Perfamine — A new alkaloid from the seeds of Haplophyllum perforatum

Chemistry of Natural Compounds
1975.0

Abstract

Continuing an investigation of the neutral fraction of a chloroform extract of the seeds of Haplophyllum perforatum collected in the "Gallya-Aral" sovkhoz, Samarkand oblast, we chromatographed the mother liquors remaining after the separation of eudesmine and haplamine (main components of the neutral fraction). From ethereal eluates we obtained a new optically active base (I) called perfamine, with composition C15H19NO4, mp 164-165°C (ether-acetone), [α]D + 53.4 °, mol. wt. 313 (mass spectrometry). Perfamine is soluble in chloroform, less so in ethanol, methanol, acetone, ether, insoluble in water, dilute acids, alkalis; TLC (silica gel, toluene-ethyl acetate-formic acid 5:4:1) Rf 0.60, fluoresces dull green in UV, revealed by Dragendorff reagent. IR spectrum shows furan ring (3145, 3165 cm⁻¹) and conjugated carbonyl (1670 cm⁻¹). UV spectrum (λmax 215, 264.5, 272.5, 345 nm; log ε 4.30, 4.43, 4.43, 3.91; λmin 238, 290 nm; log ε 3.90, 3.69) differs from 4-methoxyfuranoquinoline and 4-methoxy-5,6,7,8-tetrahydrofuranoquinoline alkaloids, with 345 nm max due to dienone chromophore. NMR spectrum (CDCl3) has signals of 19 protons: two doublets (2.10, 3.88 ppm, 1H each, J=9 Hz, olefinic protons of dienonic ring A), two doublets (2.36, 2.96 ppm, 1H each, J=3 Hz, furan ring protons), signals for isopentenyl side chain (5.24 ppm triplet, 7.27 ppm doublet J=6.5 Hz, 8.52 and 8.72 ppm singlets), and two methoxy groups (5.66, 6.96 ppm singlets). Based on these and substituents in 4-methoxyfuranoquinoline alkaloids from H. perforatum seeds (positions 7,8), structure (Ia) or (Ib) was suggested. Treatment with concentrated sulfuric acid yielded a phenolic base isomeric with haplopine; methylation with diazomethane gave skimmianine (identified by comparison with authentic sample), so perfamine has structure (Ia). Continuing separation of the ether-soluble fraction of combined alkaloids from leaves of Liriodendron tulipifera L. (Magnoliaceae) gathered on September 2, 1974 in Tashkent (Botanical Garden of the Academy of Sciences of the Uzbek SSR) on a silica gel column, we isolated (in addition to previously obtained alkaloids) N-methylcrotsparine, lanuginosine, and a new base called liridinine (I), with composition C18H21NO3, mp 142-144°C (acetone), [α]D -38 ° (c 0.095; chloroform), M+ 311. UV spectrum (C2H5OH): λmax 221, 281 nm (log ε 4.41, 4.16). IR spectrum (KBr): 3200-3400 (-OH), 2830, 1290 (-OCH3), 1595, 760 (1,2-disubstituted benzene ring). NMR spectrum (δ scale, CDCl3): singlets at 2.50 (3H, >N-CH3), 3.65 and 3.94 (3H each, 2-OCH3), multiplets at 7.16 (3H, Ar-H), 8.10 ppm (1H, Ar-H). Acetylation with acetic anhydride in pyridine yielded its O-acetate (II) (IR 1760 cm⁻¹). Liridinine is assigned to the aporphine series with one hydroxy group and two methoxy groups. Methylation with diazomethane yielded the O-methyl ether of (I) (III); oxidation of (III) with chromium trioxide in pyridine led to a compound (IV) (mp 162-164°C) identical to liridine (O-methylmoschatoline), so substituting groups are present in ring A at C5, C6 and C7. NMR of O-acetylliridinine (II) shows no carbonyl influence on the C4 aromatic proton (8.14 ppm multiplet), indicating one methoxy group at C5 and the second OCH3/OH group at C6 or C7. Comparing with cassythine, cassythidine, and thalicmine, we consider the most probable position of the second methoxy group in liridinine to be at C7, and propose liridinine as 6-hydroxy-5,7-dimethoxyaporphine (I).

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