Chemical constituents from Teucrium viscidum
Li Cheng1, Jing Chen2, Yan Tan1, Fuqian Wang4, Xuanbin Wang1,Yongbo Xue3, Xincai Hao1*, Yonghui Zhang3*
1. School of Pharmacy, Hubei University of Medicine, Shiyan 442000, China
2. Integrated tcm& western medicine dept, Shiyan Renmin Hospital, Shiyan 442008, China
3. Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
4. Department of Pharmacy, Wuhan First Hospital, Wuhan 430022, China
Abstract: A new monoterpenoid, 4,5,8-trihydroxy-6(7)-en-decenoic acid γ-lactone (1) and six known compounds, 3,7-dimethyloct-1-ene-3,6,7-triol (2), 2,8-bornanediol (3), 1-(4-hydroxyphenyl)ethane-1,2-diol (4),2-(3-methoxy-4-hydroxyphenyl)-propane-1,3-diol(5), indole-3-carboxylic acid (6), and 3-hydroxy-benzenemethanol (7) were isolated from the whole parts of Teucrium viscidum. Their structures were established by a combination of spectroscopic data analysis, besides comparison with literature data. Compounds 2–7 described above were isolated from this genus for the first time.
Keywords: Teucrium viscidum;Chemical constituents; Monoterpenoid; Structural identification
CLC number: R284 Document code: A Article ID: 1003–1057(2018)10–719–05
The genus Teucrium (Lamiaceae family), including over 300 species, is distributed all over the world, especially in the Mediterranean Basin. So far, terpenes, sterols, flavonoids, iridoids, polyphenolic compounds, saponins,essential oils and alkaloids have been found in this genus. Moreover, they have been found to have antioxidant, antimicrobial and anticancer activities[2–4]. Teucrium viscidum Blume (T. viscidum), an annual herb, is used as a traditional Chinese medicine (TCM) to treat pulmonary abscesses, hematemesis, hemoptysis, traumatic injuries and bites of rabies-stricken dogs or venomous snakes. In order to find novel bioactive products from TCM, a new triterpenoid 1 and six known compounds 2–7were isolated, 3,7-dimethyloct-1-ene-3,6,7-triol (2), 2,8-bornanediol (3), 1-(4-hydroxyphenyl)ethane-1,2-diol (4), 2-(3-methoxy-4-hydroxyphenyl)-propane-1,3-diol (5), indole-3-carboxylic acid (6), and 3-hydroxy-benzenemethanol (7). All the compounds(Fig. 1) were first isolated from the genus.
Figure 1. Chemical structures of compounds 1–7.
2.1. General procedures
The rotation luminosity was measured on a Perkin Elmer PE-341LC. IR spectra were recorded on a Bruker Vertex 70 FT-IR spectrophotometer. HRESI-MS data were recorded with API QSTAR Pulsar spectrometer. NMR spectra were measured using a Bruker AM-400 spectrometer, and the shifts of 1H NMR and 13C NMR were referenced by the solvent peaks for C5D5N at δH 8.74, 7.58, 7.22 and δC 150.35, 135.91, 123.87. Silica gel powder (200–300 mesh, Qingdao Marine Chemical Inc., Qingdao, China), Amberchrom CG161M (75 μm, Rohm and Haas Company, Philadelphia, PA, USA), ODS (50 μm, YMC, Japan) and Sephadex LH-20 (Pharmacia biotech Ab, Stockholm, Sweden) were used for column chromatography. The HPLC (Agilent 1100 pump, Agilent UV detector), couple with a YMC column (250 mm×10 mm, 5 μm) was employed in the present study. TLC was performed on a silicone GF254 board in UV light (254 nm or 356 nm) or with 95% ethanol sulfuric acid solution, and then spray spots were heated.
2.2. Plant materials
T. viscidum were collected in Shiyan City, Hubei Province of China, in June 2010. The plant was identified by Changgong Zhang (Huazhong University of Scienceand Technology). The voucher specimen (No. 20100616)has been deposited at the herbarium of Hubei Key Laboratory of Natural Medicinal Chemistry and ResourceEvaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology.
2.3. Extraction and isolation
The whole plants of T. viscidum were extracted with 70% acetone for three times at the room temperature. The extracts of acetone were concentrated in vacuum. The residue was suspended in water and respectively partitioned with petroleum ether (PE), CHCl3 and EtOAc to get PE section, CHCl3 section and EtOAc section,respectively. The EtOAc partition (150 g) was subjected to a silica gel column and eluted with CHCl3–MeOH (60:1–0:1, v/v) to produce five sub-fractions (F1-5).
