第一部分 菲律賓楠葉部之成份研究(II) 第二部分 香桂葉部之成份研究

Part I: Chemical investigation of the leaves of Machilus philippinensis (II) Part II: Chemical investigation of the leaves of Cinnamomum subavenium

10.6342/NTU.2011.02554

林曉青

菲律賓楠 ； 香桂 ； 甲型葡萄糖水解酶 ； Machilus philippinensis ； Cinnamomum subavenium ； α-glucosidase

國立臺灣大學藥學研究所學位論文

2011年

博士

李水盛

繁體中文

第一部分 菲律賓楠葉部之成份研究(II) 甲型葡萄糖水解酶為一種位在小腸刷狀緣的酵素，可將含1→4和1→6鍵結之葡萄糖聚合物之食物水解得到葡萄糖，因而抑制此酵素可減緩飯後血糖之上升，達到治療糖尿病的效果，其抑制劑使用於臨床治療糖尿病者有：acarbose、voglibose和miglitol等。 在我們先前的研究中顯示，自菲律賓楠葉部之二氯甲烷可溶部分分離出的兩個acylated flavonol monorhamnosides化合物對於甲型葡萄糖水解酶(Bacillus stearothermophilus, type IV)具有強抑制效果，由於乙酸乙酯和正丁醇可溶部分亦具抑制活性，因此本論文第一部分繼續探究這些部份之活性成分，共分離出21個成分，包括7個原花青素(2−8)和epicatechin (1)以及13個黃酮糖苷類(9−15, 19−21, 23, 25和26)。另外，應用液相層析-固相萃取-核磁共振儀連接技術，分析具有抑制活性的黃酮類混合物，又鑑定出5個黃酮糖苷類(16−18, 22和24)。其中，machiphilitannins A (7)、B (8)、kaempferol 3-O-(2-O-β-D-apiofuranosyl)-α-L -rhamnopyranoside (9)和kaempferol 3-O-(2-O-β-D-apiofuranosyl)-α-L- arabinofuranoside (10)為新天然物。對於甲型葡萄糖水解酶(type IV from Bacillus stearothermophilus)之活性測試顯示，化合物aesculitannin B (2)、7、8、quercetin 3-O-(6-O-α-L-rhamnopyranosyl)-β-D-galactopyranoside (13)和kaempferol 3-O-α-L-arabinopyranoside (23)之IC50分為3.5、31.3、18.4、19.5和19.0 μM。 第二部分 香桂葉部之成份研究 香桂為中型常綠喬木，分布於台灣海拔700至2100公尺的中部山區、中國、緬甸、柬埔寨、越南、馬來西亞和印度尼西亞等地。甲型葡萄糖水解酶在人類腸道中消化碳水化合物扮演著重要的角色，其抑制劑使用於臨床治療糖尿病者有acarbose和miglitol等。本研究以抑制活性為導向，利用Sephadex LH-20管柱、矽膠管柱、逆相層析管柱以及半製備高壓液相層析管柱自香桂葉部之酒精萃取物分離並鑑定出36個化合物，分別屬於dibenzocycloheptenes (27−29, 31, 32和34)、倍半萜類(35−43)、新木脂素(44)、苷類(45, 46和48)、苯乙醇(47)、黃酮類(49−59)、單寧類(3, 4)。其中，cinnasubavene A−H (27−34)、1β,6α,9β-trihydroxy-cis- eudesm-3-ene-6-O-β-D-glucopyranoside (39)以及其衍生物(40−43)和kaempferol-3-O- (4'-Z-p-coumaroyl)-α-L-rhamnopyranoside (57)為新天然物。

