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A furan-2-carbonyl C-glucoside and an alkyl glucoside from the parasitic plant, Dendrophthoe pentandra
Phytochemistry Letters 21 (2017) 90–93
Contents lists available at ScienceDirect
Phytochemistry Letters journal homepage: www.elsevier.com/locate/phytol
Short communication
A furan-2-carbonyl C-glucoside and an alkyl glucoside from the parasitic plant, Dendrophthoe pentandra
MARK
Poolsak Sahakitpichana, Wannaporn Disadeea, Rada Buntawonga, Nitirat Chimnoia, ⁎ Somsak Ruchirawata, Tripetch Kanchanapooma,b, a b
Chulabhorn Research Institute, Kamphaeng Phet 6, Talat Bang Khen, Lak Si, Bangkok 10210, Thailand Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
A R T I C L E I N F O
A B S T R A C T
Keywords: Dendrophthoe pentandra Loranthaceae Furan-2-carbonyl C-glucoside scleropentaside F Alkyl glucoside
A new furan-2-carbonyl C-(6′-O-galloyl)-β-glucopyranoside (scleropentaside F, 1) and a new alkyl glucoside [butane-2,3-diol 2-(6′-O-galloyl)-O-β-glucopyranoside, 2] were isolated from the entire hemi-parasitic plant, Dendrophthoe pentandra growing on Tectona grandis together with ten known compounds including, benzyl-O-βD-glucopyranoside (3), benzyl-O-α-L-rhamnopyranosyl-(1 → 6)-β-D-glucopyranoside (4), benzyl-O-β-D-apiofuranosyl-(1 → 6)-β-D-glucopyranoside (5), methyl gallate 3-O-β-D-glucopyranoside (6), methyl gallate 3-O-(6′-Ogalloyl)-β-D-glucopyranoside (7), (+)-catechin (8), procyanidin B-1 (9) and procyanidin B-3 (10), bridelionoside A (11), and kiwiionoside (12). In addition, compounds 1, 3–9 were isolated from this species growing on the different host, Mangifera indica. The structure elucidations were based on physical data and spectroscopic evidence including 1D and 2D experiments.
1. Introduction Dendrophthoe pentandra (L.) Miq. (Thai name: Ka-Fak-Ma-Muang, Family Loranthaceae) is a hemi-parasitic plant, generally grown on a variety of host plants. It is used in Thai traditional medicine for treating hypertension and diabetes. Previous phytochemical investigation of this plant growing on Annona squamosa L. (Family Annonaceae) and Artocarpus heterophyllus Lam. (Syn. A. integrifolius L, f., Family Moraceae) reported the isolation of flavonoids, steroids and triterpenoid (Nguyen et al., 2010, 2011). In the biological properties, the antioxidant, anti-diabetes and anti-inflamatory activities from plant extract have been reported (Artani et al., 2006; Artanti et al., 2012; Rahmawati et al., 2014; Mustarichie et al., 2015). In this present study, we report the isolation and structure determinations of chemical constituents from the water soluble fraction of this plant growing on two different plant hosts, Tectona grandia L. f. (Family Lamiaceae) and Mangifera indica L. (Family Anacardiaceae), including a new furan-2carbonyl C-glucoside (1), a new alkyl glucoside (2) together with ten known compounds (3-12). 2. Results and discussion From the methanolic extract of the entire plant of D. pentandra growing on Tectona grandis, a new furan-2-carbonyl C-glucoside (1) and
⁎
a new alkyl glucoside (2) (Fig. 1) were isolated together with ten known compounds including, benzyl-O-β-D-glucopyranoside (3) (Miyase et al., 1987), benzyl-O-α-L-rhamnopyranosyl-(1 → 6)-β-D-glucopyranoside (4) (De Tommasi et al., 1996), benzyl-O-β-D-apiofuranosyl-(1 → 6)-β-Dglucopyranoside (icariside F2, 5) (Miyase et al., 1988), methyl gallate 3O-β-D-glucopyranoside (6) (Kuang et al., 1989), methyl gallate 3-O-(6′O-galloyl)-β-D glucopyranoside (7) (Park et al., 1993), (+)-catechin (8) (Agrawal et al., 1989), procyanidin B-1 (9) and procyanidin B-3 (10) (Tarascou et al., 2006), bridelionoside A (11) (Sueyoshi et al., 2006), and kiwiionoside (12) (Murai et al., 1992). All known compounds were identified by comparison of physical data with literature values and from spectroscopic evidence. Compound 1 was isolated as an amorphous powder. The molecular formula was determined to be C18H18O11 by HRESITOFMS (m/z: 409.0773 [M−H]−, calcd for C18H17O11, 409.0776). The NMR spectroscopic data (Table 1) indicated that this compound contained a 2furanyl group from the chemical shifts at δH 7.51 (1H, d, J = 3.5 Hz), 7.76 (1H, d, J = 1.5 Hz), and 6.53 (1H, dd, J = 3.5, 1.5 Hz), and from a set of the chemical shifts at δC 152.2, 123.0, 113.0, and 149.7 (Pouchet and Behnke, 1993); one carbonyl group from the chemical shift at δC 185.7; a C-β-glucopyranosyl unit from a set of the chemical shifts at δC 79.6, 72.7, 79.0, 71.2, 81.6 and 64.7; in addition to a galloyl moiety from the chemical shifts at δH 7.11 (2H, s) and δC 121.1, 110.2 (2C), 146.3 (2C), 139.7 and 168.2. The chemical shifts of this compound
Corresponding author at: Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand. E-mail address: [email protected] (T. Kanchanapoom).
http://dx.doi.org/10.1016/j.phytol.2017.05.024 Received 23 March 2017; Received in revised form 24 May 2017; Accepted 30 May 2017 1874-3900/ © 2017 Phytochemical Society of Europe. Published by Elsevier Ltd. All rights reserved.
