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ORIGINAL ARTICLE
Year : 2010  |  Volume : 2  |  Issue : 3  |  Page : 159-162 Table of Contents     

Triterpenes from Euphorbia rigida


1 Laboratory of Natural Products and Organic Synthesis, Department of Chemistry, Faculty of Science, University Mentouri - Constantine, Algeria
2 Department of Chemistry, Aswan-Faculty of Science, South Valley University, Aswan, Egypt
3 Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmacy, Applied Sciences University, Amman, Jordan - 119 31, Jordan
4 Department of Pharmacognosy, Faculty of Pharmacy, El-Minia University, El-Minia - 615 19, Egypt
5 Chemistry of Medicinal Plant Department, National Research Centre, Dokki, Giza - 126 22, Egypt
6 Department of Biological Sciences, College of Science, King Khalid University, 61413, Saudi Arabia
7 Department of Botany, Aswan-Faculty of Science, South Valley University, Aswan, Egypt

Date of Submission20-Feb-2010
Date of Decision05-Jun-2010
Date of Web Publication19-Jul-2010

Correspondence Address:
Magdi A El-Sayed
Department of Botany, Aswan-Faculty of Science, South Valley University, Aswan
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0974-8490.65510

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   Abstract 

Phytochemical studies of the aerial parts of Euphorbia rigida afforded three triterpenes: betulin (1), cycloart-23Z-ene-3, 25-diol (2) and cycloartan-3, 24, 25-triol (3), firstly isolated from this plant. The structures and relative stereochemistry were determined on the basis of extensive spectroscopic analyses, including 1D and 2D NMR experiments (1H NMR, 13C NMR, COSY, NOESY, HMQC and HMBC).

Keywords: Euphorbia rigida, Euphorbiaceae, cycloartan triterpene


How to cite this article:
Gherraf N, Zellagui A, Mohamed NS, Hussien TA, Mohamed TA, Hegazy MEF, Rhouati S, Moustafa MF, El-Sayed MA, Mohamed AHH. Triterpenes from Euphorbia rigida. Phcog Res 2010;2:159-62

How to cite this URL:
Gherraf N, Zellagui A, Mohamed NS, Hussien TA, Mohamed TA, Hegazy MEF, Rhouati S, Moustafa MF, El-Sayed MA, Mohamed AHH. Triterpenes from Euphorbia rigida. Phcog Res [serial online] 2010 [cited 2019 May 26];2:159-62. Available from: http://www.phcogres.com/text.asp?2010/2/3/159/65510


   Introduction Top


Euphorbia genus belongs to the family Euphorbiaceae. This family comprises about 300 genus and 5000 species distributed mainly in America and tropical Africa. [1] Euphorbia species have been used in folk medicine to treat skin diseases, migraines, intestinal parasites and warts. [2] The biological activities of the genus, including antitumor, antiviral, cytotoxic properties and different vascular effects, are generally attributed to the presence of specific types of diterpenes, both macrocyclic and polycyclic derivatives. [3],[4],[5] The skin irritant and tumor-promoting properties of tigliane, ingenane and dephanane diterpenes of this plant are well known. Considerable attention has recently been given to the macrocyclic diterpenes because of their high chemical diversity and therapeutically relevant bioactivity. [6],[7],[8] Jatrophane and modified jatrophane diterpenoids, which are rare in the genus Euphorbia, are potent inhibitors of a membrane protein (so-called P-glycoprotein) pumping cytotoxic drugs out of cells and conferring upon the cells the ability to resist high doses of these drugs. [9] Therefore, the genus has been subjected to numerous chemical studies and these have led to the isolation of diterpenes [10],[11] dimeric diterpenoid [12] diterpene polyesters [11],[13] triterpenes [14] and pentacyclic triterpenes. [15] Few sesquiterpenoids and flavonoids have been isolated from the genus. [16],[17]

Spurges Epuhorbia species are a common constituent of many ancient treatments of mouse leukemia and diseases such as cancer, swelling and warts. [18]


   Materials and Methods Top


Plant material

The aerial parts of Euphorbia rigida were collected from Greek in August 2004, by Dr. Olga Tzakou, Department of pharmacy and Chemistry of Natural products, Faculty of Pharmacy, University of Athens, Greece.

