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RESEARCH ARTICLE
Year : 2009  |  Volume : 5  |  Issue : 17  |  Page : 67-70 Table of Contents     

Taxane Ditepenoids from the Needles of Taxus baccata L. Growing in Iran


1 Department of Pharmacognosy and Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical sciences, Tehran, Iran
2 Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Date of Submission17-Mar-2008
Date of Decision02-Aug-2008
Date of Acceptance02-Nov-2008
Date of Web Publication30-Dec-2009

Correspondence Address:
Mohammad reza Verdian-Rizi
Department of Pharmacognosy and Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical sciences, Tehran
Iran
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Source of Support: None, Conflict of Interest: None


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   Abstract 

Chemical examination of the needles and young stems of Taxus baccata L. from Iran, resulted in the isolation of three taxane diterpenoids , two previously reported taxoids, taxupinanane L and taxupinanane G, and a new taxoid, 2,9-deacetyltaxinine J. The structures of these compounds were determined on the basis of spectroscopic data. These three taxoids were not previously encountered in Taxus baccata L. species.

Keywords: Taxus baccata L., isolation, taxoids, Taxaceae


How to cite this article:
Verdian-Rizi Mr, Hadjiakhoondi A, Pirali-Hamedani M, Yasa N, Amin G, Khanavi M. Taxane Ditepenoids from the Needles of Taxus baccata L. Growing in Iran. Phcog Mag 2009;5:67-70

How to cite this URL:
Verdian-Rizi Mr, Hadjiakhoondi A, Pirali-Hamedani M, Yasa N, Amin G, Khanavi M. Taxane Ditepenoids from the Needles of Taxus baccata L. Growing in Iran. Phcog Mag [serial online] 2009 [cited 2019 Aug 19];5:67-70. Available from: http://www.phcog.com/text.asp?2009/5/17/67/57988


   Introduction Top


Genus Taxus (Taxaceae) , yew, is widely distributed in the northern hemisphere, and has recently attracted a great deal of attention as sources for an anticancer agent , paclitaxel (Taxol), a unique diterpene taxoid originally extracted from the bark of the pacific yew, Taxus brevifolia [1],[[2],[3] . Paclitaxel has been approved for the treatment of ovarian and breast cancers as well as Kaposi 's sarcoma and non-small-cel lung cancers. It is also under critical trial for treatment of several other cancers in combination with other chemotherapeutic agents [4],[5] .

However, due to the poisonous properties of yew, few records have been encountered as traditional medicine in the literature. Yew leaves are reported to be used in traditional medicine as abortifacient, antimalarial, antiheumatic and for bronchitis [6],[7],[8] , while dried leaves and barks were used against asthma [9] . It was also listed in Avicenna's cardiac drugs [10] .

There are eight Taxus species and two hybrids in the world [11],[12] and Taxus baccata L. (European yew) is the single representative in Iran (13) . Until now, a large number of taxoids possessing different skeleton systems, as well as lignans, flavonoids, steroids and sugar derivatives have been isolated from various Taxus species [2],[3] . During our course of studies on the bioactive components, we have examined constituents of the needles and young stems of Taxus baccata L growing in Iran and isolated three taxoids, taxupinanane L , taxupinanane G, and 2,9­deacetyltaxinine J. In this paper, we would like to describe the isolation and structure elucidation of these natural compounds.

Experimental

General. 1 H and 13C NMR spectrum were recorded in CDCl3 on a Bruker AMX-500 spectrometers with TMS as internal standard. The FAB-MS were obtained on a Keatosl MS9 spectrometer using glycerol as F 254 matrix. Column chromatography (CC) was performed by using silica gel (Kieselgel 60, 0.63-0.200 mm, Art. 7734, Merck) and Kieselgel 60 F254 (0.5 mm thickness, Art. 5554, Merck) was used for preparative thin layer chromatography (PTLC). Analytical TLC was performed on precoated plates (Kieselgel 60 F254, Art. 5554, Merck) and visualized under UV254 light, and then sprayed with anisaldehyde reagent and heated.

Plant material. The needles and young stems of Taxus baccata L. was collected from Sari, north of Iran, in November 2006. A voucher specimen has been located at the Herbarium of Faculty of Pharmacy, Tehran University of Medical Sciences.

Extraction and Isolation.