Phytochemistry Letters 21 (2017) 90–93
P. Sahakitpichan et al.
O HO
1''
3''
HO
O
O
6'
HO HO
5''
HO
7''
O
O
6
O
2
OH
OH
3
HO HO
HO
5
1'
O
OH
4
HO
1''
7''
O
6'
HO HO
5''
OH O
O 1'
2
OH
OH
3 4
1
2 Fig. 1. Structures of compounds 1 and 2. Table 1 1 H and 13C NMR spectroscopic data of compound 1, in CD3OD (1H NMR, 400 MHz and 13 C NMR, 100 MHz). Position 2 3 4 5 6 1′ 2′ 3′ 4′ 5′ 6′ 1” 2”, 6” 3”, 5” 4” 7”
Proton
Carbon
7.51 (1H, d, J = 3.5 Hz) 6.53 (1H, dd, J = 3.5, 1.5 Hz) 7.76 (1H, d, J = 1.5 Hz) 4.41 3.76 3.62 3.55 3.76 4.62 4.42
(1H, (1H, (1H, (1H, (1H, (1H, (1H,
d, J = 9.4 Hz) dd, J = 9.4, 8.7 Hz) dd, J = 8.7, 8.7 Hz) dd, J = 8.7, 8.7 Hz) m) br d, J = 10.7 Hz) dd, J = 10.7, 5.2 Hz)
7.11 (2H, s)
O
OH
shifts of the galloyl moiety. This additional moiety was assigned to be located at C-6′ of the glucopyranosyl moiety due to the downfield shift of this carbon atom to δC 64.7. The assignment of the structure was confirmed by 2D NMR experiments. In the HMBC spectrum, the significant correlations were observed from H-1′ (δH 4.40) to C-2 (δC 80.2), and H-6′ (δH 4.38 and 4.57) to C-7″ (δC 168.3) (Fig. 2). The absolute configuration was not determined, however, the coupling constant of 1,2-diol moiety with J = 2.5 Hz suggested the relative configuration of the C-2/C-3 position to be erythro (Peng et al., 2011). Thus, the structure of compound 2 was identified to be butane-2,3-diol 2-(6′-O-galloyl)-O-β-glucopyranoside. From the methanolic extract of the entire plant, D. pentandra growing on a different host, Mangifera indica was also carried out. Eight compounds were isolated and elucidated to be the same compounds as previously reported from D. pentandra growing on Tectona grandis, scleropentaside F (1), benzyl-O-β-D-glucopyranoside (3), benzyl-O-α-Lrhamnopyranosyl-(1 → 6)-β-D-glucopyranoside (4), benzyl-O-β-D-apiofuranosyl-(1 → 6)-β-D-glucopyranoside (5), methyl gallate 3-O-β-D-glucopyranoside (6), methyl gallate 3-O-(6′-O-galloyl)-β-D-glucopyranoside (7), (+)-catechin (8), and procyanidin B-1 (9). The present study isolated 12 compounds from the water soluble fraction including a furan-2-carbonyl C-glucoside (1), an alkyl glucoside (2), benzyl glycosides (3–5), hydrolysable tannin (6, 7), a flavan (8), procyanidins (9–10) and megastigmane glycosides (11–12). Scleropentaside F (1) was a functional group analogue of scleropentasides A-E, previously reported from Scleropyrum pentandrum (Disadee et al., 2012) of the related family Santalaceae in the same order Santalales. This compound type, scleropentaside A, was also isolated from the parasitic plant, Dendrotrophe frutescens (Hou et al., 2013), of the family Santalaceae. An alkyl glucoside, butane-2,3-diol 2-(6′-O-galloyl)O-β-glucopyranoside (2) was related to butane-2,3-diol 2-O-β-glucopyranoside, isolated compound from Viscum coloratum (Kong et al., 1992) of the family Viscaceae within the same order Santalales. The remaining compound types (6–12) were quite common to find from plant sources. In a comparative evaluation of this plant grown on two different hosts, it is interesting that this parasitic plant showed the accumulation of the same compounds, suggesting that these secondary metabolites came from the process in itself, may not transferred from the plant hosts. However, the presence of constituents bearing galloyl moieties attached to C-6 of the glucopyranosyl unit as compounds 1, 2 and 7 seemed to be specific from this plant. These results might be useful for further chemotaxonomic studies of the related family in the order Santalales.
O 3''
O
Fig. 2. HMBC correlations of compound 2.
1
HO
OH
152.2 123.0 113.0 149.7 185.7 79.6 72.7 79.0 71.2 81.6 64.7 121.1 110.2 146.3 139.7 168.2
were related to those of our previous furan-2-carbonyl C-β-glucopyranoside (scleropentaside A), isolated from Scleropyrum pentandrum (Disadee et al., 2012), except for the presence of a set of addition signals for the galloyl moiety. This moiety was assigned to be located at C6′ of the glucopyranosyl unit since the appearance of this carbon atom to δC 64.7. Also, the HMBC correlation was observed from H-6′ (δH 4.62) to C-7″ (δC 168.2). Therefore, the structure of compound 1 was identified to be furan-2-carbonyl C-(6′-O-galloyl)-β-glucopyranoside, namely scleropentaside F. The name was given according to a functional group analogue of scleropentasides A–E. Compound 2 was isolated as an amorphous powder. Its molecular formula was determined to be C17H24O11 by HRESITOFMS (m/z: 403.1243 [M–H]−, calcd for C17H23O11, 403.1246). Inspection of the NMR spectroscopic data revealed the presence of butane-2,3-diol as an aglycone moiety from the chemical shifts of two methyls at δC 15.8 and 18,6; and two hydroxymethines at δC 80.2 and 71.8, along with one βglucopyranosyl unit and one galloyl moiety as compared to compound 7. The chemical shifts were similar to those of butane-2,3-diol 2-O-βglucopyranoside (Kitajima et al., 1998) except for a set of the chemical
3. Experimental 3.1. General procedures NMR spectra were recorded in MeOH-d4 or DMSO-d6 using a Bruker AV-300 (300 MHz for 1H NMR and 75 MHz for 13C NMR) spectrometer. MS values were obtained on a JEOL JMS-SX 102 spectrometer. Optical rotations were measured with a Jasco P-1020 digital polarimeter. For column chromatography (cc), Diaion HP-20 (Mitsubishi Chemical Industries Co. Ltd.), silica gel 60 (70–230 mesh, Merck), and RP-18 (50 μm, YMC) were used. HPLC (Jasco PU-980 pump) was carried out 91
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on an ODS column (20 × 250 mm i.d., YMC) with a Jasco RI-2031 refractive index detector. The flow rates were 6 mL/min. The spraying reagent used for TLC was 10% H2SO4 in H2O-EtOH (1:1, v/v).