Extraction and isolation

The air-dried plant (1 kg) was crushed and extracted with CH 2 Cl 2 -MeOH (1:1) at room temperature. The extract was concentrated in vacuo to obtain a residue (30 g). The residue was fractionated by silica gel CC (6 Χ 120 cm) eluted with n-hexane (3 l), followed by a gradient of n-hexane-CH 2 Cl 2 up to 100% CH 2 Cl 2 and CH 2 Cl 2 -MeOH up to 15% MeOH (2 l of each solvent mixture) with increasing degree of polarity. The n-hexane-CH 2 Cl 2 (1:1) was pre-fractionated by CC using Sephadex LH-20 (2 Χ 40 cm) and eluted with n-hexane-CH 2 Cl 2 (7:4) to give compound 1 (80 mg). Compound 2 (60 mg) was isolated from n-hexane-CH 2 Cl 2 (2:3) fraction and the latex was pre-fractionated by CC on Sephadex LH-20 (1 Χ 30 cm) and eluted with n-hexane-CH 2 Cl 2 -MeOH (7:4:0.25). Compound 3 (30 mg) isolated from 100% CH 2 Cl 2 fraction, was pre-fractionated by CC on Sephadex LH-20 (1 Χ 30 cm) and eluted with n-hexane-CH 2 Cl 2 -MeOH (7:4:0.5).


   Results and Discussion Top


Repetitive chromatographic steps of the methylenechloride/methanol (1:1) extract of the air-dried aerial parts of E. rigida yielded three known triterpenes [Figure 1].

Compound 1 was obtained as a white powder. The structure of 1 was determined from careful investigation of the 1D and 2D NMR measurements. The 1 H-NMR spectrum (600 MHz, CDCl 3) [Table 1] showed the triterpenoid pattern with six methyl singlets in the up-field at δH 0.74 (Me-24), 0.79 (Me-25), 0.92 (Me-23), 0.94 (Me-27), 0.99 (Me-26) and the one methyl group of Me-30 appeared as a sharp singlet at δH 1.68 (Me-30). The down-field shift for Me-30 indicated the presence of a double bond between C-20 and C-29. In the down-field of spectrum, there were two broad singlets: at δH 4.65 (1H, br s, H-29 a) and 4.55 (1H, br s, H-29 b), suggesting the presence of an olefinic proton. The HMQC spectrum showed correlations between H-29 a at δH 4.65 (1H, br s) and H-29 b at δH 4.55 (1H, br s) with carbon signal at δC 109.72. Additionally, the hydroxylated methylene protons at δH 3.75 (1H, d, J = 9 Hz, H-28 a), coupled in 1 H- 1H COSY spectrum with a signal at δH 3.32 (1H, d, J = 9 Hz, H-28 b), giving a doublet. The HMQC spectrum showed correlation between H28 a at δH 3.75 (1H, d, J = 9 Hz) and H-28 b at δH 3.32 (1H, d, J = 9 Hz) with carbon at δC 60.39. The 1 H NMR also revealed a secondary hydroxyl group placed at C-3, inferred from the down-field shift of methine proton which appeared at δH 3.18 (1H, dd, J = 8, 3.2 Hz, H-3) which showed correlation in HMQC with carbon signal at δC 78.86.

