DSpace at VNU: Three new dammarane glycosides from Betula alnoides

Phytochemistry Letters (2011) 179–182 Contents lists available at ScienceDirect Phytochemistry Letters journal homepage: www.elsevier.com/locate/phytol Three new dammarane glycosides from Betula alnoides Minh Giang Phan a,*, Thi To Chinh Truong a, Tong Son Phan a, Katsuyoshi Matsunami b, Hideaki Otsuka b a b Faculty of Chemistry, College of Natural Science, Vietnam National University, Hanoi, 19 Le Thanh Tong Street, Hanoi, Viet Nam Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan A R T I C L E I N F O A B S T R A C T Article history: Received 26 December 2010 Received in revised form 16 February 2011 Accepted 25 February 2011 Available online 21 March 2011 Twenty compounds including three new dammarane glycosides, named betalnoside A (7), betalnoside B (8), and betalnoside C (11) were isolated from Betula alnoides Buch -Ham ex D Don (Betulaceae), of which 13 (1–13) were from the leaves, seven (14–20) from the stem bark, and three (2, 16, and 17) from the twigs Their structures were determined using spectroscopic analyses ß 2011 Phytochemical Society of Europe Published by Elsevier B.V All rights reserved Keywords: Betula alnoides Betulaceae Dammarane glycoside Introduction Results and discussion The genus Betula (Betulaceae) comprises more than 35 scientifically recognized species found in temperate and boreal zones of the northern hemisphere (Fuchino et al., 1995; Krasutsky, 2006) A comprehensive review (Krasutsky, 2006) revealed the concentration of lupanes (major) and oleananes (minor) in the outer bark of Betula plants Dammarane triterpenoids were reported predominantly from the leaves of Betula species such as B ermanii, B platyphylla var japonica, B maximowicziana, B davurica, B ovalifolia, and B schmidtii (Fuchino et al., 1995, 1996a,b, 1998a,b,c) The great number of occurrences of lupanes–oleananes in the outer bark and dammaranes in the leaves is considered to be significant due to their chemosystematic relevance There has been also an increase of chemosystematic interest in the phenolic (avonoid, lignan, and diarylheptanoid) constituents of the leaves (Keinaănen et al., 1999; Keinaănen and Julkune-Tiitto, 1998) and inner bark (Fuchino et al., 1995, 1996a,b, 1998a,b) of Betula species B alnoides Buch -Ham ex D Don (Betulaceae) is the only Betula species recorded in the Flora of Vietnam (Pham, 1993) The expected constituents lupeol, 3-O-acetoxyoleanolic acid, betulinic acid, and betulin were found in a previous report from the bark of B alnoides (Kamperdick et al., 1995) Our present study investigated the distribution of triterpenoids and flavonoids in the leaves, twigs, and stem bark of B alnoides Twenty compounds were isolated from B alnoides, of which 13 (1–13) were from the leaves, three (2, 16, and 17) from the twigs, and seven (14–20) from the stem bark Compounds 7, 8, and 11, named betalnosides A–C, are new dammarane glycosides The structures of the known compounds, pentacosanoic acid (1), bsitosterol (2) (Goad and Akihisha, 1997), ovalifoliolide B (3) (Fuchino et al., 1998b), rhamnocitrin (4) (Harborne, 1994), chrysoeriol (5) (Agrawal, 1989), 1-O-(tetracosanoyl)glycerol (6) (Sultana et al., 1999), b-sitosterol 3-O-b-D-glucopyranoside (9), quercetin 3-O-b-D-glucopyranoside (10) (Harborne, 1994), rutin (12) (Harborne and Mabry, 1982), quercetin (13) (Harborne, 1994), taraxeryl acetate (14) (Jin et al., 2007), taraxerone (15) (Sakurai et al., 1987), lupeol (16) (Fuchino et al., 1995), betulin (17) (Fuchino et al., 1995), betulinic acid (18) (Jin et al., 2007), oleanolic acid (19) (Fuchino et al., 1995), and ursolic acid (20) were determined by comparing their spectroscopic data (EIMS, HRESIMS, 1H, and 13C NMR) with the reported literature values or those of the authentic samples Compound was isolated as a white amorphous powder Its molecular formula was determined to be C35H60O7 by positive-ion HRESIMS (m/z 615.4230 [M+Na]+) The IR spectrum showed a hydroxyl absorption band at 3381 cmÀ1 Acid hydrolysis of with M HCl gave D-xylose, which was identified by HPLC analysis (Matsunami et al., 2009) In the 1H NMR spectrum of (Table 1) signals for eight tertiary methyl groups, of which three were linked to oxygenated carbons [dH 1.15 (3H, s), 1.17 (3H, s), and 1.19 (3H, s)], two oxygenated methine groups [dH 3.15 (1H, dd, J = 12.0 Hz, 4.5 Hz) and 3.77 (1H, t, J = 7.5 Hz)], and protons of a sugar moiety * Corresponding author Tel.: +84 38351439 E-mail address: phanminhgiang@yahoo.com (M.G Phan) 1874-3900/$ – see front matter ß 2011 Phytochemical Society of Europe Published by Elsevier B.V All rights reserved doi:10.1016/j.phytol.2011.02.011 M.G Phan et al / Phytochemistry Letters (2011) 179–182 180 Table 1 H (500 MHz) and C/H 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 10 20 30 40 50 13 C NMR (125 MHz) spectroscopic data of 7, 8, and 11 (CD3OD)a (CD3OD)a dc dH (J in Hz) dC dH (J in Hz) dC dH (J in Hz) 40.3 27.4 90.7 40.4 57.7 19.3 36.5 41.7 52.2 38.1 22.7 26.8 44.2 51.0 33.1 27.3 51.2 16.8 16.8 87.8 23.6 36.5 28.4 84.8 72.9 26.2 25.4 28.4 16.0 16.9 b-Xylose 107.4 75.5 78.0 71.3 66.7 0.99 1.71 3.15 – 0.81 1.51 1.32 – 1.41 – 1.29 1.66 1.83 – 1.11 1.25 1.67 1.01 0.91 – 1.16 1.73 1.81 3.77 – 1.17 1.15 1.05 0.86 0.93 s s s s s 0.99 1.71 3.15 – 0.81 1.51 1.32 – 1.40 – 1.32 1.69 1.84 – 1.10 1.29 1.74 1.02 0.91 – 1.14 1.30 1.60 3.96 – 4.82 1.74 1.05 0.86 0.93 s s s s s d (7.5) m t (9.0) m m, 3.84 dd (11.3, 5.5) 33.5 21.4 82.4 37.5 50.4 18.1 34.8 39.4 53.7 41.3 75.6 33.7 40.5 50.1 31.4 26.3 48.8 16.7 16.8 86.9 24.8 35.9 26.7 83.6 72.0 26.9 24.2 29.2 22.6 16.9 a-Arabinose 100.7 73.5 72.8 69.7 66.4 a-Arabinose 99.9 73.3 71.7 68.8 65.1 1.32 1.60 3.29 – 1.22 1.42 1.42 – 1.74 – 4.04 1.32 1.62 – 1.10 1.62 2.00 1.05 0.96 – 1.17 1.20 1.31 3.79 – 1.18 1.15 0.94 0.86 1.00 4.29 3.21 3.31 3.48 3.20 40.3 27.3 90.6 40.4 57.7 19.3 36.5 41.7 52.1 38.0 22.7 25.8 43.6 51.5 32.3 28.7 51.1 16.7 16.8 75.8 25.2 38.2 30.2 77.3 147.0 111.2 17.8 28.4 16.0 16.9 b-Xylose 107.4 75.5 77.9 71.3 66.7 4.26 3.55 3.45 3.74 3.45 d (7.5) m m m m, 3.95 m 4.28 3.55 3.52 3.84 3.25 d (7.5) m m m m, 3.95 m m, 1.71 m m, 1.82 m dd (12.0, 4.5) br d (11.4) m (1.58) m, 1.60 m m m, 1.52 m m m m, 1.53 m m, 1.89 m m s s s m m, 1.97 m t (7.5) 100 200 300 400 500 a 11a,b 4.29 3.21 3.31 3.48 3.20 m, 1.71 