Part I: Chemical investigation of the leaves of Machilus philippinensis (II) α-Glucosidase is an enzyme which is located in the small intestine brush broader and responsible for digestion of dietary carbohydrate with α-(1→4) and (1→6) linkage. Inhibition of this enzyme could improve postprandial glucose control in the treatment of diabetes mellitus. Currently, α-glucosidase inhibitors, acarbose, voglibose and miglitol, are used in clinic. Our recent studies have revealed that two acylated flavonol monorhamnosides from the leaf of Machilus philippinensis Merr. (Lauraceae) displayed potent inhibitory activities against α-glucosidase (Bacillus stearothermophilus, type IV). Continuing investigation of the α-glucosidase inhibitors in the EtOAc and n-BuOH soluble fraction of the EtOH extract of the M. philippinensis leaf via the bioassay-guided approach, 21 compounds, including seven proanthocyanidins (2−8), epicatechin (1) and 13 flavonoid glycosides (9−15, 19−21, 23, 25, and 26), were isolated. Application of high performance liquid chromatography–solid phase extraction–nuclear magnetic resonance (HPLC–SPE–NMR) hyphenated technique in characterization of the active compounds in a fraction rich in flavonol glycosides led to the identification of five additional flavonol glycosides (16−18, 22 and 24). Of these, machiphilitannins A (7), B (8), kaempferol 3-O-(2-O-β-D-apiofuranosyl)-α-L -rhamnopyranoside (1) and kaempferol 3-O-(2-O-β-D-apiofuranosyl)-α-L -arabinofuranoside (2) are new natural products. Bioassay of the isolated compounds showed the IC50 value of aesculitannin B (2), 7, 8, quercetin 3-O-(6-O-α-L-rhamnopyranosyl)-β-D-galactopyranoside (13) and kaempferol 3-O-α-L-arabinopyranoside (23) to be 3.5, 31.3, 18.4, 19.5 and 19.0 μM, respectively. Part II: Chemical investigation of the leaves of Cinnamomum subavenium Cinnamomum subavenium Miq. (Lauraceae) is a medium-sized evergreen tree distributed at an attitude of 700 to 2100 meters in central mountains in Taiwan and found in central to south China, Burma, Cambodia, Vietnam, Malaysia, Indonesia. α-Glucosidase is an enzyme which is located in the small intestine brush broader and responsible for digestion of dietary carbohydrate. Currently, α-glucosidase inhibitors such as acarbose and miglitol are used in clinic. Guided by bioassay against α-glucosidase (Bacillus stearothermophilus, type IV), 36 compounds were characterized and isolated by Sephadex LH-20 column, silica gel column, Lobar RP-18 column, and semi-preparative RP-18 HPLC. They belong to dibenzocycloheptenes (27−29, 31, 32 and 34), sesquiterpenoids (35−43), neolignan (44), glycosides (45, 46 and 48), phenethnol (47), flavonoids (49−59) and tannins (3, 4). Among them, cinnasubavene A−H (27−34), 1β,6α,9β-trihydroxy-cis-eudesm -3-ene-6-O-β-D-glucopyranoside (39) and its four derivatives (40−43) and kaempferol-3-O- (4'-Z-p-coumaroyl)-α-L-rhamnopyranoside (57) are new natural products.

