The Phenolic Substances of White Hellebore (Veratrum Grandiflorum Hoes. Fil). IV

Abstract

From the roots of Veratrum grandiflorum Loes. fil. have been obtained 2 phenolic substances, resveratrol, C14H12O3 (I), and hydroxyresveratrol, C14H12O4 (II), and in addition phytosterolin (III), m. 293-4° (acetate, C41H64O10, m. 171.5°; cf. Nakamura and Ichiba, C. A. 25, 2434) in yields of 0.07, 0.03 and 0.02%, resp., of the dried roots. I and II have been proved to be 3,5,4'-stilbenetriol and 3,5,2',4'-stilbenetetrol, resp. It is discussed whether the phenolic compound C14H12O3, m. 256°, isolated from the resin of rhubarb by Tutin and Clewer (C. A. 5, 3052) and considered by them to be a trihydroxydihydroanthracene, might also be a stilbene derivative I, II and III are isolated from the brown powder obtained by Saito and Suginome (C. A. 30, 5995.3) from the alc. extract of the roots after removal of the alkaloids by dilute AcOH. The brown powder is extracted 8 times with ether and the ether residue treated with light petroleum. For the separation of I, II and III the product obtained is again treated with ether which dissolves II. I and III are separated by boiling with 50% alc. whereby III remains undissolved. From the filtrate I crystallizes on cooling. The ether solution containing II is treated with 5% Na2CO3, the precipitate refluxed with dilute alc., the filtrate kept overnight, some separated I removed and the filtrate kept at room temperature for several days, when II seps. From the mother liquor some more II is isolated as acetate. I is also obtained by treating the brown powder with 2% NaOH, saturating the filtrate with CO2 and treating the precipitate with ether. I, already obtained by S. and S., crystals from 50% alc. and from H2O, m. 261°, absorption maximum at 361, 335, 302, 290 (weak) and 248 mμ in 0.005 and 0.0005 M absolute alc. solution I gives with FeCl3 a dark green color, with concentrated H2SO4 a carmine-red color which becomes yellow on dilution with the same acid; the solution of I in 2 N KOH is colored blood-red on addition of aqueous K3Fe(CN)6.Zn dust distillation of I yields PhOH. The triacetate (IV) of I, needles from MeOH and from EtOH, m. 114-16°. The spectrum of IV (absorption maximum at 327, 315, 290 (weak) and 240 (weak) mμ in 0.005 and 0.0005 M ether solution) is similar to that of stilbene. The tri-Me ether (V) of I, crystals from MeOH, m. 56-7°, b. 177-8° (in vacuo), absorption maximum at 338, 315, 290 (weak) and 242 mμ in 0.005 and 0.0005 M ether solution, is obtained from I with CH2N2 or by treating IV in MeOH with 50% KOH and Me2SO4 at 60°. V decolorizes KMnO4. CrO3 oxidizes V in hot glacial AcOH to p-MeOC6H4CO2H, in the cold to 3,5-(MeO)2C6H3CHO. By treating 0.5 g. V with Na and absolute alc. and brominating the reduction product in CS2, 0.5 g. of a dibromo-3,5,4'-trimethoxydiphenylethane (VI), needles from absolute alc., m. 133-4°, is formed. VI is also obtained synthetically in 0.27-g. yield by treating 3.0 g. 3,5-(HO)2C6H3CH2CO2H (VII) with 2.37 g. NaOH, 6 cc. H2O and 16.6 cc. Me2SO4, hydrolyzing the methylation product with 14 cc. 10% NaOH, whereby 2.15 g. 3,5-dimethoxyphenylacetic acid (VIII), prisms from H2O, m. 104-5°, is formed, heating 0.9 g. of the Na salt of VIII with 0.72 cc. anisaldehyde (IX) and 4.5 cc. Ac2O for 8 h. at 165-70°, heating 0.2 g. of the resulting 1.04 g. 3,5,4'-trimethoxystilbene-α-carboxylic acid, needles from alc., m. 182°, with 