m m, 1.78 m dd (12.0, 4.5) br d (11.4) m, 1.58 m m, 1.60 m m m, 1.52 m m m m, 1.49 m m, 1.87 m m s s s m, 2.07 m m, 2.07 m t (5.2) br s, 4.93 br s br s s s s d (7.5) m t (9.0) ddd (10.0, 9.0, 5.5) m, 3.84 dd (11.5, 5.5) m m, 1.75 m br s m m m, 2.30 br d (14) m ddd (10.5, 10.5, 5.5) m, 2.48 m m m, 1.41 m m, 1.95 m m s s s m, 1.58 m m, 1.85 m t (7.0) Assignments were based on DEPT, HSQC, and HMBC (compound 11) spectra H NMR was measured in CDCl3 and 13C NMR in CD3OD + CDCl3 b (dH 3.20–4.29) were observed The 13C NMR spectrum of (Table 1) showed the presence of 35 signals After subtraction of five carbons for a xylopyranosyl moiety (dC 66.7, 71.3, 75.5, 78.0, and 107.4) (Fuchino et al., 1998c) 30 signals left belonged to a tetracyclic triterpenoid moiety containing an epoxide ring (dC 84.8 and 87.8) On the basis of the NMR data the aglycone of was identified as ocotillol (Fu et al., 2005) The xylopyranosyl moiety of was determined to be linked to C-3 of the aglycone on the basis of the significant downfield shift of C-3 (dC 90.7) on going from ocotillol (dC 79.0) The chemical shift of C-3 was also indicative of the 3aH orientation of (Li et al., 2007); glycosidation of the 3a-hydroxyl group caused a chemical shift to ca dC 82–83 of C-3 (Fuchino et al., 1996b) The coupling constant of the anomeric proton [dH 4.29 (1H, d, J = 7.5 Hz)] indicated the b configuration at C-10 for the xylose Therefore was determined to be 3-O-b-D-xylopyranosyl ocotillol (Fig 1) which was given a trivial name betalnoside A Compound was isolated as a white amorphous powder Its molecular formula was determined to be C35H60O7 by positive-ion HRESIMS (m/z 615.4229 [M+Na]+) The IR spectrum showed a hydroxyl absorption band at 3385 cmÀ1 Acid hydrolysis of with M HCl gave D-xylose, which was identified by HPLC analysis (Matsunami et al., 2009) The 1H and 13C NMR spectra of (Table 1) indicated that the structures of and differed only in the side chain at C-24 The side chain, which contained a tertiary (dC 75.8) and a secondary (dC 77.3) hydroxyl groups, two methylenes (dC 30.2 and 38.2), and an isopropenyl group (dC 17.8, 111.2, and 147.0), was determined as depicted in Fig (S2) by comparing its NMR data with those of 20(S),24(S)-dihydroxydammara-25-en-3one (Malinovskaya et al., 1980) and notopanaxoside A (Komakine et al., 2006) The absolute stereochemistries of C-20 and C-24 of could not be determined in this study Therefore was determined to be 3-O-b-D-xylopyranosyl 3b,20,24-trihydroxydammar-25-ene which was given a trivial name betalnoside B Compound 11 was isolated as a white amorphous powder Its molecular formula was determined to be C40H68O12 by positive-ion HRESIMS (m/z 763.4594 [M+Na]+) The IR spectrum showed a hydroxyl absorption band at 3392 cmÀ1 Acid hydrolysis of 11 with M HCl gave L-arabinose, which was identified by HPLC analysis (Matsunami et al., 2009) The 13C NMR spectrum of 11 (Table 1) showed the presence of 40 signals, of which 30 were assigned to an ocotillone-type aglycone (Fu et al., 2005) and ten to two arabinopyranosyl moieties (dC 66.4, 69.7, 72.8, 73.5, and 100.7; and 65.1, 68.8, 71.7, 73.3, and 99.9) (Fu et al., 2001) Accordingly, the