F1 was separated with Sephadex LH-20 column and eluted with MeOH to afford three fractions (F1.1−1.3). F1.1 was subjected to RP-C18 gel and eluted with MeOH–H2O (1:4, v/v), after purified with semi-preparative HPLC (MeOH–H2O, 40:60, v/v) to afford compounds 1 (4 mg) and 2 (6 mg). Fraction 1.2 was separated with a Sephadex LH-20 column and eluted with MeOH to obtain compound 3 (9 mg).
F3 was subjected to a silica gel column and eluted with CHCl3–MeOH (16:1, v/v) to get sub-fractions F3.1 and F3.2. F3.1 was separated on Sephadex LH-20 column and eluted with MeOH to get fraction F3.1.1, fraction F3.1.2 and F3.1.3. Fraction F3.1.2 was further separated with semi-preparative HPLC (MeOH–H2O, 35:65, v/v) to afford compounds 4 (13 mg) and 5 (6 mg). Compound 6 (10 mg) was separated from F3.1.3 by ODS column and eluted with MeOH−H2O (30%−60%, v/v). Compound 7 (15 mg) was obtained from fraction F4 by ODS column and eluted with MeOH−H2O (25%−75%, v/v).
3. Structural identification
3.1. 4,?5,?8-?Trihydroxy-?6(7)-en-?decenoic acid γ-?lactone (1)
Compound 1 was yellow oil. Its molecular formula was determined to be C10H16O4 by HRESIMS atm/z 223.0930 [M+Na]+ (calcd. for C10H16O4 Na+, m/z 223.0941), revealing three degrees of unsaturation (Fig. 2). The IR spectrum indicated the presence of hydroxy group (3379 cm–1) and γ-lactone (1762 cm–1). The 1H NMR spectrum (Table 1) showed one tertiary methyl singlet (δH 0.88, t, J 7.6 Hz, H-10), three oxygenated methines(δH 4.46, ddd, J112.4Hz, J25.2Hz, J32.0 Hz, H-4;δH 4.11, t, J 6.4 Hz, H-5;δH 3.94,dd, J112.8Hz, J26.4 Hz, H-8) and two olefinic protons(δH 5.77, dd, J115.6Hz, J26.4 Hz, H-7;δH 5.65, dd, J115.6Hz, J26.4 Hz, H-6). In turn,the 13C NMR and DEPT spectra (Table 1) indicated the presence of an ester carbonyl (δC 180.4, C-1), two double bonds (δC 137.7, C-7; δC 129.4, C-6), three oxygenated methines (δC 84.9,C-4; δC 74.9, C-5; δC 74.4, C-8), three methylenes (δC 31.2, C-9; δC 29.5, C-2; δC 24.8, C-3) and one methyl (δC 10.3, C-10), suggesting that 1 was a chain compound with the double bound and lactone.
Figure 2. Thestructure of compound 1.
Table 1. 1H NMR (400 MHz) and 13C NMR (100 MHz) spectral data of compound 1in CD3OD (δ in ppm,J in Hz).
The1H-1H COSY (Fig. 3) showed correlations of C-2/C-3/C-4/C-5/C-6/ C-7/C-8/C-9/C-10. The correlationsof HMBC from H-7 (δH 5.77, dd, J115.6Hz, J26.4 Hz), H-6 (δH 5.65, dd, J115.6 Hz, J26.4 Hz) to C-8 (δc 74.4) and from H-5 (δH 4.11, t, J 6.4 Hz) to C-6 (δC 129.4) and C-7 (δC 137.7) showed the double bound between C-8 and C-5, The correlations of HMBC (Fig. 3) from H-2, H-3 to C-1 showed the presence of 1,4-γ-lactone. Therefore, HSQC, 1H-1H COSY, HMBC and NOESY analysis (Fig. 3) revealed that the structure of 1 was 4,?5,?8-?trihydroxy-?6(7)-en-?decenoic acid γ-?lactone.
Figure 3.1H-1H COSY and Key HMBC correlations of compound 1.