1. 1. Lee, S. S.; Lin, H. C.; Chen, C. K. Acylated flavonol monorhamnosides, α-glucosidase inhibitors, from Machilus philippinensis Merr. Phytochemistry 2008, 69, 2347–2353.
   連結：
2. 2. Seger, C.; Godejohann, M.; Tseng, L. H.; Spraul, M.; Girtler, A.; Sturm, S.; Stuppner, H. LC-DAD-MS/SPE-NMR hyphenation. A tool for the analysis of pharmaceutically used plant extracts: identification of isobaric iridoid glycoside regioisomers from Harpagophytum procumbens. Anal. Chem. 2005, 77, 878–885.
   連結：
3. 4. Komae, H., Hayashi, N. Terpenes from Actinodaphne, Machilus and Neolitsea species, Phytochemistry 1972 , 11, 1181–1182
   連結：
4. 5. Cheng, M. J.; Jayaprakasam, B.; Ishikawa, T.; Seki H.; Tsai, I. L.; Wang, J. J.; Chen, I. S. Chemical and Cytotoxic Constituents from the Stem of Machilus zuihoensis. Helv. Chim. Acta. 2002 , 85, 1909–1914.
   連結：
5. 6. Chung, Y. C.; Cheng, M. J.; Chiang, Y. J.; Baic, J. C.; Chiuc, C. T.; Lind, R. J.; Hsuie, Y. R.; Lo, W. L. Chemical constituents from the leaves of Machilus zuihoensis Hayata var. mushaensis (Lu) Y.C. Liu. Nat. Prod. Res. 2009, 23, 871–875.
   連結：
6. 7. Cheng, M. J.; Tsai, I. L.; Lee, S. J.; Jayaprakasam, B.; Chen, I. S. Steryl epoxide, secobutanolide and butanolides from the stem wood of Machilus zuihoensis Phytochemistry 2005, 66, 1180–1185.
   連結：
7. 8. Tsai, I. L.; Chen, J. H.; Duh, C. Y.; Chen, I. S. Cytotoxic neolignans and butanolides from Machilus obovatifolia. Planta Med. 2001, 67, 559–561.
   連結：
8. 9. Karikome, H.; Mimaki, Y.; Sashida, Y.; A butanolide and phenolics from Machilus thunbergii. Phytochemistry 1991, 30, 315–319.
   連結：
9. 10. Lee, S. S.; Lin, Y. S.; Chen, C. K. Three Adducts of Butenolide and Apigenin Glycoside from the Leaves of Machilus japonica. J. Nat. Prod. 2009, 72, 1249–1252.
   連結：
10. 11. Park, B.Y.; Min, B.S.; Kwong, O.K. Increase of caspase-3 activity by lignans from Machilus thunbergii in HL-60 cells. Biol. Pharm. Bull. 2004, 27, 1305–1307.
    連結：
11. 12. Tomita, M.; Lu, S. T.; Lan, P. K.; Lin, F. M. Studies on the alkaloids of Formosan lauraceous plants. V. alkaloids of litsea cubeba person. Yakugaku Zasshi. 1965, 85, 593–596.
    連結：
12. 13. Li, G.; Lee, C. S.; Woo, M. H.; Le, S. H.; Chang, H. W.; Son, J. K. Lignans from the bark of Machilus thunbergii and their DNA topoisomerases I and II inhibition and cytotoxicity. Biol. Pharm. Bull. 2004, 27, 1147–1150.
    連結：
13. 14. Yu, Y. U.; Kang, S. Y.; Park, H. Y.; Sung, S. H.; Lee, E. J.; Kim, S. Y.; Kim, Y. C. Antioxidant lignans from Machilus thunbergii protect CCl4-injured primary cultures of rat hepatocytes. J. Pharm. Pharmacol. 2000, 52, 1163–1170.
    連結：
14. 15. Ycitaka Sashida, H. S.; Oohara, M. Lignans from Machilus Thunbergii. Phytochemistry 1987, 26, 1513–1516.
    連結：
15. 16. Ma, C. J.; Sung, S. H.; Kim, Y. C. Neuroprotective lignans from the bark of Machilus thunbergii. Planta Med. 2004, 70, 79–80.
    連結：