The 13 C-NMR spectrum (125 MHz, CDCl 3) [Table 2] displayed 30 carbon signals and DEPT experiments indicated these signals corresponding to 6 methyl groups, 12 methylene groups, including one attached to oxygen appearing at δC 60.42 for C-28. Six methine groups including one attached to oxygen appeared at δC 78.86 for C-3 and six quaternary carbon atoms. The olefinic carbons C-20 and C-29 appeared at δC 15.46 and 109.77, respectively. HMQC and HMBC were used to determine the position of the hydroxylated methyl carbons; the two proton signals at δH 3.75 (H-28 a) and 3.32 (H-28 b) seen in the HMBC experiment show clear long-range correlations between the carbon signals at δC 29.15 (C-16), 33.95 (C-22) and 47.74 (C-17), while the carbon signal at δC 60.39 (C-28) showed a correlation with the proton signal at δH 1.03 (H-22 a), 1.85 (H-22 b), 1.28 (H-16 a). Other important correlations were observed between the carbon signals at δC 15.35 (C-24), 27.96 (C-23) and 38.64 (C-1) with the proton signal at δH 3.18 (H-3). Therefore, the hydroxylated methyl was placed at C-3. The assignment of all proton signals and their connectivity to adjacent protons and carbon signals were established from the results of 2D 1 H- 1 H COSY and HMQC experiments.

Acetylating of 1 gave the diacetyl derivative ( 1a), for which the 1 H NMR spectrum displayed two new acetyl signals and confirmed the structure of compound 1 . The structure of compound 1 was deduced from the comparison of its spectral data with those of literature and identified as betulin. [19],[20]

Compound 2 was isolated as colorless needles. The 1 H-NMR spectrum (600 MHz, CDCl 3) [Table 1] of compound 2 displayed two doublets at δH 0.22 (1H, d, J = 4.5 Hz, H-19a) and at 0.01 (1H, d, J = 4.5 Hz, H-19b) which are characteristic of the presence of a C-9/C-10 cyclopropyl methylene group of a cycloartan-3-one triterpenoid. Cycloartane-type triterpenes possess a cyclopropane bridge between C-9 and C-10, and protons attached to cyclopropyl rings characteristically appear as a pair of doublets in the high-field 1 H-NMR region with gem-coupling constant (J = 4.5 Hz). The 1H-NMR spectrum showed the presence of an olefinic proton double bond at δH 5.26 (2H, d, J = 8, H-23, H-24). The low coupling constant (J = 8 Hz) between H-23 and H-24 indicate the stereochemistry "Z" at C-23. The HMQC spectrum showed correlation between H-23 at δH 5.26 (1H, d, J = 8) with carbon signal at δC 139.31 and H-24 at δH 5.26 (1H, d, J = 8) with carbon signal at δC 125.57. Additionally, δH 2.95 (1H, m, H-3) which suggested the existence of secondary hydroxyl group. The 1 H-NMR spectrum showed the presence of six tertiary methyl groups as a singlet at δH 0.42 (3H, s, Me-29), 0.56 (3H, s, Me-30), a sharp signal that integrated for six protons at δH 0.62 (6H, s, Me-18, Me-28), 0.98 (6H, s, Me-26, Me-27) and one methyl group at δH 0.53 (3H, d, J = 6.5 Hz, Me-21) coupled with H-20 (methine proton) gave a doublet.

The 13 C-NMR spectrum (125 MHz, CDCl 3) [Table 2] of compound 2 showed the presence of 30 carbon signals. Determination of the multiplicity was carried out by DEPT experiments which indicated the presence of 6 quaternary carbon atoms, 7 methine groups, 10 methylene groups and 7 methyl groups. It also showed the presence of two olefinic carbons C-23 and C-24 appearing at δC 139.31 and 125.57, respectively. Two oxygenated carbons appeared at δC 78.80 for C-3 and at 70.75 for C-25. The structure of compound 2 was deduced from the comparison of its spectral data with those of literature and identified as cycloart-23 Z-ene-3, 25-diol. [21],[22]