signals observed at dC 82.4 and 75.6 were assigned to two glycosylated methines at C-3 and C-11, respectively, by comparing the 13C NMR spectroscopic data of 11 with those of 3-epi-ocotillol [()TD$FIG] M.G Phan et al / Phytochemistry Letters (2011) 179–182 181 R 12 19 O O 11 21 12 19 13 18 29 10 21 16 15 O HO OH O OH R = S1 R = S2 S2 = O OH 30 29 28 14 OH 17 OH O HO OH O 11 23 O 28 26 25 24 S1 = 30 OH 27 14 15 O OH 1' 22 16 2' 3' 18 10 O 5' HO HO 23 20 17 4' 13 26 25 24 O OH 27 11 22 HO 20 Fig Chemical structures of compounds 3, 7, 8, and 11 (Fuchino et al., 1996b) (A ring), 20(S),24(R)-epoxydammarane3a,11a,25-triol (Fuchino et al., 1995) (B, C, D rings, and the side chain), and their analogous compounds (Fuchino et al., 1995, 1996b) Based on the coupling constants of H-3 [dH 3.29 (1H, br s)] and H-11 [dH 4.04 (1H, ddd, J = 10.5 Hz, 10.5 Hz, 5.5 Hz)], H-3 and H-11 were assigned as a-oriented (Fig 1) On the basis of the NMR chemical shifts (Fu et al., 2005; Sugimoto et al., 2009) the absolute configurations at C-20 and C-24 of this ocotillone-type triterpenoid were determined as S and R, respectively The linkages of the sugar moieties were confirmed by HMBC correlations between H-10 (dH 4.26) and C-3, between H-3 and C-10 (dC 100.7), and between H-100 (dH 4.28) and C-11 (Fig 2) The a-anomeric configurations for the arabinoses were determined by their 3J coupling constant (7.5 Hz) between H-1 and H-2 Therefore 11 was determined to be 3,11-di-Oa-L-arabinopyranosyl 20(S),24(R)-epoxydammarane-3a,11a,25-triol which was given a trivial name betalnoside C Full 1H NMR assignments and the revised stereostructure of ovalifoliolide B (3) based on 2D NMR techniques (1H–1H COSY, HMQC, HMBC, and NOESY) were also reported by us The stereochemistry of the isopropenyl group at C-5 of was revised as b-oriented by the NOESY correlations between H-28a (dH 4.69) and H3-19 (dH 1.13) and between H3-29 (dH 1.73) and H-1b (dH 1.79) Experimental 3.1 General procedures Optical rotations were determined using a Jasco P-1030 digital polarimeter HRESIMS spectra were measured on a Thermo Fischer [()TD$FIG] OH OH O HO O OH OH O HO O OH Fig HMBC (H ! C) correlations of 11 O Scientific LTQ Orbitrap XL mass spectrometer 1H, 13C NMR, DEPT, H–1H COSY, HSQC, HMBC, and NOESY spectra were recorded on a Bruker Avance 500 NMR spectrometer Silica gel Merck 60 (Darmstadt, Germany) and Diaion HP-20 (Mitsubishi, Japan) were used for open-column chromatography (CC) and flash chromatography (FC) TLC was performed on precoated silica gel Merck 60 F254 plates 3.2 Plant materials The leaves, twigs, and stem bark of B alnoides Buch -Ham ex D Don (voucher specimen: No 426) were collected in June 2007 from district Dong Van, province Ha Giang, Vietnam by Dr Tran Ngoc Ninh of the Institute of Biological Resources and Ecology, Vietnam Academy of Science and Technology, Hanoi, Vietnam 3.3 Extraction and isolation The dried powdered leaves (580 g), the stem bark (270 g), and the twigs (800 g) of B alnoides were extracted separately with MeOH at room temperature The combined MeOH extracts were concentrated and then successively partitioned between water and organic