance was deposited, which was collected, washedwith a little alcohol, and dried. The liquid from which this crys-talline substance had been separated was deprived of alcohol, andevaporated to the consistency of a syrup. It evident,ly contained alarge amount of a sugar, since it readily reduced Fehling's solution,and yielded d-phenylghcosazone, melting at 209-211O.Isolation of d-Nannito2.The crystalline substance above described, which amounted to120 grams, or 2.14 per cent. of the weight of the drug, was r ecrystallised from alcohol, when it separated in needles, melting a t165--166O, and proved to be d-mannitol.(Found, C=39.5 j H= 7.8.Calc., C=396; H=7*7 per cent.)Further confirmation of the identity of the above-describedsubstance with mannitol was obtained by the formation of its acetyland benzoyl derivatives.On heating a little of the substance with acetic anhydride, aproduct was obtained which, when crystallised from absolutealcohol, separated in octahedra, melting at 122-124O, and consistedof the hex%acetyl derivative of mannitol.Another portion of the substance was benzoylated by theSchotten-Baumann method, as employed by Panormoff (J.Russ.Phys. Chem. SOC., 1891, 23, 375), when a product was obtainedwhich w a soluble in chloroform, but, on the removal of the solvent,formed a syrup. On dissolving this, however, in a small volume ofether, it yielded a mass of needle-shaped crystals, which melted a t149O, and after recrystallisation from a mixture of ethyl acetateand alcohol, or from acetic anhydride, the melting point remainedunchanged. (Found, C = 71.3 ; H = 4.9. Calc., C = 71.4 ; H = 4-7per cent.)This substance is thus seen to be hexabenzoylmannitol,C6H806(CO*C6H5)6, the melting point of which has been 'given as149O by Skraup (Monatsh., 1889, 10, 389) and by Panormoff (Zoc.c i t .) , but was incorrectly recorded by Stohmann, Rodatz, andHerzberg ( J . pr. Chem., 1887, [ii], 36, 354) as 124-125O.The optical rotatory power of hexabenzoylmannitol does notappear to have previously been recorded, and this was thereforedetermined, with the following result :0.4238, made up to 20 C.C. with chloroform, gave a, +2O9f in a2-dcm. tube, whence [a], '+ 50-7O.If the benzoylation of mannitol is conducted in the usual manner,by adding the benzoyl chloride in small quantities at a time, adibenzoyl derivative, C6H1206(CO*C6H,),, is obtained. This is ver1950 POWER AND ROQERSON:sparingry soluble in the usual organic solvents, and crystallises insmall, prismatic needles, which melt at 178-180°. (Found,C=61*0; H=5*8.0.3410, made up to 20 C.C.with pyridine, gave a, +Oo22/ in a,2-dcm. tube, whence [a], + 10'7O.Dibenzoylmannitol has previously been obtained by Einhorn andHollandt (9nnaZen, 1898, 301, l02), who recorded ih meltingpoint as 178O. On adding an excess of benzoyl chloride to a hotsolution of mannitol in pyridine, according to the method of thelasbmentioned investigators, a crystalline substance began toseparate at once, which was evidently the dibenzoyl derivative.When, however, the liquid was heated a little longer, a vigorousreaction ensued, which soon subsided, and a perfectly clear solutionwas obtained. The product was then poured into water andextracted with ether, when a substance was obtained which melteda t 149O, and proved to be hexabenzoylmannitol.Calc., C=61.5; H=5.6 per cent.)Examination of the Resin (B).This was a dark brown, brittle mass, and amounted to abouti350 grams, being thus equivalent to 6.2 per cent.of the drug. Itwas dissolved in alcohol, mixed with purified sawdust, and themixture successively extracted in a Soxhlet apparatus' with lightpetroleum (b. p. 35-50°), ether, chloroform, ethyl acetate, andalcohol.Petroleum Extract of the Resin.Theextract was dissolved in ether, and the ethereal solution shakenwith aqueous ammonium carbonate, which, however, removed onlya small amount of resinous material, together with a trace of3 : 4-dimethoxycinnamic acid. The ethereal solution was thenshaken with aqueous potassium carbonate, and the alkaline liquidacidified, when a quantity of black, tarry material was precipitated.This was distilled several times under diminished pressure, when aproduct was finally obtained which passed over between 220° and240°/15 mm.as a light yellow oil, and partly solidified on cooling.The free acids thus obtained amounted to 3.7 grams, and wereexamined together with the combined acids which will subsequentlybe described.After treatment with potassium carbonate, as above described,the ethereal solution was shaken with aqueous potassium hydroxide,which, however, removed nothing. On finally evaporating the ether,a residue was obtained, which was hydrolysed by heating with analcoholic solution of potassium hydroxide. The alcohol wm thenThis was a dark brown mass, amounting to 24.5 gramsTHE CONSTITUENTS OF LEPTAKDRA. 