Compound 3 was isolated as colorless needles. The 1 H-NMR spectrum (500 MHz, CDCl 3) [Table 1] of compound 3 displayed two doublets at δH 0.55 (1H, d, J = 4.5 Hz, H-19 a) and at 0.3 (1H, d, J = 4.5 Hz, H-19 b) which are characteristic of a C-9/C-10 cyclopropyl methylene group of a cycloartan-3-one triterpenoid. Cycloartane-type triterpenes possess a cyclopropane bridge between C-9 and C-10, and protons attached to cyclopropyl rings characteristically appear as a pair of doublets in the high-field 1 H-NMR region with a gem-coupling constant (J = 4.5 Hz). Additionally, the presence of triplet bonds at δH 3.35 (1H, t, J = 3.2 Hz, H-3) and multiplet bands at δH 3.25 (1H, m, H-24) suggested the existence of secondary hydroxyl group. The 1 H-NMR spectrum showed the presence of six tertiary methyl groups at δH 0.75 (3H, s, Me-29), 0.88 (3H, s, Me-30), a sharp signal appearing at δH 0.97 (6H, s, Me-18, Me-28), 1.12 (3H, s, Me-26), 1.24 (3H, s, Me-27) and one methyl group at δH 0.87 (3H, d, J = 3.2 Hz, Me-21) coupled with H-20 (methine proton) gave a doublet.

The 13 C-NMR spectrum (125 MHz, CDCl 3) [Table 1] of compound 3 showed the presence of 30 carbon signals. Determination of the multiplicity was carried out by DEPT experiments which revealed the presence of 7 methyl groups, 11 methylene groups, 6 methine groups with two oxygenated carbons at δC 78.83 for (C-3), 79.63 for (C-24) and 6 quaternary carbon signals with 1 oxygenated at δC 76.74 for (C-25).

The structure of compound 3 was deduced from the comparison of its spectral data with those of literature and was identified as cycloartan-3, 24, 25-triol. [23],[24],[25],[26]


   Acknowledgment Top


The authors thank Dr. Olga Tzakou for providing the plant species.