The air-dried and powdered needles and young stems (3 Kg) were extracted three times with methanol (MeOH) at room temperature. The methanolic extract was evaporated to dryness in vacuo and a reddish residue was obtained. The residue was diluted with distilled water and extracted three times with hexane to remove the major part of the neutral and lipid materials which were not investigated further. The resulting residue was extracted three times with CH 2 Cl 2 and the combined CH 2 Cl 2 extracts were evaporated under reduced pressure to give a residue (50g). This residue was subjected on column chromatography (CC) eluted with hexane-ethyl acetate (2:1, 1:1, 1:2, 1:4). Twelve fractions were obtained and each was evaporated to dryness under reduced pressure. Fractions 5 (900mg), 6 (750mg) and 7 (450mg) were further separated by preparative thin layer chromatography (PTLC) repeatedly with different developing solvents (CHCl 3 -Me0H, hexane-EtoAc, hexane-acetone) and finally compound 1 (3mg), 2 (12mg) and 3 (4.8 mg) were obtained in pure form.


   Results and Discussion Top


A methanolic extract of the needles and young stems of Taxus baccata L. was processed as described in the Experimental Section to provide three taxane diterpenoids.

Compound 1 was isolated as a colorless amorphous solid in a 0.0001 % yield based on the dry material. A molecular formula of C 35 H 44 0 9 was established on the basis of 13 C NMR and FAB-MS spectrum. Analysis of the 1 H and 13 C NMR spectrum data suggested the presence of a 6/8/6-membered ring system while 1 H and 13C NMR data of 1 resembled those of taxinine E. The 13C NMR spectrum showed signals due to five oxygenated carbons, one tetrasubstituted olefin, one monosubstituted aromatic ring, seven methyl groups, one keto carbonyl group and three ester carbonyl groups. Three acetyl groups were observed at δH 1.77, 2.06 and 2.09 (each 3H, s), this being confirmed by the respective signals at δc 21.03 (q), 21.03 (q), 20.80 (q), and by the corresponding carbonyl carbons at δc 170.28 (s), 169.84 (s) and 170.70 (5). The olefin protons signals of a cinnamoyl group at C-5 appeared at δH 7.78 (1H, d ,J=16.0 Hz), 6.66 (1H, d, J=16.0 Hz) and 7.41­7.45 (5H, m) and a OH group attached at C-2, δH 1.53 (1H, brs). The presence of 4(20)-unsaturation in 1, common in non-oxetane type taxoids (6), was also apparent from the 1 H and 13 C NMR spectrum data, δH at 5.57 (s) and 5.51 (5), δc at 119.40 (t) and 143.44 (5). As the 1 H and 13 C NMR spectrum data of the compound 1 was similar to those of taxupinanane L, the structure of compound 1 was assigned to be taxupinanane L.

Compound 2 was isolated as a colorless gummy substance in a yield of 0.0004 % based on the dry material. The 13 C NMR and FAB-MS spectrum revealed the molecular formula to be C 37 H 46 0 11 . The 13 C NMR spectrum showed signals due to six oxygenated carbons, one tetrasubstituted olefin, one monosubstituted aromatic ring, eight methyl groups, one keto carbonyl group and four ester carbonyl groups. The 1 H and 13 C NMR spectrum had well-dispersed signals suggestive of a taxane derivative with a 6/8/6-membered ring system containing four acetate groups at δH 1.98, 2.03, 2.09 and 2.11 (each 3H,s), this being confirmed by the respective signals at δc 2.99(s), 21.3(s), 21.3(s) and 21.33(s), and by the corresponding carbonyl carbons at δc 170.00(s), 171.00(s), 170.00(s) and 171.00(s). In addition, The 1H and 13 C NMR spectrum revealed signals due to one cinnamoyl group at δH 7.78 (1H, d, J=16.0 Hz), 6.66 (1H,d, J=16.0 Hz) and 7.40-7.49 (SH,m). Since the 1H and 13 C NMR signals were very close to those of taxupinanane G, the structure of 2 was assigned to be taxupinanane G.