16. 17. Moon, H. I.; Chung, H. J. Meso-dihydroguaiaretic acid from Machilus thunbergii SIEB et Zucc., and its effects on the expression of matrix metalloproteinase cause by ultraviolet irradiated cultured human keratinocyte cells (HaCaT). Biol. Pharm. Bull. 2005, 28, 2176–2179.
    連結：
17. 18. Miyazawa, M. ; Okuno, Y.; Oshiro, K.; Kasahara, H.; Shimamura, H.; Nakamura, S.; Kameoka, H. Suppression of the SOS-inducing activity of Trp-P-1 and aflatoxin B1 by Meso-dihydroguaiaretic acid from Machilus thunbergii in the Salmonella typhimurium test. Biosci. Biotech. Biochem. 1998, 62, 1425–1427.
    連結：
18. 19. Lairini, K.; Ruiz-Rubio, M. Detection of tomatinase from Fusarium oxysporum sp. lycopersici in infected tomato plants. Phytochemistry, 1998 , 48, 1371–1376.
    連結：
19. 20. Tsai, I. L.; Chen, J. H.; Duh, C. Y.; Chen, I. S. Cytotoxic neolignans from the stem wood of Machilus obovatifolia. Planta Med. 2000, 66, 403–407.
    連結：
20. 21. Hiroko, S.; Yutaka, S.; Oohara, M. Lignans from Machilus Thunbergii. Phytochemistry 1988, 27, 634–636.
    連結：
21. 22. Khanbabaee, K.; Ree, T. V. Tannins: classification and definition. Nat. Prod. Rep. 2001, 18, 641–649.
    連結：
22. 23. Morimoto, S.; Nonaka, G. I.; Nishioka, I. Tannins and realted compounds. XXXV. Proanthocyanidins with a doubly linked unit from the root bark of Cinnamomum sieboldii MEISNER. Chem. Pharm. Bull. 1985, 33, 4338–4345.
    連結：
23. 24. Lou, H.; Yuan, H., Ma, B.; Ren, D.; Ji, M.; Oka, S. Polyphenols from peanut skins and their free radical-scavenging effects. Phytochemistry 2004, 65, 2391–2399.
    連結：
24. 25. Lin, H. C.; Lee, S. S. Proanthocyanidins from the leaves of Machilus philippinensis. J. Nat. Prod. 2010, 73, 1375–1380.
    連結：
25. 26. Bilia, A. R.; Morelli, I.; Hamburger, M.; Hostettmann, K. Flavans and A-type proanthocyanidins from Prunus prostrate. Phytochemistry 1996, 43, 887–892.
    連結：
26. 27. Morimoto, S.; Nonaka, G. I.; Nishioka, I. Tannins and related compounds. LIX. Aesculitannins, novel proanthocyanidins with doubly-bonded structures from Aesculus hippocastanum L. Chem. Pharm. Bull. 1987, 35, 4717–4729.
    連結：
27. 28. Kamiya, K.; Watanabe, C.; Endang, H.; Umar, M.; Satake, T. Studies on the Constituents of bark of Parameria laevigata MOLDENKE. Chem. Pharm. Bull. 2001, 49, 551–557.
    連結：
28. 29. Kamiya, K.; Ohno, A.; Horii, Y.; Endang, H.; Umar, M.; Satake, T. A-type proanthocyanidins from the bark of Parameria laevigata, Heterocycles 2003, 60, 1697–1708.
    連結：
29. 30. Balde, A. M.; DeBruyne, T.; Pieters, L.; Kolodziej, H.; Berghe, D. V.; Claeys, M.; Vlietinck, A. Oligomeric proanthocysnidins possessing a boubly linked structure from Pavetta Owariensis. Phytochemistry 1995, 38, 719–723.
    連結：
30. 31. Haslam, E. Symmetry and promiscuity in proanthocyanidin biochemistry Phytochemistry 1977, 16, 1625–1640.
    連結：