solvents of increasing polarities to give n-hexane-, CH2Cl2-, EtOAc-, and n-BuOH-soluble fractions The leaves The n-hexane-soluble fraction (14 g) was subjected to silica gel CC (n-hexane–acetone 15:1 to 2:1) to give 13 fractions Fr (2.06 g) was washed with n-hexane to yield (18 mg) Fr (1.52 g) was subjected to silica gel CC (n-hexane–EtOAc 19:1, 9:1, and 4:1) to give (10.8 mg) Fr (1.74 g) was separated by silica gel CC (n-hexane–acetone 9:1, 6:1, and 4:1) to give (53.8 mg) The CH2Cl2-soluble fraction (27.6 g) was chromatographed by silica gel CC (n-hexane–acetone 15:1 to 2:1) to give five fractions Frs (0.95 g) and (2.3 g) were washed with n-hexane or acetone, respectively, to give (35.2 mg), (10.8 mg), and (143.5 g) The EtOAc-soluble fraction (9 g) was subjected to silica gel CC (CH2Cl2– MeOH 29:1 to 3:1) to give three fractions Fr (0.64 g) was separated by silica gel CC (CH2Cl2–EtOAc 9:1 to 2:1) and then purified by repeated silica gel FC (n-hexane–EtOAc, CH2Cl2–EtOAc, or CH2Cl2–MeOH gradients) to give a mixture of and (5.3 mg), (3.2 mg), (3 mg), (3.3 mg), and (13.9 mg) Fr (7.62 g) was chromatographed by silica gel CC (CH2Cl2–acetone 9:1 to 1:2) to give (28.3 mg), 10 (45.3 mg), and 11 (5.3 mg) The 1-BuOHsoluble fraction (5.5 g) was separated by Diaion HP-20 CC (MeOH– H2O 20%, 40%, and 60%) Compounds 12 (5 mg) and 13 (8.1 mg) were obtained from frs and eluted with MeOH–H2O 40% and MeOH–H2O 60%, respectively, by silica gel CC with CH2Cl2–MeOH 4:1 or 6:1 182 M.G Phan et al / Phytochemistry Letters (2011) 179–182 The stem bark The CH2Cl2-soluble fraction (9.21 g) was subjected to silica gel CC (n-hexane–acetone 29:1 to 4:1) to give six fractions Fr (0.15 g) was separated by silica gel CC (nhexane–CH2Cl2 29:1 and 19:1) to give 14 (16.2 mg) and 15 (22 mg) Fr (0.8 g) was washed with acetone to give 16 (3 mg) Fr (1.6 g) was chromatographed on silica gel (CH2Cl2–acetone 29:1 and 19:1) to give 17 (45.1 mg), 18 (20.9 mg), and a mixture of 19 and 20 (9.2 mg) The twigs The n-hexane-soluble fraction (2.4 g) was subjected to silica gel CC (n-hexane–acetone 19:1 to 2:1) to give seven fractions Fr (0.77 g) was chromatographed by silica gel CC (nhexane–acetone 90:1) to give 16 (4 mg) Fr (0.36 g) was washed with n-hexane to give (40 mg) The CH2Cl2-soluble fraction (7.87 g) was chromatographed twice by silica gel CC (CH2Cl2– EtOAc 19:1 to 4:1) to give 17 (3.5 mg) 3.3.1 Ovalifoliolide B (3) Colorless needles; ½aŠ24 D +92.3 (c 0.2, CHCl3); mp 196–198 8C; IR (film): nmax cmÀ1 3483, 1702, 1633, 1445, 1371, 1292, 1165, 1082, 1028; HRESIMS: m/z 495.34335 [M+Na]+, calc for C30H48O4Na: 495.34448; 1H NMR (CDCl3): d 0.93 (3H, s, H3-18), 0.95 (3H, s, H330), 1.12 (3H, s, H3-26), 1.13 (6H, s, H3-19, H3-21), 1.13 (1H, m, H15a), 1.20 (3H, s, H3-27), 1.22 (1H, m, H-7a), 1.39 (1H, t, J = 13.5 Hz, H-1a), 1.47 (1H, m, H-6a), 1.49 (1H, m, H-15b), 1.58 (1H, m, H-16a), 1.59 (1H, m, H-7b), 1.65 (1H, m, H-22a), 1.70 (1H, m, H-22b), 1.73 (2H, m, H-12a, H-13), 1.73 (3H, s, H3-29), 1.77 (2H, m, H-16b, H23a), 1.79 (1H, m, H-1b), 1.81 (1H, m, H-5), 1.82 (1H, m, H-9), 1.84 (1H, m, H-17), 1.86 (1H, m, H-23b), 1.91 (1H, m, H-6b), 2.38 (1H, t, J = 15.5 Hz, H-12b), 2.40 (1H, dd, J = 15.5 Hz, 8.0 Hz, H-2a), 2.60 (1H, dd, J = 15.5 Hz, 12.5 Hz, H-2b), 3,72 (1H, t, J = 7,0 Hz, H-24), 4.51 (1H, q, J = 8.5 Hz, H-11), 4.69 (1H, s, H-28a), 4.86 (1H, s, H28b) 3.3.2 Betalnoside A (7) White amorphous powder; ½aŠ24 D +0.83 (c 0.06, CH3OH); IR (film): nmax cmÀ1 3381, 1456, 1375, 1164, 1075, 1042; HRESIMS: m/z 615.4230 [M+Na]+, calc for C35H60O7Na 615.4231; 1H and 13C NMR: see Table 3.3.3 Betalnoside B (8) White amorphous powder; ½aŠ24 D +108 (c 0.03, CH3OH); IR (film): nmax cmÀ1 3385, 1455, 1374, 1164, 1070, 1042; HRESIMS: m/z 615.4229 [M+Na]+, calc for C35H60O7Na 615.4231; 1H and 13C NMR: see Table 3.3.4 Betalnoside C (11) White amorphous powder; ½aŠ24 D À4.58 (c 0.31, CH3OH); IR (film): nmax cmÀ1 3392, 1456, 1385, 1160, 1071, 1041; HRESIMS: m/z 763.4594 [M+Na]+, calc for C40H68O12Na 763.4603; 1H and 13C NMR: see Table 3.4 Sugar analysis Compound (about 500 mg) was heated in M HCl (1.0 ml) at 90 8C for h After cooling, the reaction mixture was extracted with EtOAc and the aqueous layer was subjected to HPLC analysis [column: Shodex Asahipak NH 2P-50 4E, F = 4.6 mm, L = 25 cm, mobile phase: MeCN–H2O (4:1, v/v), detection: optical rotation detector (JASCO 2090Plus), and flow rate: 1.0 ml/min] to detect Dxylose, which was identified by comparison of its retention time with that of authentic sample, D-xylose (tR: 8.6 min, positive optical rotation) HPLC analyses under the same conditions as above revealed the presence of D-xylose for and L-arabinose for 11 The sugars were identified by comparison of their retention times with those of authentic samples, L-arabinose (tR: 8.4 min, positive optical rotation) Acknowledgement This work was supported by the National Foundation for Science and Technology Development (NAFOSTED, Hanoi, Vietnam) References Agrawal, P.K (Ed.), 1989 Carbon-13 NMR of Flavonoids Elservier, Amsterdam Fuchino, H., Satoh, T., Tanaka, N., 1995 Chemical evaluation of Betula species in Japan I Constituents of Betula ermanii Chem Pharm Bull 43, 1937–1942 Fuchino, H., Konishi, S., Satoh, T., Yagi, A., Saitsu, K., Tatsumi, T., Tanaka, N., 1996a Chemical evaluation of Betula species in Japan II Constituents of Betula platyphylla var japonica Chem Pharm Bull 44, 1033–1038 Fuchino, H., Satoh, T., Tanaka, N., 1996b Chemical evaluation of Betula species in Japan III Constituents of Betula maximowicziana Chem Pharm Bull 44, 1748– 1753 Fuchino, H., Satoh, T., Shimizu, M., Tanaka, N., 1998a Chemical evaluation of Betula species in Japan V Constituents of Betula davurica Chem Pharm Bull 46, 166– 168 Fuchino, H., Satoh, T., Shimizu, M., Yokochi, M., Tanaka, N., 1998b Chemical evaluation of Betula species in Japan V Constituents of Betula ovalifolia Chem Pharm Bull 46, 169–170 Fuchino, H., Satoh, T., Hida, J., Terada, M., Tanaka, N., 1998c Chemical evaluation of Betula species in Japan VI Constituents of Betula schmidtii Chem Pharm Bull 46, 1051–1053 Fu, H., Koike, K., Zheng, Q., Mitsunaga, K., Jia, Z., Nikaido, T., Lin, W., Guo, D., Zhang, L., 2001 Fargoside A–F, triterpenoid saponins from Holboellia fargesii Chem Pharm Bull 49, 999–1002 