Terpenoids and Flavones from Achillea falcata (Asteraceae)
Maurizio Bruno,1 Sergio Rosselli,1 Rosa Angela Raccuglia,1 Antonella Maggio,1 Felice Senatore,2 Nelly Apostolides Arnold,3 Claire A. Griffin4 and Werner Herz4
1 Dipartimento di Chimica Organica, Universitá di Palermo, Viale de Scienze, Pardo d'Orleans II, 90128 Palermo, Italy.
2 Dipartimento Chimica Sostanze Naturali, Universitá Federico II, via D. Montesano, 49-80131 Napoli, Italy.
3 Faculté des Sciences Agronomiques, Université Saint Esprit, Kaslik (Beirut), Lebanon.
4 Department of Chemistry and Biochemistry, The Florida State University, Tallahassee, FL 32306-4390, USA. Tel: (1)-850-644-2774; Fax: (1)-850-644-8281. E-mail: jdulin@chem.fsu.edu
]]>Recibido el 25 de febrero del 2003.
Aceptado el 2 de abril del 2003.
Dedicated to Professor Alfonso Romo de Vivar, a valued collaborator during the early stages of his career.
Abstract
Aerial parts of Achillea falcata L. furnished the monoterpenes 3,7-dihydroxy-3,7-dimethyl-1,5-octadiene and 3,6-dihydroxy-3,7-dimethyl-1,7-octadiene, the sesquiterpene lactone sintenin and the flavonoids 5-hydroxy-6,7,3', 4'-tetramethoxyflavone (6-hydroxy-luteolin-6,7,3',4'-tetramethyl ether) and 5-hydroxy-6,7,8,3',4'-pentamethoxyflavone (desmethoxynobiletin).
Keywords: Achillea falcata, Asteraceae, monoterpenes, sesquiterpene lactone, sintenin, flavonoids.
]]> Resumen
El análisis químico de las partes aéreas de Achillea falcata permitió la caracterización de los monoterpenos 3,7-dihidroxi-3,7-dimetil-1,5-octadieno y 3,6-dihidroxi-3,7-dimetil-1,7-octadieno, la lactona sesquiterpénica sintenina y los flavonoides 5-hidroxi-6,7,3',4'-tetrametoxi-flavona (6,7,3',4'-tetrametil éter de 6-hidroxi-luteolina) y 5-hidroxi-6,7,8,3',4'-pentametoxiflavona (desmetoxinobiletina).
Palabras clave: Achillea falcata, asteraceae, monoterpenos, lactona sesquiterpénica, sintenina, flavonas.
Our groups have previously described the chemistry of two Achillea species, A. ligustica All. from Sicily [1] and A. cretica L. from Cyprus [2]. We now report the results of our study of Achillea falcata L. from Lebanon.
Aerial parts of A. falcata L. (syns. A. damascene DC, A. sulfurea Boiss.) were extracted at room temperature with acetone; the extract was purified by silica gel chromatography and radial chromatography to afford five compounds. Of these, 5-hydroxy-6,7,3',4'-tetramethoxyflavone(6-hydroxyluteolin-6,7,3',4'-tetramethyl ether) and 5-hydroxy-6,7,8,3'4'-pentamethoxyflavone (desmethoxynobiletin) were identified by MS and comparison of their 1H-NMR spectra with spectra in our files. Two others, the monoterpenes 3,7-dihydroxy-3,7-dimethyl-1,5-octadiene (1) and its isomer 3,6-dihydroxy-3,7-dimethyl-1,7-octadiene (2), have been previously reported from Cinnamum camphora [3]; diene 1 has also been isolated in our laboratories from Achillea ligustica All. [1] where its high resolution 1H NMR spectrum was reported. Doubling of the signals of H-1a, H-1b and H-2 in our 500 MHz 1H NMR spectrum of 2 (see Experimental section) indicated that it was a 1:1 mixture of C-3 epimers. The remaining constituent was the germacradienolide sintenin (3) first reported with incorrect C-9 stereochemistry from Achillea sintenisii Hub.-Mor. [4], a matter subsequently corrected with material from Achillea biebersteinii Afran (as A. micrantha Willd.) [5].