31. 32. Abe, Y.; Shoji, T.; Kawahara, N.; Kamakura, H.; Kanda, T.; Goda, Y.; Ozeki, Y. Structural characterization of a procyanidin tetramer and pentamer from the apple by low-temperature NMR analysis Tetrahedron Lett. 2008, 49, 6413–6418.
    連結：
32. 33. Shoji, T.; Mutsuga, M.; Nakamura, T.; Kanda, T.; Akiyama, H.; Goda, T. Isolation and structural elucidation of some procyanidins from apple by low-temperature nuclear magnetic resonance. J. Agric. Food Chem. 2003, 51, 3806–3813.
    連結：
33. 34. Muranaka, A.; Yoshida, K.; Shoji, T.; Moriichi, N.; Masumoto, S.; Kanda, T.; Ohtake, Y.; Kobayashi, N. Chiral recognition of apple procyanidins by complexation with oxotitanium phthalocyanine. Org. Lett. 2006, 8, 2447–2450.
    連結：
34. 35. Anderson, R. A.; Broadhurst, C. L.; Polansky, M. M.; Schmidt, W. F.; Khan, A.; Flanagan, V. P.; Schoene, N. W.; Graves, D. J. Isolation and characterization of polyphenol type-A polymers from cinnamon with insulin-like biological activity. J. Agric. Food Chem. 2004, 52, 65–70.
    連結：
35. 36. Lee, Y. A.; Cho, E. J.; Yokozawa, T. Effects of proanthocyanidin preparations on hyperlipidemia and other biomarkers in mouse model of type 2 diabetes J. Agric. Food Chem. 2008, 56, 7781–7789.
    連結：
36. 37. Liu, X. M.; Wei, J. P.; Tan, F. S.; Zhou, S. M.; Wurthwein, G.; Rohdewald, P. Antidiabetic effect of Pycnogenol French maritime pine bark extract in patients with diabetes type II. Life Sci. 2004, 75, 2505–2513.
    連結：
37. 38. Schafer, A.; Hogger, P. Oligomeric procyanidins of French maritime pine bark extract (Pycnogenol) effectively inhibit α-glucosidase. Diabetes Res. Clin. Pract. 2007, 77, 41–46.
    連結：
38. 39. H. C. Lin; S. F. Tsai; S. S. Lee. Flavonoid glycosides from the leaves of Machilus philippinensis. J. Chin. Chem. Soc. 2011, 58, in press
    連結：
39. 40. Chang, Y. C.; Chang, F. R.; Wu, Y. C. The constituents of Lindera glauca. J. Chin. Chem. Soc. 2000, 47, 373-380.
    連結：
40. 42. Oyama, K.; Kondo, T. Total synthesis of apigenin 7,4’-di-O-β-glucopyranoside, a component of blue flower pigment of Salvia patens, and seven chiral analogues Tetrahedron 2004, 60, 2025–2034.
    連結：
41. 43. Lee, S.-S.; Wang, J.-S.; Chen, K. C. S. Chemical constituents from the roots of Zizyphus jujube Mill. var. Spinosa (I). J. Chin. Chem. Soc. 1995, 42, 77–82.
    連結：
42. 44. Lu, Y. R.; Foo, L. Y. The polyphenol constituents of grape pomace. Food Chem. 1999, 65, 1–8.
    連結：
43. 45. de Almeida, A. P.; Miranda, M.; Simoni, I. C.; Wigg, M. D.; Lagrota, M. H. C.; Costa, S. S. Flavonol monoglycosides isolated from the antiviral fractions of Persea Americana (Lauraceae) leaf infusion. Phytother. Res. 1998, 12, 562–567.
    連結：
44. 46. Braca, A.; Politi, M.; Sanogo, R.; Sanou, H.; Morelli, I.; Pizza, C.; De Tommasi, N. Chemical composition and antioxidant activity of phenolic compounds from wild and cultivated Sclerocarya birrea (Anacardiaceae) leaves. J. Agric. Food Chem. 2003, 51, 6689–6695.