Table 2 1 H and 13C NMR spectroscopic data of compound 2, in CD3OD (1H NMR, 300 MHz and 13 C NMR, 75 MHz). Position
Proton
Carbon
1 2 3 4 1′ 2′ 3′ 4′ 5′ 6′
1.18 3.69 3.43 1.12 4.40 3.24 3.46 3.66 3.55 4.57 4.38
15.8 80.2 71.8 18.6 102.4 74.9 77.8 71.3 75.5 64.7
3.2. Plant material The entire plants of Dendrophthoe pentandra (L.) Miq. growing on Tectona grandis L. f. (Family Lamiaceae) and Mangifera indica L. (Family Anacardiaceae) were collected from Bangkok in March 2011. Voucher specimens (TK-PSKKU-0078) were deposited in the Herbarium of the Faculty of Pharmaceutical Sciences, Khon Kaen University. 3.3. Extraction and isolation
1” 2”, 6” 3”, 5” 4” 7”
The air dried entire plant of D. pentandra (7.4 kg) growing on Tectona grandis were extracted three times with MeOH, and concentrated to dryness. The residue (454.0 g from 842.6 g) was suspended in H2O and partitioned with Et2O (each 1.0 L, 4 times). The water soluble fraction (213.9 g) was applied to a Diaion HP-20 column, and eluted with H2O, 50% aqueous MeOH and MeOH, successively. The fraction eluted with 50% aqueous MeOH (62.1 g) was subjected to silica gel cc using solvent systems EtOAc-MeOH (9:1, 8.0 L), EtOAc-MeOHH2O (40:10:1, 10.0 L), EtOAc-MeOH-H2O (70:30:3, 8.0 L) and EtOAcMeOH-H2O (6:4:1, 10.0 L), respectively to obtain eight fractions (I–VIII). Compound 8 (1.07 g) was precipitated from fraction I. Fraction II (12.7 g) was applies to a RP-18 column using a gradient solvent system, H2O-MeOH (90:10 → 20:80, v/v) to provide nine sub-fractions. Sub-fraction II-2 was purified by preparative HPLC-ODS using solvent system H2O-MeCN (90:10, v/v) to provide compound 10 (134.3 mg). Compound 7 (422.3 mg) was precipitated from sub-fraction II-4. Subfraction II-7 was purified by preparative HPLC-ODS with solvent system H2O-MeCN (88:12, v/v) to afford compound 6 (22.5 mg). Sub-fraction II-9 was purified by preparative HPLC-ODS with solvent system H2OMeCN (88:12, v/v) to provide compounds 1 (45.5 mg) and 9 (18.5 mg). Fraction III (2.3 g) was separated on a RP-18 column using solvent system, H2O-MeOH (90:10 → 20:80, v/v) to provide six sub-fractions. Sub-fraction III-3 was purified by preparative HPLC-ODS with solvent system H2O-MeCN (90:10, v/v) to provide compounds 2 (6.3 mg) and 3 (29.7 mg). Fraction IV (3.1 g) was applied to a RP-18 column using solvent system, H2O-MeOH (90:10 → 20:80, v/v) to give seven subfractions. Sub-fraction IV-3 was purified by preparative HPLC-ODS using solvent system H2O-MeCN (88:12, v/v) to afford compounds 4 (141.3 mg) and 5 (52.8 mg). Fraction V (14.2 g) was applies to a RP-18 column using a gradient solvent system, H2O-MeOH (90:10 → 20:80, v/ v) to provide nine sub-fractions. Sub-fraction V-6 was purified by preparative HPLC-ODS with solvent system H2O-MeCN (92:8, v/v) to obtain compounds 11 (40.1 mg) and 12 (9.0 mg). From the air dried entire plant of the second source, D. pentandra (2.5 kg) growing on Mangifera indica, was similarly extracted with MeOH and concentrated to dryness. This part (483.9 g) was suspended in H2O and partitioned with Et2O. The water layer was applied to a Diaion HP-20 column, and eluted with H2O, 50% aqueous MeOH and MeOH, successively. The portion eluted with 50% aqueous MeOH (65.5 g) was repeatedly chromatographed on a silica gel cc using solvent systems EtOAc-MeOH (9:1, 8.0 L), EtOAc-MeOH-H2O (40:10:1, 10.0 L), EtOAc-MeOH-H2O (70:30:3, 6.0 L) and EtOAc-MeOH-H2O (6:4:1, 11.0 L), respectively to provide eight fractions (A to H). Fraction A (4.2 g) was applies to a RP-18 column using a gradient solvent system, H2O-MeOH (90:10 → 20:80, v/v) to provide six sub-fractions. Sub-fraction A-1 was purified by preparative HPLC-ODS using solvent system H2O-MeCN (88:12, v/v) to provide compound 9 (208.7 mg). Sub-fraction A-2 was purified by preparative HPLC-ODS with solvent system H2O-MeCN (88:12, v/v) to provide compound 8 (2.5 g). Fraction B (11.0 g) was applies to a RP-18 column using a gradient solvent system, H2O-MeOH (90:10 → 20:80, v/v) to obtain nine subfractions. Sub-fraction B-2 was purified by preparative HPLC-ODS using
a
(3H, d, J = 6.1 Hz) (1H, dq, J = 7.2, 2.5 Hz) (1H, dq, J = 7.0, 2.5 Hz) (1H, d, J = 6.1 Hz) (1H, d, J = 7.7 Hz) (1H, dd, J = 9.4, 7.7 Hz) (1H)a (1H)a (1H, m) (1H, dd, J = 11.9, 2.1 Hz) (1H, dd, J = 11.9, 5.7 Hz)
7.10 (2H, s)
121.4 110.2 146.5 139.9 168.3
Chemical shifts were assigned by HMQC.