Colorless oil(pyridine); –25.2 (c = 1.0, pyridine), lit. (–22.0, MeOH); 1H NMR (C5D5N, 400 MHz) δH: 6.21 (1H, dd, J110.7 Hz, J217.3 Hz, H-2), 5.60 (1H, dd, J117.3 Hz, J22.0 Hz, H-1), 5.15 (1H, ddd, J110.8 Hz, J25.2 Hz, J32.0 Hz, H-1), 1.51 (3H, s, H3-10), 1.50 (1H, s, H3-8), 1.49 (3H, s, H3-9). 13C NMR (C5D5N,100 MHz) δC: 148.0 (C-2), 111.7(C-1), 80.3 (C-3), 73.3 (C-4), 73.1 (C-7), 41.6 (C-6), 29.2 (C-8), 26.6 (C-5), 26.6 (C-9), 26.4 (C-10). All the above data were consistent with those of3, 7-dimethyloct-1-ene-3,6,7-triol.
3.3. 2,8-Bornanediol (3)
Colorless oil (CHCl3); –22.2 (c = 0.05, pyridine); 1H NMR (CDCl3, 400 MHz) δH: 4.00 (1H, m, H-2), 3.68 (1H, d, J 10.8 Hz, H-8), 3.41 (1H, d, J 10.8 Hz, H-8), 2.25 (1H, m, H-3), 1.99 (1H, m, H-6), 1.87 (1H, t, J 4.4 Hz, H-4), 1.71 (1H, m, H-5), 1.31 (1H, m, H-3),1.26 (1H, m, H-2), 0.97 (3H, s, H3-9), 0.96 (1H, m, H-5), 0.87 (3H, s, H3-10). 13C NMR (CDCl3,100 MHz) δC: 77.4 (C-2), 66.3 (C-8), 52.9 (C-1), 49.7(C-7), 41.6 (C-4), 39.1 (C-3), 28.1 (C-5), 26.1 (C-6), 14.1 (C-10), 13.6 (C-9). All the above data were consistent with those of2,8-bornanediol.
3.4. 1-(4-Hydroxyphenyl)ethane-1,2-diol (4)
Colorless powder (CHCl3);1H NMR (CD3OD, 400 MHz) δH: 7.19 (2H, d, J 8.0 Hz, H-2′,6′), 6.67 (2H, d, J 8.0 Hz, H-3′,5′), 4.57 (1H, dd, J16.0 Hz, J26.0 Hz, H-1), 3.71 (2H, m, H-2). 13C NMR (CD3OD, 100 MHz) δ: 157.6 (C-4′), 133.3 (C-1′), 127.0 (C-2′,6′), 116.7 (C-3′,5′), 74.8 (C-1), 66.5 (C-2).All the abovedatawere consistent with those of 1-(4-hydroxyphenyl) ethane-1, 2-diol.
Oil (MeOH); –21.9 (c = 0.05, methol); 1H NMR (CD3OD, 400 MHz) δH: 6.91 (1H, s, H-2), 6.82 (1H, d, J 8.1 Hz, H-5), 6.61 (1H, d, J 8.1 Hz, H-6), 3.86 (3H, s, H-10), 3.86 (2H, m, H-8, H-9), 3.69 (2H, m, H-8, H-9), 2.85 (1H, m, H-7). 13C NMR (CD3OD,100 MHz)δC: 147.8 (C-3), 146.1(C-1), 145.9 (C-4), 120.1 (C-6), 115.3 (C-5), 112.1 (C-2), 64.91 (C-8, 9), 56.1 (C-10), 49.8 (C-7). All the above data were consistent with those of2-(3-methoxy-4-hydroxyphenyl)-propane-1,3-diol.
3.6. Indole-3-carboxylic acid (6)
White amorphous powder(MeOH); 1H NMR (CD3OD, 400 MHz) δ: 8.06 (1H, d, J 7.40 Hz, H-4), 7.90 (1H, s, H-2), 7.46 (1H, d, J7.60 Hz, H-7), 7.20 (2H, m, H-5/H-6).13C NMR (CD3OD, 100 MHz) δC: 108.8(C-3), 113.3 (C-7), 122.0 (C-5), 122.6(C-4), 123.5 (C-6), 127.8 (C-9), 133.5 (C-2), 138.0 (C-8), 169.6 (C-10). All the above data were consistent with those ofindole-3-carboxylic acid.
3.7. 3-Hydroxy-benzenemethanol (7)
Colorless needle crystal (MeOH); 1H NMR (CD3OD, 400 MHz) δ: 7.24 (1H, d, J7.2 Hz, H-5), 7.08 (1H, t, J7.2 Hz, H-2), 6.80 (1H, t,J 7.6 Hz, H-6), 6.75 (1H, d, J 8.0 Hz, H-4), 4.61 (2H, s, H2-7). All the above data were consistent with those of3-hydroxy-benzenemethanol.