Compound 3 was isolated as a white amorphous solid in a 0.00016 % yield based on the dry material. By the combined analysis of FAB-MS, 1 H NMR and 13 C NMR spectrum data, the molecular formula was proposed as C35H44010. The 1 H NMR spectrum showed the four tertiary methyl groups at δH 0.98, 1.71, 1.19 and 2.26 (each 3H, s) assignable to the 8-CH 3 , 15-(CH 3 )2 and 12- CH 3 groups, respectively. Three acetyl groups at δH 2.10, 2.16 and 2.18 (each 3H, s) at relatively low field, six oxy-bearing methane groups at 6 H 5.87 (d, J=10 Hz), 5.45 (d, J=10.4 Hz), 5.32 (m), 4.30 (d, J=9.6) and 4.13 (d, J=6.8 Hz), one tow substituted olefin at δH 5.38 (s) and 5.47 (s) were also involved. One tetra substituted olefin at δc 138.00 (s) and 136.00 (5), was deducted from the 13 C NMR spectrum. The 1 H NMR spectrum also suggested one cinnamoyl group at δH 7.65 (1H, d, J=16.0 Hz), 6.39 (1H, d, J=16 Hz), 7.42 (3H, m) and 7.45 (2H, m) and two OH groups attached at C-2 at δH 1.56 (brs) and C-9 at δH 2.05 (d, J=3.8 Hz). The 1 H NMR and 13 C NMR spectrum data closely resembled to those of taxupinanane G, with the exemption of one signal upfielded to δH 4.30 in 1 H NMR spectrum and an acetyl group disappeared both in 1H NMR and 13 C NMR spectrum. We compared the chemical shifts of H 9 and H 10 in several previously known structures of derivatives of taxinine such as [Additional file 1] taxinine J, taxezopidine H, danataxusin B and so on to determine the structure of 3. In addition, a dd­coupling for H 9 was observed in 3 that is related to the coupling of the hydroxyl group at δH 2.05 as dd with J=3.8 Hz, which could support the structure of 3 . Finally we concluded that the structure of 3 should be 2,9-deacetyltaxinine J.[Table 1]

 
   References Top

1.M.C. Wain. H.L. Taylor, M.E. Wall, P. Coggon and A.T. McPhail, Plant antitumor agents. VI. The isolation and structure of taxol, a novel anti leukemic and antitumor agent from Taxus brevifolia. Journal of American Chemical Society 93 (1971), pp. 2325-2327  Back to cited text no. 1      
2.E. Baloglu and D.G.I. Kingston, The taxane ditcrpcnoids. Journal of Natural Products 62 (1999), pp. 1448-1472  Back to cited text no. 2      
3.V.S. Parmar. A. Jha, K.S. Bisht, P. Taneja, S.K. Singh, A. Kumar. P. Raijni Jain and C.E. Olsen, Constituents of yew trees. Phvtochemistry 50 (1999). pp. 1267-1304  Back to cited text no. 3      
4.E.K. Rowinsky. The development and clinical utility of the Taxane class of antimicrotuhule chemotherapy agents. Annual Review of Medicine 48 (1997), pp. 353- 374E.A.  Back to cited text no. 4      
5.Eiscnhauer and J.B. Vermorken, The taxoids. Drugs 55 (I 998). pp. 5-30  Back to cited text no. 5      
6.T. Bryan-Brown, The pharmacological actions of taxine. Quaterly Journal of Pharmacy and Pharmacology 5 (1932). pp. 205-219.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]  
7.G. Appcndino, Taxol (paclitaxel): historical and ecological aspects. Fitoterapia 64 (1993), pp. 5-25  Back to cited text no. 7      
8.M. Ballero and I. Fresu. Le piante di use officinale nclla Barbagia di Seui (Sardegna Centrale). Fitoterapia 64 (1993), pp. 76-83.  Back to cited text no. 8      
9.V. Singh, Traditional remedies to treat asthma in North West and Trans-Himalayan region in J&K State. Fitoterapia 66 (1995), pp. 507-509  Back to cited text no. 9      
10.Tekol, Ibn Sina's cardiac drug Zarnab. Hamdard 32 (1989). pp. 73-77  Back to cited text no. 10      
11.E.L.M. Van Rozendall, S.J.L. Kurstjens, T.A. Van Beek and R.G. Van Den Berg, Chemotaxonomy of Taxus. Phytochemistry 52 ( I 999), pp. 427-433.  Back to cited text no. 11      
12.Davis, P.H., Cullen. J., 1965. Taxus L. In: Davis, P.H. (Ed.), Flora of Turkey and the East Aegean Islands, vol. . University Press, Edinburgh, p. 565  Back to cited text no. 12      



 
 
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