solvent system H2O-MeCN (90:10, v/v) to provide compound 6 (212.3 mg). Sub-fraction B-3 was purified by preparative HPLC-ODS with solvent system H2O-MeCN (88:12, v/v) to afford compound 1 (309.3 mg). Sub-fraction B-4 was purified by preparative HPLC-ODS with solvent system H2O-MeCN (88:12, v/v) to yield compound 3 (196.3 mg). Fraction C (3.6 g) was applied to a RP-18 column using solvent system, H2O-MeOH (90:10 → 20:80, v/v) to give seven subfractions. Sub-fraction C-3 was purified by preparative HPLC-ODS using solvent system H2O-MeCN (90:10, v/v) to provide compound 5 (162.2 mg). Fraction D (11.0 g) was applies to a RP-18 column using a gradient solvent system, H2O-MeOH (90:10 → 20:80, v/v) to provide eight sub-fractions. Sub-fraction D-2 was purified by preparative HPLCODS with solvent system H2O-MeCN (85:15, v/v) to obtain compound 7 (338.2 mg). Sub-fraction D-4 was purified by preparative HPLC-ODS with solvent system H2O-MeCN (90:10, v/v) to provide compound 4 (104.3 mg). 3.4. Scleropentaside F (1) Amorphous powder, [α]D27–21.1 (MeOH, c 1.00); 1H NMR (CD3OD) and 13C NMR (CD3OD): Table 1; Negative HRESITOFMS, m/z: 409.0773 (C18H17O11 required 409.0776). 3.5. Butane-2,3-diol 2-(6′-O-galloyl)-O-β-glucopyranoside (2) Amorphous powder, [α]D24–35.2 (MeOH, c 0.63); 1H NMR (CD3OD) and 13C NMR (CD3OD): Table 2; Negative HRESITOFMS, m/z: 403.1243 (C17H23O11 required 403.1246). Acknowledgements This research work was supported by the grant from Chulabhorn Research Institute, Khon Kaen University and Mahidol University. References Agrawal, P.K., Bansal, M.C., Porter, L.J., Foo, Y., 1989. Flavanoids. In: Agrawal, P.K. (Ed.), Carbon-13 NMR of Flavonoids. Elsevier, Amsterdam, pp. 432–496. Artani, N., Ma’arifa, Y., Hanafi, M., 2006. Isolation and identification of active antioxidant compound from star fruit (Averrhoa carambola) mistletoe (Dendrophthoe pentandra (L.) Miq.) ethanol extract. J. Appl. Sci. 6, 1659–1663. Artanti, N., Firmansyah, T., Darmawan, A., 2012. Bioactivities evaluation of Indonesian Mistletoes (Dendrophthoe pentandra (L.) Miq.) leaves extracts. J. Appl. Pharm. Sci. 2, 24–27. De Tommasi, N., Rastrelli, L., Cumanda, J., Speranza, G., Pizza, C., 1996. Aryl and triterpenic from Margyricarpus setosus. Phytochemistry 42, 163–167. Disadee, W., Mahidol, C., Sahakitpichan, P., Sitthimonchai, S., Ruchirawat, S.,
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Nguyen, H.H., Nguyen, C.H., Nguyen, C.K., Chu, D.K., Mai, A.H., 2010. Chemical constituents of Dendrophthoe pentandra (L.). Miq., (Loranthaceae). Tap Chi Hoa Hoc 48, 245–249. Nguyen, H.H., Nguyen, C.H., Nguyen, C.K., 2011. Study of chemical constituents of Dendrophthoe pentandra (L.). Miq. (Loranthaceae), parasitic plant on Artocarpus integrifolia and Annona squamosa. Tap Chi Hoa Hoc 49, 181–185. Park, J.C., Yang, H.S., Lee, S.H., 1993. A tannin compound isolated from the underground part of Rosa rugosa Thunb. Korean J. Pharmacogn. 24, 319–321. Peng, X.P., Wang, Y., Liu, P.-P., Hong, K., Chen, H., Yin, X., Zhu, W.-M., 2011. Aromatic compounds from the halotolerant fungal strain of Wallemia sebi PXP-89 in a hypersaline medium. Arch. Pharm. Res. 34, 907–912. Pouchet, C.J., Behnke, J., 1993. 1st ed. The Aldrich Library of 13C and 1H FTNMR Spectra, vol. 3 Aldrich Chemical Company, Inc., Wisconsin. Rahmawati, S.I., Ishimaru, K., Hou, D.-X., Hayashi, N., 2014. Antioxidant activity and phenolic content of mistletoe extracts following high-temperature batch extraction. Food Sci. Technol. Res. 20, 201–206. Sueyoshi, E., Liu, H., Matsunami, K., Otsuka, H., Shinzato, T., Aramoto, M., Takeda, Y., 2006. Bridelionosides A–F: megastigmane glucosides from Bridelia glauca f. balansae. Phytochemistry 2483–2493. Tarascou, I., Barathieu, K., Simon, C., Ducasse, M.-A., Andre, Y., Fouquet, E., Dufourc, E.J., de Freitas, V., Laguerre, M., Pianet, I., 2006. A 3D structural and conformational study of procyanidin dimers in water and hydro-alcoholic media as viewed by NMR and molecular modeling. Magn. Reson. Chem. 44, 868–880.