This project was financially supported by Hubei Provincial Outstanding Young and Middle-aged Science and Technology Innovation Team Project (Grant No. T201813).
 Hao, X.C.; Zhang, J.W.; Zhan, G.Q.; Xue, Y.B.; Luo, Z.W.; Yao, G.M.; Zhang, Y.H. Chemical constituents from Teucrium viscidum.Biochem. Syst. Ecol. 2013, 51, 78–82.
 Vukovic, N.; Milosevic, T.; Sukdolak, S.; Solujic, S. Antimicrobial Activities of Essential Oil and Methanol Extract of Teucrium montanum. Evid. Based Complement. Alternat. Med. 2007, 4, 17–20.
 Ljubuncic1, P.; Dakwar, S.; Portnaya, I.; Cogan, Uri.; Azaizeh, H.; Bomzon, A. Aqueous extracts of Teucriumpolium possess remarkable antioxidant activity in vitro.Evid. Based Compl. Alternat.. 2006, 3, 329–338.
 Gao, C.; Han, L.; Zheng, D.; Jin, H.W.; Gai, C.Y.; Wang, J.B.; Zhang, H.; Zhang, L.R.; Fu, H.Z. Dimeric Abietane Diterpenoids and Sesquiterpenoid Lactones from Teucrium viscidum. J. Nat. Prod.2015, 78, 630−638.
 Kitajima, J.; Aoki, Y.; Ishikawa, T.; Tanaka, Y. MonoterpenoidPolyols in Fruit of Cnidium monnieri. Chem. Pharm. Bull.1998,46, 1580–1582.
 Weyerstahl, P.; Marschall Weyerstahl, H.; Kaul, V.K.; Manteuffel, E.; Glasow, L. Constituents of the Essential Oil of Strobilanthes auriculatus.Liebigs Ann. Chem.1987, 21–28.
 Hisamoto, M.; Kikuzaki, H.;Nakatani, N. Constituents of the Leaves of Peucedanum japonicum Thunb. and Their Biological Activity.J. Agric. Food Chem.2004, 52, 445–450
 Comte, G.; P.Allais, D.; J.Chulia, A.; Vercauteren, J.; Pinaud, N. Three phenylpropanoids from Juniperus phoenicea.Phytochemistry.1997, 44, 1169–1173.
 Wang, Y.; Hamalainen, A.; Tois, J.; Franzen, R. Preparationof indole-phosphine oxazoline (IndPHOX) ligands and their application in allylic alkylation. Tetrahedron Asymmetry.2010, 21, 2376–2384.
 Zhan R.; Liu Y.; Chen Y.G. Study on the Chemical Constituents from Pholidota protracta.J. Hainan Normal Uni. Nat. Prod. Res. Dev.2012, 24, 42–46.
程丽1, 陈静2, 谭艳1, 王富乾4, 汪选斌1, 薛永波3, 郝新才1*, 张勇慧3*
1. 湖北医药学院 药学院 武当特色中药研究湖北省重点实验室, 湖北 十堰442000
2.十堰市人民医院 中西医结合科,湖北 十堰 442008
3.华中科技大学同济医学院 药学院,湖北省天然药物化学与资源评价重点实验室,湖北 武汉 430030
4. 武汉市第一医院药学部, 湖北 武汉430022
摘要: 对香科科属植物血见愁进行化学成分研究,分离得到1个新化合物和6个已知化合物。通过波谱、理化常数以及比对文献资料的方法进行结构鉴定,分别为4,?8,?9-?trihydroxy-?6(7)-en-?decenoic acid γ-?lactone (1), 3,7-Dimethyloct-1-ene-3,6,7-triol (2), 2,8-Bornanediol (3), 1-(4-hydroxyphenyl)ethane-1,2-diol (4), 2-(3-methoxy-4-hydroxyphenyl)-propane-1,3-diol(5), indole-3-carboxylic acid (6) 和3-hydroxy-benzenemethanol (7), 化合物1–7均首次从该植物中分离得到。
关键词: 血见愁; 化学成分; 单萜; 结构鉴定
Received: 2018-05-26, Revised: 2018-07-18, Accepted: 2018-08-13.
Foundation item: Hubei Provincial Outstanding Young and Middle-agedScience and Technology Innovation Team Project (Grant No. T201813).
*Corresponding author. Tel.: +86-71-98891129; +86-27-83692311, Fax: +86-71-98891129; +86-27-83692762, E-mail: firstname.lastname@example.org; email@example.com