0.2 g. Naturkupfer C and 2 cc. quinoline at 205° and reducing and brominating the reaction product as in the case of V. In the course of unsuccessful attempts to synthesize V the following compounds have been prepared 3,5-Dimethoxyphenyl 4-methoxycinnamate(X), crystals from MeOH, m. 81-3°, is obtained from p-MeOC6H4CH:CHCOCl and 1,3,5-HO(MeO)2C6H3 in pyridine. When heated for 6 h. to 305-15° in a current of N or distilled with Naturkupfer C, X yields 4,4'-di-methoxystilbene, m. 209.5-10.5°, which has also been obtained by the condensation of IX with p-MeOC6H4CH2CO2H (XI). By heating a mixture of 0.8 g. 3,5-(MeO)2C6H3CHO and 0.8 g. XI for 8 h. in a sealed tube is obtained 0.2 g. of a compound C18H16O5, yellowish crystals from alc., m. 174°, insoluble in H2O and alkali, soluble in organic solvents with strong bluish violet fluorescence, showing absorption maximum at 392, 375, 350 (weak), 308, 300 (weak), 270 and 261 mμ in 0.0004 M absolute alc. solution, which might be a coumarin. II, plates with 2H2O from 30% alc. and from H2O, m. 199.5°, absorption maximum at 340, 320, 299 and 248 mμ in ether. II gives a brown color with FeCl3, a red color with H2SO4; HNO3 dissolves only a little, giving a yellow solution while the undissolved part becomes dark purple. II decolorizes KMnO4. It gives resorcinol on Zn dust distillation The tetraacetate (XII) of II, crystals from alc., m. 141-2°, gives with concentrated H2SO4 a yellow color which becomes reddish yellow on shaking. By oxidation with CrO3 in glacial AcOH, XII yields β-diacetylresorcylic acid. The tetrabenzoate (XIII) of II, crystals from Me2CO, m. 193.5°. XIII is oxidized by CrO3 in glacial AcOH to α-dibenzoylresorcylic acid, needles from glacial AcOH, m. 227° (identical with the compound obtained by benzoylation of α-resorcylic acid with BzCl and pyridine) and β-dibenzoylresorcylic acid, needles from glacial AcOH, m. 152° (identical with the benzoylation product of β-resorcylic acid). By methylating 1.12 g. II with Me2SO4 and aqueous NaOH, treating the oily tetra-Me ether formed with Na and absolute alc. and brominating the reduction product, 1.17 g. of a tribromo-3,5,2',4'-tetramethoxydiphenylethane (XIV), needles from absolute alc., m. 185-6°, is formed. XIV is also obtained synthetically by heating 1.0 g. of the Na salt of VIII with 1.0 g. 2,4-(MeO)2C6H3CHO and 6 cc. Ac2O, heating the resulting 3,5,2',4'-tetramethoxystilbene-α-carboxylic acid, crystals from alc., m. 181.5° (yield 0.47 g.), with Naturkupfer C and quinoline at 210° and subsequent reduction and bromination as above. By heating 0.55 g. of the Na salt of VII with 0.55 g. 2,4-(HO)2C6H3CHO and 3 cc. Ac2O for 8 h. at 165-75° is formed 1.34 g. of the lactone of 2'-hydroxy-3,5,4'-triacetoxystilbene-α-carboxylic acid, pale yellow needles from alc., m. 186-7°, easily soluble in CHCl3 and Me2CO with bluish violet fluorescence, insoluble in bicarbonate solution For the purpose of comparison the absorption maximum have been established in ether solution of 0.005 and 0.0005 M concentration for triphenylmethane at 304, 293, 281, 276 (weak), 270 and 264, for anthracene at 376, 371, 357, 350 (weak), 338, 335 (weak), 323, 308 and 295, for dihydroanthracene at 376, 371 (weak), 356, 354 (weak), 335 (weak), 334, 325, 308, 271, 264 and 252, for stilbene at 322, 308, 290 (weak) and 237, for 4-acetoxystilbene at 325, 312, 290 (weak) and 238 and for 4-hydroxystilbene at 336, 322, 290 (weak) and 242 mμ.