Kanchanapoom, T., 2012. Unprecedented furan-2-carbonyl C-glycosides and phenolic diglycosides from Scleropyrum pentandrum. Phytochemistry 74, 115–122. Hou, X., Sun, M., Gao, H., Xiao, K., 2013. Chemical constituents from stems of Dendrotrophe frutescens. Biochem. Syst. Ecol. 51, 156–159. Kitajima, J., Ishikawa, T., Tanaka, Y., 1998. Water-soluble constituents of fennel. I. Alkyl glycosides. Chem. Pharm. Bull. 46, 1643–1646. Kong, D.Y., Li, H.T., Luo, S.Q., 1992. Studies on the chemical components of Viscum coloratum. VIII. Isolation and structure of 3-β-D-glucopyranosyloxy-butanol-2. Yao Xue Xue Bao 27, 792–795. Kuang, H.-X., Kasai, R., Ohtani, K., Liu, Z.-S., Yuan, C.-S., Tanaka, O., 1989. Chemistry constituents of pericarps of Rosa davurica Pall.: a traditional Chinese medicine. Chem. Pharm. Bull. 37, 2232–2233. Miyase, T., Ueno, A., Takizawa, N., Kobayashi, H., Karasawa, H., 1987. Studies on the clycosides of Epimedium grandiflorum Morr. var. thunbergianum (Miq.) Nakai. I. Chem. Pharm. Bull. 35, 1109–1117. Miyase, T., Ueno, A., Takizawa, N., Kobayashi, H., Oguchi, H., 1988. Studies on the clycosides of Epimedium grandiflorum Morr. var. thunbergianum (Miq.) Nakai. III. Chem. Pharm. Bull. 36, 2475–2484. Murai, F., Tagawa, M., Ohishi, H., 1992. Absolute structure of kiwiionoside as a precursor of loliolide and actinidiolide from Actinidia chinensis. Planta Med. 58, 112–113. Mustarichie, R., Warya, S., Saptarini, N.M., Ramdhani, D., 2015. Total flavonoid content and anti-inflammatory properties of Indonesian mistletoe (Dendrophthoe pentandra (L.) Miq.) ethanol extract. World J. Pharm. Res. 4, 287–302.
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Contents lists available at ScienceDirect
Phytochemistry Letters journal homepage: www.elsevier.com/locate/phytol
Short communication
A furan-2-carbonyl C-glucoside and an alkyl glucoside from the parasitic plant, Dendrophthoe pentandra
MARK
Poolsak Sahakitpichana, Wannaporn Disadeea, Rada Buntawonga, Nitirat Chimnoia, ⁎ Somsak Ruchirawata, Tripetch Kanchanapooma,b, a b
Chulabhorn Research Institute, Kamphaeng Phet 6, Talat Bang Khen, Lak Si, Bangkok 10210, Thailand Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
A R T I C L E I N F O
A B S T R A C T
Keywords: Dendrophthoe pentandra Loranthaceae Furan-2-carbonyl C-glucoside scleropentaside F Alkyl glucoside
A new furan-2-carbonyl C-(6′-O-galloyl)-β-glucopyranoside (scleropentaside F, 1) and a new alkyl glucoside [butane-2,3-diol 2-(6′-O-galloyl)-O-β-glucopyranoside, 2] were isolated from the entire hemi-parasitic plant, Dendrophthoe pentandra growing on Tectona grandis together with ten known compounds including, benzyl-O-βD-glucopyranoside (3), benzyl-O-α-L-rhamnopyranosyl-(1 → 6)-β-D-glucopyranoside (4), benzyl-O-β-D-apiofuranosyl-(1 → 6)-β-D-glucopyranoside (5), methyl gallate 3-O-β-D-glucopyranoside (6), methyl gallate 3-O-(6′-Ogalloyl)-β-D-glucopyranoside (7), (+)-catechin (8), procyanidin B-1 (9) and procyanidin B-3 (10), bridelionoside A (11), and kiwiionoside (12). In addition, compounds 1, 3–9 were isolated from this species growing on the different host, Mangifera indica. The structure elucidations were based on physical data and spectroscopic evidence including 1D and 2D experiments.