1951removed, and the cooled, aqueous, alkaline liquid extracted withether, the ethereal liquid being dried and the solvent evaporated.On dissolving the residue in alcohol, a small quantity of a solidseparated, which, when recrystallised from ethyl acetate, melted at62-65O, and was found to consist of a hydrocarbon and an alcohol,but the amount was too small tor permit of their separation.Zsolation of a Phytosterol, Verosterol, C2,H,,0,H,0;The alcoholic filtrate from the above-mentioned solid was con-centrated to a small bulk, when, after two or three days, a quantityof a crystalline substance separated. This was collected, washed,and recrystallised from a mixture of ethyl acetate and dilutealcohol, when it separated in flat needles, melting a t 135--136O,and gave the colour reactions of the phytosterols :0.2500, on heating at l l O o , lost 0.0126 H20.0.1230 * gave 0.3764 CO, and 0.1360 H,O.H;O=5*0.C=83*5; H=12*3.C27H,,0,H20 requires H20 =4*5 per cent.C,,H,,O requires C=83*9; H=11.9 per cent.A determination of its optical rotatory power gave the followingresult :0*2374,* made up to 20 C.C.with chloroform, gave a, -0O47' in a2-dcm. tube, whence [uJD -33.0'.A small amount of the phytosterol waa converted into its acetate,which separated from acetic anhydride in flat needles, melting atThe above-described phytosterol evidently represents a memberof this class of substances which is widely distributed in nature,and compounds possessing practically the same physical charactershave previously been obtained in these laboratories from varioussources, such as olive bark, wild cherry bark, and jalap (Trans.,1908, 93, 909; 1909, 95, 246; J .Amer. Chenz. SOC., 1910, 32, 87;compare also Menozzi and Moreschi, Atti R . Accad. Lincei, 1910,[v], 19, i, 187). I n view of these facts, and in order to distinguishthe abovedescribed phytosterol from sitosterol, which differs bythe higher melting point of its acetate (Monutsh., 1897, 18, 551),it would appear desirable to assign to it a specific name. It istherefore proposed to designate it verosterol, with reference t o thegeneric name of the plant, Veronica, from which it has now beenobtained.Identification of the Fatty Acids.The alkaline liquid, which had been extracted with ether asabove described, was acidified, and the liberated fatty acids collected,* Anhydrous substance.119-120'1952 POWER AND ROGERSON:dried, and distilled under diminished pressure, when they passedover between 220° and 250°/15 mm. as a pale yellow oil.Theacids t.hus obtained, which amounted to 4.2 grams, were mixed withthe previously mentioned portion of acids present in the free state,and the whole converted into their lead sa.lts, the latter being thendigested with ether, when a portion was dissolved. Both thesoluble and insoluble portions were decomposed by hydrochloric acid,and the regenerated fatty acids purified by distillation underdiminished pressure. The soluble portion of the lead salts yielded4.2 grams of liquid acids, whilst, the insoluble portion gave 3.3 gramsof solid acids.The Liquid A cids.-These acids, when distilled under diminishedpressure, passed over between 215O and 235O/15 mm.i19 a yellowoil. An analysis and a determination of the constants gave thefollowing results :0.1738 gave 0.4842 CO, and 0*€788 H,O.0.3788 absorbed 0-4872 iodine.0.1540 neutralised 0.0307 EOH.C = 76.0 ; H = 11.4.Iodine value = 128.6.Neutralisation value = 199.3.C18H3402 requires C = 76.6 ; H= 12.1 per cent. Iodine value= 90.1 ;C,,H,O, requires C = 77.1 ; H = 11.4 per cent. Iodine value = 181.4 ;It is evident from the above results that the liquid acids con-sisted of a mixture of oleic and linolic acids.The Solid A cids.