 
   References Top

1.Webester G. Systematic of the Euphorbiaceae: Introduction. Ann Miss Bot Gard 1994;81:133-44.  Back to cited text no. 1      
2.Singla A, Pathak K. Phytoconstituents of Euphorbia species. Fitoterapia 1990;61:483-516.  Back to cited text no. 2      
3.Appendino G, Spagliardi P, Ballero M, Seu G. Macrocyclic diterpenes from Euphorbia hyberna L. subsp. Insularis and their reaction with oxyphilic reagents. Fitoterapia 2002;73:576-82.  Back to cited text no. 3      
4.Haba H, Lavaud C, Harkat H, Alabdul Magid A, Marcourt L, Benkhaled M. Diterpenoids and triterpenoids from Euphorbia guyoniana. Phytochemistry 2007;68:1255-60.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]  
5.Hohmann J, Evanics F, Dombi G, Szabo P. Salicifoline and Salicinolide, new diterpene polyesters from Euphorbia salicifolia. Tetrahedron Lett 2001;42:6581-4.  Back to cited text no. 5      
6.Evans FJ, Taylor SE. Proinflammatory tumor-promoting and anti-tumor diterpenes of the plant families Euphorbiaceae and Thymillaeaceae. In: Herz W, Grisebach H, Kirby GW, editors. Progress in the Chemistry of Organic Natural Products.Springer-Verlag, New York, 1983, pp. 1-99.  Back to cited text no. 6      
7.Sahai R, Rastogi RP, Jakupovic J, Bohlmann F. A diterpene from Euphorbia maddeni. Phytochemistry 1981;20:1665-7.   Back to cited text no. 7      
8.Uemura D, Katayama C, Uno E. Kansuinine B. A novel multi oxygenated diterpene from Euphorbia kansui Liou. Tetraherdron Lett 1975;21:1703-6.  Back to cited text no. 8      
9.Corea G, Fattorusso E, Lanzotti V, Taglialatela-Scafati O, Appendino G, Ballero M, et al. Jatrophane diterpenes as P-glycoprotein inhibitors. First insights of structure-activity relationships and discovery of a new, powerful lead. J Med Chem 2003;46:3395-402.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]  
10.Abdelgaleil SA, Kassem SM, Doe M, Baba M, Nakatani M. Diterpenoids from Euphorbia paralias. Phytochemistry 2001;58:1135-9.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]  
11.Hohmann J, Evanics F, Dombi G, Molnar J, Szabo P. Euphosalicin, a new diterpene polyester with multidrug resistance reversing activity from Euphorbia salicifolia. Tetrahedron 2001;57:211-5.  Back to cited text no. 11      
12.Zhou TX, Bao GH, Ma QG, Qin GW, Che CT, Liv Y, Wang C, Zheng QT. Langduin C. A novel dimeric diterpenoid from the roots of Euphorbia fischeriana. Tetraherdron Lett 2003;44:135-7.  Back to cited text no. 12      
13.Hohmann J, Redei D, Evanics F, Kalman A, Argay G, Bartok T. Serrulatin A and B. New Diterpene Polyesters from Euphorbia serrulata. Tetraherdron 2000;56:3619 -23.  Back to cited text no. 13      
14.Ilyas M, Parveen M, Amin KM. Neriifolione. A triterpene from Euphorbia neriifolia. Phytochemistry 1998;48:561-3.  Back to cited text no. 14      
15.Lima EM, Medeiros JM, Davin LB. Pentacyclic triterpenes from Euphorbia stygiana. Phytochemistry 2003;63:421-5.  Back to cited text no. 15  [PUBMED]  [FULLTEXT]  
16.Shi JG, Shi YP, Jia, ZJ. Sesquiterpenoids from Euphorbia wangii. Phytochemistry 1997;45:343-7.  Back to cited text no. 16      
17.Rizk AM, Youssef AM, Diab MA, Salem HM. Constituents of Egyptian Euphorbiaceae. Part 2: Flavonoids of Euphorbia segetalis Pharmazie 1976;31:405-7.  Back to cited text no. 17      
18.Fatope MO, Zeng L, Ohayaga JE, Shi G, McLaughlin JL. Selectively cytotoxic diterpenes from Euphorbia poisonii. J Med Chem 1996;39:1005-8.  Back to cited text no. 18  [PUBMED]  [FULLTEXT]  
19.Margret MO, Michel DB, Christopher SC, Barbara JWC. Betulin and lupeol in bark from four white-barked birches. Phytochemistry 1988;27:2175-6.  Back to cited text no. 19      
20.Tinto WF, Blair LC, Alli A, Reynolds WF, Mclean S. Lupane triterpenoids of Salacia cordata. J Nat Prod 1992;55:395-8.  Back to cited text no. 20      
21.Khan MT, Khan SB, Ather A. Tyrosinase inhibitory cycloartane type triterpenoids from the methanol extract of the whole plant of Amberboa ramosa Jafri and their structure-activity relationship. Bioorg Med Chem 2006;14:938-43.  Back to cited text no. 21  [PUBMED]  [FULLTEXT]  
22.Garcez FR, Nunez CV, Garcez WS, Almeida RM, Roque NF. Sesquiterpenes, limonoid and coumarin from the wood bark of Guarea guidonia. Planta Med 1998;64:7-80.  Back to cited text no. 22      
23.Akira I, shintaro O, Takako S, Hiroko M, Yuka I, Dedy D, Tsutomu N. Cycloartane triterpenoids from Aglaia harmsiana. Phytochemistry 1997;46:379-81.  Back to cited text no. 23      
24.Hisham A, Bai A, JayaKumar G, Nair MS, Fujimoto Y. Triterpenoids from Dysoxylum malabaricum. Phytochemistry 2001;56:331-4.  Back to cited text no. 24  [PUBMED]  [FULLTEXT]  
25.Nyemba AM, Mpondo TN, Connolly JD, Rycroft DS. Cycloartane derivatives from Garcinia lucida. Phytochemistry 1990;29:994-7.  Back to cited text no. 25      
26.Satti NK, Suri OP, Dhar KL, Atal CK, Kawasaki T, Miyahara K, Kawano S. High resolution NMR and x-ray crystallography data of caudicifolin from Euphorbia acaulis. Phytochemistry 1986;25:1411-3.  Back to cited text no. 26      


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2]


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