1. Introduction Dendrophthoe pentandra (L.) Miq. (Thai name: Ka-Fak-Ma-Muang, Family Loranthaceae) is a hemi-parasitic plant, generally grown on a variety of host plants. It is used in Thai traditional medicine for treating hypertension and diabetes. Previous phytochemical investigation of this plant growing on Annona squamosa L. (Family Annonaceae) and Artocarpus heterophyllus Lam. (Syn. A. integrifolius L, f., Family Moraceae) reported the isolation of flavonoids, steroids and triterpenoid (Nguyen et al., 2010, 2011). In the biological properties, the antioxidant, anti-diabetes and anti-inflamatory activities from plant extract have been reported (Artani et al., 2006; Artanti et al., 2012; Rahmawati et al., 2014; Mustarichie et al., 2015). In this present study, we report the isolation and structure determinations of chemical constituents from the water soluble fraction of this plant growing on two different plant hosts, Tectona grandia L. f. (Family Lamiaceae) and Mangifera indica L. (Family Anacardiaceae), including a new furan-2carbonyl C-glucoside (1), a new alkyl glucoside (2) together with ten known compounds (3-12). 2. Results and discussion From the methanolic extract of the entire plant of D. pentandra growing on Tectona grandis, a new furan-2-carbonyl C-glucoside (1) and
⁎
a new alkyl glucoside (2) (Fig. 1) were isolated together with ten known compounds including, benzyl-O-β-D-glucopyranoside (3) (Miyase et al., 1987), benzyl-O-α-L-rhamnopyranosyl-(1 → 6)-β-D-glucopyranoside (4) (De Tommasi et al., 1996), benzyl-O-β-D-apiofuranosyl-(1 → 6)-β-Dglucopyranoside (icariside F2, 5) (Miyase et al., 1988), methyl gallate 3O-β-D-glucopyranoside (6) (Kuang et al., 1989), methyl gallate 3-O-(6′O-galloyl)-β-D glucopyranoside (7) (Park et al., 1993), (+)-catechin (8) (Agrawal et al., 1989), procyanidin B-1 (9) and procyanidin B-3 (10) (Tarascou et al., 2006), bridelionoside A (11) (Sueyoshi et al., 2006), and kiwiionoside (12) (Murai et al., 1992). All known compounds were identified by comparison of physical data with literature values and from spectroscopic evidence. Compound 1 was isolated as an amorphous powder. The molecular formula was determined to be C18H18O11 by HRESITOFMS (m/z: 409.0773 [M−H]−, calcd for C18H17O11, 409.0776). The NMR spectroscopic data (Table 1) indicated that this compound contained a 2furanyl group from the chemical shifts at δH 7.51 (1H, d, J = 3.5 Hz), 7.76 (1H, d, J = 1.5 Hz), and 6.53 (1H, dd, J = 3.5, 1.5 Hz), and from a set of the chemical shifts at δC 152.2, 123.0, 113.0, and 149.7 (Pouchet and Behnke, 1993); one carbonyl group from the chemical shift at δC 185.7; a C-β-glucopyranosyl unit from a set of the chemical shifts at δC 79.6, 72.7, 79.0, 71.2, 81.6 and 64.7; in addition to a galloyl moiety from the chemical shifts at δH 7.11 (2H, s) and δC 121.1, 110.2 (2C), 146.3 (2C), 139.7 and 168.2. The chemical shifts of this compound
Corresponding author at: Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand. E-mail address: [email protected] (T. Kanchanapoom).
http://dx.doi.org/10.1016/j.phytol.2017.05.024 Received 23 March 2017; Received in revised form 24 May 2017; Accepted 30 May 2017 1874-3900/ © 2017 Phytochemical Society of Europe. Published by Elsevier Ltd. All rights reserved.
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O HO
1''
3''
HO
O
O
6'
HO HO
5''
HO
7''
O
O
6
O
2
OH
OH
3
HO HO
HO
5
1'
O
OH
4
HO
1''
7''
O
6'
HO HO
5''
OH O
O 1'
2
OH
OH
3 4
1
2 Fig. 1. Structures of compounds 1 and 2. Table 1 1 H and 13C NMR spectroscopic data of compound 1, in CD3OD (1H NMR, 400 MHz and 13 C NMR, 100 MHz). Position 2 3 4 5 6 1′ 2′ 3′ 4′ 5′ 6′ 1” 2”, 6” 3”, 5” 4” 7”
Proton
Carbon
7.51 (1H, d, J = 3.5 Hz) 6.53 (1H, dd, J = 3.5, 1.5 Hz) 7.76 (1H, d, J = 1.5 Hz) 4.41 3.76 3.62 3.55 3.76 4.62 4.42
(1H, (1H, (1H, (1H, (1H, (1H, (1H,
d, J = 9.4 Hz) dd, J = 9.4, 8.7 Hz) dd, J = 8.7, 8.7 Hz) dd, J = 8.7, 8.7 Hz) m) br d, J = 10.7 Hz) dd, J = 10.7, 5.2 Hz)
7.11 (2H, s)
O
OH
shifts of the galloyl moiety. This additional moiety was assigned to be located at C-6′ of the glucopyranosyl moiety due to the downfield shift of this carbon atom to δC 64.7. The assignment of the structure was confirmed by 2D NMR experiments. In the HMBC spectrum, the significant correlations were observed from H-1′ (δH 4.40) to C-2 (δC 80.2), and H-6′ (δH 4.38 and 4.57) to C-7″ (δC 168.3) (Fig. 2). The absolute configuration was not determined, however, the coupling constant of 1,2-diol moiety with J = 2.5 Hz suggested the relative configuration of the C-2/C-3 position to be erythro (Peng et al., 2011). Thus, the structure of compound 2 was identified to be butane-2,3-diol 2-(6′-O-galloyl)-O-β-glucopyranoside. From the methanolic extract of the entire plant, D. pentandra growing on a different host, Mangifera indica was also carried out. Eight compounds were isolated and elucidated to be the same compounds as previously reported from D. pentandra growing on Tectona grandis, scleropentaside F (1), benzyl-O-β-D-glucopyranoside (3), benzyl-O-α-Lrhamnopyranosyl-(1 → 6)-β-D-glucopyranoside (4), benzyl-O-β-D-apiofuranosyl-(1 → 6)-β-D-glucopyranoside (5), methyl gallate 3-O-β-D-glucopyranoside (6), methyl gallate 3-O-(6′-O-galloyl)-β-D-glucopyranoside (7), (+)-catechin (8), and procyanidin B-1 (9). The present study isolated 12 compounds from the water soluble fraction including a furan-2-carbonyl C-glucoside (1), an alkyl glucoside (2), benzyl glycosides (3–5), hydrolysable tannin (6, 7), a flavan (8), procyanidins (9–10) and megastigmane glycosides (11–12). Scleropentaside F (1) was a functional group analogue of scleropentasides A-E, previously reported from Scleropyrum pentandrum (Disadee et al., 2012) of the related family Santalaceae in the same order Santalales. This compound type, scleropentaside A, was also isolated from the parasitic plant, Dendrotrophe frutescens (Hou et al., 2013), of the family Santalaceae. An alkyl glucoside, butane-2,3-diol 2-(6′-O-galloyl)O-β-glucopyranoside (2) was related to butane-2,3-diol 2-O-β-glucopyranoside, isolated compound from Viscum coloratum (Kong et al., 1992) of the family Viscaceae within the same order Santalales. The remaining compound types (6–12) were quite common to find from plant sources. In a comparative evaluation of this plant grown on two different hosts, it is interesting that this parasitic plant showed the accumulation of the same compounds, suggesting that these secondary metabolites came from the process in itself, may not transferred from the plant hosts. However, the presence of constituents bearing galloyl moieties attached to C-6 of the glucopyranosyl unit as compounds 1, 2 and 7 seemed to be specific from this plant. These results might be useful for further chemotaxonomic studies of the related family in the order Santalales.