-These acids, after being again distilled underdiminished pressure, were 'crystallised twice from ethyl acetate,when they melted at 54-56O:Neutralisation value = 198.9.Neutralisation value = 200.4.0.1512 gave 0-4190 CO, and 0.1728 H,O.C=75-6; H=12.7.0.2864 neutralised 0.0590 KOH. Neutralisation value = 206.C,,H3,O, requires C = 75.0 ; H = 12.5 per cent.Neutralisation value= 219.1.C,,H3,02 requires C = 76.1 ; H = 12-7 per cent.Neutralisation value = 197.5.These results indicate that the solid acids consisted of a mixtureof palmitic and stearic acids in about equal proportions.Ethereal Extract of the Resin.During the extraction of the resin with ether a quantity of asparingly soluble, yellowish-brown substance was deposited, andwhen the extraction was complete this wits collected, washed withether, and dried, when it was found to weigh 5 grams.It wasentirely amorphous, and proved t o be similar in character to theproduct extracted from the original aqueous liquid by amyl alcoholTHE CONS’L‘I‘I’UENTS OF LEPTAXDRA. 1953which has already been described. On heat,ing with aqueoussodium hydroxide, it yielded pmethoxycinnamic acid, which wassubsequently obtained in larger amount from the chloroformextract of the resin.The portion of extract which was more readily soluble in etherconsisted of a dark resinous mass, amounting to 95 grams. Itwas thoroughly examined, but nothing except a small quantity of3 : 4-diinethoxycinnamic acid could be isolated from it.Chloroform Extract of the Resin.This was a dark-coloured resinous mass, weighing 135 grams.Itcould easily be reduced to a fine powder, which was tasteless. Thechloroform solution of the resin was shaken with aqueous ammoniumcarbonate, when a small quantity of 3 : 4-dimethoxycinnamic acidwas removed. The liquid was then shaken with it solution ofsodium carbonabe, but only a small amount of a resinous productwas obtained.Isolation of p-Methoxycinnamic A cid, OMe*C,H,*CH:CH*C02H.After treating the chloroform liquid with the alkaline carbonates,as above described, it was shaken with successive portions of it10 per cent. solution of sodium hydroxide. These liquids wereunited and acidified, when a large quantity of a black, resinousproduct was precipitated.This resinous product was then treatedwith chloroform, in which it only partly dissolved. The chloroformsolution was shaken with aqueous sodium carbonate, and thealkaline liquid acidified, when a crystalline precipitate was obtained.It was thus evident that on shaking the original chloroform liquidwith alkali hydroxide, some constituent of it had been hydrolysed.The crystalline precipitate was collected, washed, and dried, whenit amounted to 14 grams. By fractional crystallisation from ethylacetate, it was found t o consist of a mixture of 3 : 4-dimethoxy-cinnamic acid and an acid which separated in iridescent, prismaticneedles. The lakter melted a t 170°, assuming a (( liquid-crystalline ”phase, which persisted until the temperature of 181-182O wasreached, when it passed into the ordinary liquid state.The“crystalline” character of the liquid between 170° and 181O wasconfirmed by observing it through crossed Nicol’s prisms. The last-mentioned acid was analysed. (Found, C = 67.3 ; H = 5.8 ;OMe = 17.3.In order further to characterise this acid, its methyl ester wasprepared. This was accomplished by boiling a solution of the acidin methyl alcohol .with a few drops of concentrated sulphuric acidCalc., C = 67.4 ; H = 5.6 ; OMe= 17.4 per cent.1954 POWER AND ROCIERSOK:for about two hours on the water-bath. The product so obtainedwas recrystallised from absolute alcohol, when it separated in flatneedles, melting at 88-90°.The above results render it evident that the subst’ance underexamination was pmethoxycinnamic acid, which appears only oncepreviously to have been observed to occur in nature.I n the formof its ethyl ester, it was found by van Romburgh t o be the chiefconstituent of the essential oil of Xaernpf eria galanga, Linn6 (Proc.K . Akad. Wetensch. Amsterdam, 1900, 3, 38; 1902, 4, 618;Schimmel’s Bericht, Oct., 1900, p. 37, and April, 1903, p. 38).As it appears not to have previously been recorded thatp-methoxycinnamic acid shows, on heating, a (( liquid-crystalline ”phase, it was deemed desirable to confirm this observation by meansof the synthetically prepared acid. For this purpose a smallquantity of p-coumaric acid was methylated by means of methylsulphate, and the product recrystallised from ethyl acetate, whenit separated in prismatic needles, melting to the ‘( liquid-crystalline ”phase at 170°, and then