Sintenin has also been isolated from the near Eastern species A. aleppica DC. and pseudoaleppica Hub. Mor. [6], A. cucullata (Hausskn.) Bornm., A. goniocephala Boiss. et Bal. and A. vermicularis Trin. [7] as well as from A. teretifolia Willd. [8], all, like A. sintenisii, A. biebersteinii and now A. falcata, members of Achillea sect. Santolinoidea C. Koch [9] which suggests that sintenin might be a marker for the section. An exception is the Balkan species A. crithmifolia Waldst. et Kit. several collections of which [10-13] yielded a variety of sesquiterpene lactone types among which sintenin appeared only once [12].
Experimental section
]]> General experimental procedures. Column chromatography was performed using Merck Si gel (No. 7734). 1H NMR spectra were obtained on a Varian Inova 500 MHz NMR spectrometer in CDCl3, whereas 13C NMR spectra were run on an IBM/Bruker WP27OSY NMR spectrometer at 67.5 MHz in CDCl3. Mass spectra were acquired on a JEOL MS Route 600 H instrument.Plant material. Aerial parts of Achillea falcata L. were collected at Jab. Kneissé, Lebanon at 1700 m s / l in July 2000. A voucher specimen (leg., det. and confirmed by N. Arnold s.n. is deposited in the herbarium of the Botanical Garden and the Botanische Museum, Freie Universität Berlin, Germany.
Extraction and isolation. Dried and powdered aerial parts (750 g) were extracted with acetone (3 × 5 l) at room temperature for one week each time. The extracts were combined and evaporated at reduced pressure and low temperature (35 °C) to give 58 g of residue. The residue was subjected to dry column chromatography over Si gel with a solvent gradient ranging from petroleum ether (bp 50-70 °C) to EtOAc (100 %) and finally with EtOAc-MeOH (19:1 and 9:1). The fraction eluted with petroleum ether-EtOAc (2:3) was resubmitted to chromatography using petroleum ether-EtOAc (4:1, 3:7 and 1:1) as eluent to afford several subfractions. The subfraction eluted with petroleum ether-EtOAc (3:70 weighing 250 mg was subjected to radial chromatography using CH2Cl2-MeOH (99:1) as eluent to afford, in order of increasing polarity, desmethokynobiletin (20 mg) identified by MS and 1H NMR spectrometry, sintenin (10 mg), identified by MS, 1H and 13C NMR spectrometry [5], and 10 mg of 2. The subfraction eluted with petroleum ether-ethyl acetate (1:1) weighing 200 mg was subjected to radial chromatography using CH2Cl2-MeOH (49:1) as eluent to afford in order of increasing polarity 60 mg of 5-hydroxy-6,7,3',4'-tetramethoxyflavone and 45 mg of 1.
3,7-Dihydroxy-3,7-dimethyl-1,5-octadiene (1): Mass and 1H NMR spectra corresponded to data reported earlier. 3,6-Dihydroxy-3,7-dimethyl-1,7-octadiene (2): 1:1 mixture of C-3 epimers; oil, MS CI (isobutene) 153.1279 (25), 135.1174 (21.9); calcd for C10H18-O2H2O + H 153.1279; for C10H18O2- 2H2O + H, 135.1174; 1H NMR (CDCl3) δ 5.89 and 5.88 (both dd, J = 17.3, 10.8 Hz, H-2 of epimers A and B), 5.22 and 5.21 (both dd, J = 17.3, 1.4 Hz, H-1a of epimers A and B), 4.94 and 4.93 (both q, J = 4, 1 Hz, H-8a of both epimers), 4.83 and 4.82 (both q, 4 Hz, H-8b of both epimers), 4.04 (brq, 6.3 Hz, H-6 of both epimers, 1.70 (brs, 3H, H-8), 1.64-1.53 (c, 4H, H-4a,b H-5a,b), 1.28 s (3H, H-10).
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