O 3''
O
Fig. 2. HMBC correlations of compound 2.
1
HO
OH
152.2 123.0 113.0 149.7 185.7 79.6 72.7 79.0 71.2 81.6 64.7 121.1 110.2 146.3 139.7 168.2
were related to those of our previous furan-2-carbonyl C-β-glucopyranoside (scleropentaside A), isolated from Scleropyrum pentandrum (Disadee et al., 2012), except for the presence of a set of addition signals for the galloyl moiety. This moiety was assigned to be located at C6′ of the glucopyranosyl unit since the appearance of this carbon atom to δC 64.7. Also, the HMBC correlation was observed from H-6′ (δH 4.62) to C-7″ (δC 168.2). Therefore, the structure of compound 1 was identified to be furan-2-carbonyl C-(6′-O-galloyl)-β-glucopyranoside, namely scleropentaside F. The name was given according to a functional group analogue of scleropentasides A–E. Compound 2 was isolated as an amorphous powder. Its molecular formula was determined to be C17H24O11 by HRESITOFMS (m/z: 403.1243 [M–H]−, calcd for C17H23O11, 403.1246). Inspection of the NMR spectroscopic data revealed the presence of butane-2,3-diol as an aglycone moiety from the chemical shifts of two methyls at δC 15.8 and 18,6; and two hydroxymethines at δC 80.2 and 71.8, along with one βglucopyranosyl unit and one galloyl moiety as compared to compound 7. The chemical shifts were similar to those of butane-2,3-diol 2-O-βglucopyranoside (Kitajima et al., 1998) except for a set of the chemical
3. Experimental 3.1. General procedures NMR spectra were recorded in MeOH-d4 or DMSO-d6 using a Bruker AV-300 (300 MHz for 1H NMR and 75 MHz for 13C NMR) spectrometer. MS values were obtained on a JEOL JMS-SX 102 spectrometer. Optical rotations were measured with a Jasco P-1020 digital polarimeter. For column chromatography (cc), Diaion HP-20 (Mitsubishi Chemical Industries Co. Ltd.), silica gel 60 (70–230 mesh, Merck), and RP-18 (50 μm, YMC) were used. HPLC (Jasco PU-980 pump) was carried out 91
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on an ODS column (20 × 250 mm i.d., YMC) with a Jasco RI-2031 refractive index detector. The flow rates were 6 mL/min. The spraying reagent used for TLC was 10% H2SO4 in H2O-EtOH (1:1, v/v).
Table 2 1 H and 13C NMR spectroscopic data of compound 2, in CD3OD (1H NMR, 300 MHz and 13 C NMR, 75 MHz). Position
Proton
Carbon
1 2 3 4 1′ 2′ 3′ 4′ 5′ 6′
1.18 3.69 3.43 1.12 4.40 3.24 3.46 3.66 3.55 4.57 4.38
15.8 80.2 71.8 18.6 102.4 74.9 77.8 71.3 75.5 64.7
3.2. Plant material The entire plants of Dendrophthoe pentandra (L.) Miq. growing on Tectona grandis L. f. (Family Lamiaceae) and Mangifera indica L. (Family Anacardiaceae) were collected from Bangkok in March 2011. Voucher specimens (TK-PSKKU-0078) were deposited in the Herbarium of the Faculty of Pharmaceutical Sciences, Khon Kaen University. 3.3. Extraction and isolation
1” 2”, 6” 3”, 5” 4” 7”
The air dried entire plant of D. pentandra (7.4 kg) growing on Tectona grandis were extracted three times with MeOH, and concentrated to dryness. The residue (454.0 g from 842.6 g) was suspended in H2O and partitioned with Et2O (each 1.0 L, 4 times). The water soluble fraction (213.9 g) was applied to a Diaion HP-20 column, and eluted with H2O, 50% aqueous MeOH and MeOH, successively. The fraction eluted with 50% aqueous MeOH (62.1 g) was subjected to silica gel cc using solvent systems EtOAc-MeOH (9:1, 8.0 L), EtOAc-MeOHH2O (40:10:1, 10.0 L), EtOAc-MeOH-H2O (70:30:3, 8.0 L) and EtOAcMeOH-H2O (6:4:1, 10.0 L), respectively to obtain eight fractions (I–VIII). Compound 8 (1.07 g) was precipitated from fraction I. Fraction II (12.7 g) was applies to a RP-18 column using a gradient solvent system, H2O-MeOH (90:10 → 20:80, v/v) to provide nine sub-fractions. Sub-fraction II-2 was purified by preparative HPLC-ODS using solvent system H2O-MeCN (90:10, v/v) to provide compound 10 (134.3 mg). Compound 7 (422.3 mg) was precipitated from sub-fraction II-4. Subfraction II-7 was purified by preparative HPLC-ODS with solvent system H2O-MeCN (88:12, v/v) to afford compound 6 (22.5 mg). Sub-fraction II-9 was purified by preparative HPLC-ODS with solvent system H2OMeCN (88:12, v/v) to provide compounds 1 (45.5 mg) and 9 (18.5 mg). Fraction III (2.3 g) was separated on a RP-18 column using solvent system, H2O-MeOH (90:10 → 20:80, v/v) to provide six sub-fractions. Sub-fraction III-3 was purified by preparative HPLC-ODS with solvent system H2O-MeCN (90:10, v/v) to provide compounds 2 (6.3 mg) and 3 (29.7 mg). Fraction IV (3.1 g) was applied to a RP-18 