passing to the ordinary liquid state a t181-182O.A mixture of the naturally-occurring and syntheticacids likewise showed exactly the same behaviour at the same tem-peratures, and their identity was therefore definitely established.The chloroform liquid from which the above acids had beenisolated was finally evaporated for the removal of the solvent. Aresinous product was thus obtained, from which, however, nothingcrystalline could be isolated.Et?bcyl Acetate and Alco?boZ Extracts of the Resh.These extracb were dark, resinous products, amounting to 77.5and 32.0 grams respectively. They were heated with a 5 per cent.solution of sulphuric acid in aqueous alcohol, but, with the exceptionof a, smsll quantity of sugar yielding d-phenylglucosazone (m. p.209-210°), nothing definite was obtained.Summary.The results of the present investigation may be summarised asThe material employed was commercial (‘ leptandra,” consisting.follows :of the rhizome and roots of Veronica virginica, Linn6 (Leptandrauirginica, Nuttall).An alcoholic extract of this material, when distilled with steam,yielded an amount of essential oil equivalent t,o 0.16 per cent.ofthe weight of the drug. This essential oil was a dark brow0 liquid,which distilled between 120° and 16Ooj25 mmTHE CONSTITUENTS OF LEPTANDRA. 1955The portion of the extract which was soluble in water contained3 : 4-dimethoxycinnamic acid, a quantity of mannitol, amounting to2-14 per cent.of the weight of the drug, and a sugar which yieldedd-phenyIglucosazone (m. p. 209-211°), together with some tannicand colouring matter. It yielded, furthermore, a quantity of abrown, amorphous product, which possessed an intensely bitter,nauseous taste, and amounted to 1.6 per cent. of the weight of thedrug. By the hydrolysis of this product there were obtained,besides resinous material, cinnamic and p-methoxycinnamic acids.The portion of the extract which was insoluble in water consistedchiefly of a dark brown resin, which amounted to 6.2 per cent. ofthe weight of the drug. From this resin the following substanceswere obtained: A phytosterol, C2,H,,0 (m. p.135-136O;[aID -33*Oo), which it is proposed to designate verosterol; a mix-ture of fatty acids, consisting apparently of oleic, linolic, palmitic,and stearic acids ; p-methoxycinnamic acid, which was present inthe form of an ester; and a very small amount of 3 : 4-dimethoxy-cinnamic acid, which had probably been occluded by the resin.It htts been observed that p-methoxycinnamic acid, when melted,passes into a, ‘‘ liquid-crystalline ” phase, which persists until atemperature of 181-182O is reached.It has not been possible to confirm the statement recorded inthe literature that leptandra ” contains a crystalline, bitterglucoside, designated as “ leptandrin,” to which its activity maybe attributed. Steinmann (Amer. J . Pharm., 1887, 59, 229)obtained from “leptandra,” in an amount of about 0.1 per cent.,a, crystalline, yellow substance, which possessed a, very bitter taste,and was found not to be a glucoside, although it was not furthercharacterised. From the method by which this substance wasisolated, itl appears highly probable that it consisted of 3 : 4-di-methoxycinnamic acid, contaminated with a little of the above-mentioned, bitter, amorphous product. The fact that an aqueoussolution of this product froths strongly on agitation has doubtlessled to the statement recorded in the literature that ((leptandra”contains saponin.Some tests with preparations of (‘ leptandra,” which were kindlyconducted for us by Dr. E. H. Dale, Director of the WellcomePhysiological Research Laboratories, led to the following conclusions.Both the crude resin and the bitter, amorphous product obtainedfrom the portion of the alcoholic extract which was soluble in waterwere administered by the mouth to dogs, in doses of 1 gram each,but without any visible effect The bitter, amorphous product wasalso tested on the mammal by intravenous injection, ,and on theisolated mammalian heart, but no characteristic action could b1956 MAY: AROMATIC ANTIMONY COMPOUNDS. PART I.observed. Although the total alcoholic extract of the drug, whengiven to a dog in doses of 5 grams, produced vomiting, this maybe attributed to its nauseous taste and irritant effect on the stomachrather than to any specific action.THE WELLCOME CHEMICAL RESEARCH LABORATORIES,LONDON, E.C