Fu, L., Zhang, S., Li, N., Wang, J., Zhao, M., Sakai, J., Hasegawa, T., Mitsui, T., Kataoka, T., Oka, S., Kiuchi, M., Hirose, K., Ando, M., 2005 Three new triterpenes from Nerium oleander and biological activity of the isolated compounds J Nat Prod 68, 198–206 Goad, L.J., Akihisha, T., 1997 Analysis of Sterols Chapmann & Hall, London Harborne, J.B (Ed.), 1994 The Flavonoids Advances in Research since 1986 Chapman & Hall, London Harborne, J.B., Mabry, T.J (Eds.), 1982 The Flavonoids Advances in Research Chapman & Hall, London Jin, W.J., Cai, X.F., Na, M.K., Lee, J.J., Bae, K.H., 2007 Triterpenoids and diarylheptanoids from Alnus hirsuta inhibit HIF-1 in AGS cells Arch Pharm Res 30, 412– 418 Kamperdick, C., Thuy, T.T., Sung, T.V., Adam, G., 1995 Triterpenoids from Betula alnoides Planta Med 61, 486 Keinaănen, M., Julkune-Tiitto, R., 1998 High performance liquid chromatographic determination of flavonoids in Betula pendula and Betula pubescens leaves J Chromatogr 793, 370377 Keinaănen, M., Julkunen-Tiitto, R., Rousi, M., Tahvanainen, J., 1999 Taxonomic implications of phenolic variation in leaves of birch (Betula L.) species Biochem Syst Ecol 27, 243–254 Komakine, N., Okasaka, M., Takaishi, Y., Kawazoe, K., Murakami, K., Yamada, Y., 2006 New dammarane-type saponin from roots of Panax notoginseng J Nat Med 60, 135–137 Krasutsky, P.A., 2006 Birch bark research and development Nat Prod Rep 23, 919– 942 Li, Q., Yao, Z.H., Shi, Y.H., Liu, X., Yao, X.S., Ye, W.C., 2007 Determination of the threedimensional structure of gynoside A in solution using NMR and molecular modelling Molecules 3, 907–916 Malinovskaya, G.V., Novikov, V.L., Denisenko, V.A., Uvarova, N.I., 1980 A new triterpene from the leaves of Betula mandschurica Chem Nat Compd 16, 257–261 Matsunami, K., Otsuka, H., Kondo, K., Shinzato, T., Kawahata, M., Yamaguchi, K., Takeda, Y., 2009 Absolute configuration of (+)-pinorenol 4-O-[600 -O-galloyl]-bD-glucopyranoside, macarangiosides E, and F isolated from the leaves of Macaranga tanarius Phytochemistry 70, 1277–1285 Pham, H.H., 1993 Illustrated Flora of Vietnam Published by the author, Montreal Sakurai, N., Yaguchi, Y., Inoue, T., 1987 Triterpenoids from Myrica rubra Phytochemistry 26, 217–219 Sugimoto, S., Nakamura, S., Matsuda, H., Kitagawa, N., Yoshikawa, M., 2009 Chemical constituents from seeds of Panax ginseng: structure of new dammarane-type triterpene ketone, panaxadione, and HPLC comparisons of seeds and flesh Chem Pharm Bull 57, 283–287 Sultana, N., Armstrong, J.A., Waterman, P.G., 1999 Benzopyran derivatives from the aerial parts of Eriostemon rhomboideus Phytochemistry 52, 895–900  ... V.A., Uvarova, N.I., 1980 A new triterpene from the leaves of Betula mandschurica Chem Nat Compd 16, 257–261 Matsunami, K., Otsuka, H., Kondo, K., Shinzato, T., Kawahata, M., Yamaguchi, K., Takeda,... Saitsu, K., Tatsumi, T., Tanaka, N., 1996a Chemical evaluation of Betula species in Japan II Constituents of Betula platyphylla var japonica Chem Pharm Bull 44, 1033–1038 Fuchino, H., Satoh, T.,... evaluation of Betula species in Japan III Constituents of Betula maximowicziana Chem Pharm Bull 44, 1748– 1753 Fuchino, H., Satoh, T., Shimizu, M., Tanaka, N., 1998a Chemical evaluation of Betula