column using solvent system, H2O-MeOH (90:10 → 20:80, v/v) to give seven subfractions. Sub-fraction IV-3 was purified by preparative HPLC-ODS using solvent system H2O-MeCN (88:12, v/v) to afford compounds 4 (141.3 mg) and 5 (52.8 mg). Fraction V (14.2 g) was applies to a RP-18 column using a gradient solvent system, H2O-MeOH (90:10 → 20:80, v/ v) to provide nine sub-fractions. Sub-fraction V-6 was purified by preparative HPLC-ODS with solvent system H2O-MeCN (92:8, v/v) to obtain compounds 11 (40.1 mg) and 12 (9.0 mg). From the air dried entire plant of the second source, D. pentandra (2.5 kg) growing on Mangifera indica, was similarly extracted with MeOH and concentrated to dryness. This part (483.9 g) was suspended in H2O and partitioned with Et2O. The water layer was applied to a Diaion HP-20 column, and eluted with H2O, 50% aqueous MeOH and MeOH, successively. The portion eluted with 50% aqueous MeOH (65.5 g) was repeatedly chromatographed on a silica gel cc using solvent systems EtOAc-MeOH (9:1, 8.0 L), EtOAc-MeOH-H2O (40:10:1, 10.0 L), EtOAc-MeOH-H2O (70:30:3, 6.0 L) and EtOAc-MeOH-H2O (6:4:1, 11.0 L), respectively to provide eight fractions (A to H). Fraction A (4.2 g) was applies to a RP-18 column using a gradient solvent system, H2O-MeOH (90:10 → 20:80, v/v) to provide six sub-fractions. Sub-fraction A-1 was purified by preparative HPLC-ODS using solvent system H2O-MeCN (88:12, v/v) to provide compound 9 (208.7 mg). Sub-fraction A-2 was purified by preparative HPLC-ODS with solvent system H2O-MeCN (88:12, v/v) to provide compound 8 (2.5 g). Fraction B (11.0 g) was applies to a RP-18 column using a gradient solvent system, H2O-MeOH (90:10 → 20:80, v/v) to obtain nine subfractions. Sub-fraction B-2 was purified by preparative HPLC-ODS using
a
(3H, d, J = 6.1 Hz) (1H, dq, J = 7.2, 2.5 Hz) (1H, dq, J = 7.0, 2.5 Hz) (1H, d, J = 6.1 Hz) (1H, d, J = 7.7 Hz) (1H, dd, J = 9.4, 7.7 Hz) (1H)a (1H)a (1H, m) (1H, dd, J = 11.9, 2.1 Hz) (1H, dd, J = 11.9, 5.7 Hz)
7.10 (2H, s)
121.4 110.2 146.5 139.9 168.3
Chemical shifts were assigned by HMQC.
solvent system H2O-MeCN (90:10, v/v) to provide compound 6 (212.3 mg). Sub-fraction B-3 was purified by preparative HPLC-ODS with solvent system H2O-MeCN (88:12, v/v) to afford compound 1 (309.3 mg). Sub-fraction B-4 was purified by preparative HPLC-ODS with solvent system H2O-MeCN (88:12, v/v) to yield compound 3 (196.3 mg). Fraction C (3.6 g) was applied to a RP-18 column using solvent system, H2O-MeOH (90:10 → 20:80, v/v) to give seven subfractions. Sub-fraction C-3 was purified by preparative HPLC-ODS using solvent system H2O-MeCN (90:10, v/v) to provide compound 5 (162.2 mg). Fraction D (11.0 g) was applies to a RP-18 column using a gradient solvent system, H2O-MeOH (90:10 → 20:80, v/v) to provide eight sub-fractions. Sub-fraction D-2 was purified by preparative HPLCODS with solvent system H2O-MeCN (85:15, v/v) to obtain compound 7 (338.2 mg). Sub-fraction D-4 was purified by preparative HPLC-ODS with solvent system H2O-MeCN (90:10, v/v) to provide compound 4 (104.3 mg). 3.4. Scleropentaside F (1) Amorphous powder, [α]D27–21.1 (MeOH, c 1.00); 1H NMR (CD3OD) and 13C NMR (CD3OD): Table 1; Negative HRESITOFMS, m/z: 409.0773 (C18H17O11 required 409.0776). 3.5. Butane-2,3-diol 2-(6′-O-galloyl)-O-β-glucopyranoside (2) Amorphous powder, [α]D24–35.2 (MeOH, c 0.63); 1H NMR (CD3OD) and 13C NMR (CD3OD): Table 2; Negative HRESITOFMS, m/z: 403.1243 (C17H23O11 required 403.1246). Acknowledgements This research work was supported by the grant from Chulabhorn Research Institute, Khon Kaen University and Mahidol University. References Agrawal, P.K., Bansal, M.C., Porter, L.J., Foo, Y., 1989. Flavanoids. In: Agrawal, P.K. (Ed.), Carbon-13 NMR of Flavonoids. Elsevier, Amsterdam, pp. 432–496. Artani, N., Ma’arifa, Y., Hanafi, M., 2006. Isolation and identification of active antioxidant compound from star fruit (Averrhoa carambola) mistletoe (Dendrophthoe pentandra (L.) Miq.) ethanol extract. J. Appl. Sci. 6, 1659–1663. Artanti, N., Firmansyah, T., Darmawan, A., 2012. Bioactivities evaluation of Indonesian Mistletoes (Dendrophthoe pentandra (L.) Miq.) leaves extracts. J. Appl. Pharm. Sci. 2, 24–27. De Tommasi, N., Rastrelli, L., Cumanda, J., Speranza, G., Pizza, C., 1996. Aryl and triterpenic from Margyricarpus setosus. Phytochemistry 42, 163–167. Disadee, W., Mahidol, C., Sahakitpichan, P., Sitthimonchai, S., Ruchirawat, S.,
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