    連結：
45. 47. Rodrigues, E. D.; da Silva, D. B.; de Oliveira, D. C. R.; da Silva, G. V. DOSY NMR applied to analysis of flavonoid glycosides from Bidens sulphurea. J. Magn. Reson. Chem. 2009, 47, 1095–1100.
    連結：
46. 48. Wang, P. H.; Lee, S. S. Polar chemical constituents from Phoebe formosana. J. Chin. Chem. Soc. 1999, 46, 215–219.
    連結：
47. 49. Kadota, S.; Takamori, Y.; Nyein, K. N.; Kikuchi, T.; Tanaka, K.; Ekimoto, H. Constituents of the leaves of Woodfordia fruticosa KKURZ. I. Isolation, structure, and proton and carbon-13 nuclear magnetic resonance signal assignment of Woodfruticosin (Woodfordin C), an inhibitor of deoxyribonucleic acid topoisomerase II. Chem. Pharm. Bull. 1990, 38, 2687–2697
    連結：
48. 50. Hasan, A.; Ahmed, I.; Jay, M.; Voirin, B. Flavonoids glycosides and an anthraquinone from Rumex Chalepensis. Phytochemistry 1995, 39, 1211–1213.
    連結：
49. 51. Julião, L. S.; Piccinelli, A. L.; Marzocco. S.; Leitão, S. G.; Lotti, C.; Autore, G.; Rastrelli, L. Phenylethanoid glycosides from Lantana fucata with in Vitro Anti-inflammatory Activity. J. Nat. Prod. 2009, 72, 1424–1428.
    連結：
50. 52. Ishii, T.; Yanagisawa, M. Synthesis, separation and NMR spectral analysis of methyl apiofuranosides. Carbohydr. Res. 1998, 313, 189–192.
    連結：
51. 53. 林曉青，'菲律賓楠抑制甲型葡萄糖水解酶之活性成份研究'，國立台灣大學藥學研究所碩士論文，2006。
    連結：
52. 54. Rao, L.J.M.; Yada, H.; Ono, H.; Yoshida, M. Acylated and non-acylated flavonol monoglycosides from the Indian minor spice nagkesar (Mammea longifolia). J. Agri. Food Chem. 2002, 50, 3143–3146.
    連結：
53. 3. Shintre, V. P., Rao, S. B. Essential oil from leaves of Cinnamomum zeylanicum Breyn. J. Indian. Institute Sci. 1932, 15a, 84−87.
    連結：
54. 5. Chen, F. C.; Peng, C. F.; Tsai, I. L.; Chen, I. S. Antitubercular constituents from the stem wood of Cinnamomum kotoense. J. Nat. Prod. 2005, 68, 1318−1323.
    連結：
55. 6. Fujita, Y; Yamashita, T. Biochemistry of the Essential Oils of Cinnamomum micranthum Hay. 2 Nippon Kagaku Kaishi 1944, 65, 591.
    連結：
56. 7. Kuo, S. Y.; Hsieh, T. J.; Wang, Y. D.; Lo, W.L.; Hsui, Y. R.; Chen, C. Y. Cytotoxic constituents from the leaves of Cinnamomum subavenium. Chem. Pharm. Bull. 2008, 56, 97−101.
    連結：
57. 8. Isogais, A.; Murakoshia, H.; Suzuki, K. I.; Tamura, S. Chemistry and Biological Activities of Cinnzeylanine and Cinnzeylanol, New Insecticidal Substances from Cinnamonum zeylanicum Nees. Agric. Biol. Chem. 1977, 41, 1779−1783.
    連結：
58. 9. Lin, R. J.; Cheng, M. J.; Huang, J. C.; Lo, W. L.; Yeh, Y. T.; Yen, C. M.; Lu, C. M.; Chen, C. Y. Cytotoxic compounds from the stems of Cinnamomum tenuifolium. J. Nat. Prod. 2009, 72, 1816−1824.
    連結：
59. 10. Chen, C. H.; Lo, W. L.; Liu, Y. C.; Chen, C. Y. Chemical and cytotoxic constituents from the leaves of Cinnamomum kotoense. J. Nat. Prod. 2006, 69, 927−933.
    連結：
60. 11. Lin, I. J.; Lo, W. L.; Chia, Y. C.; Huang, L. Y.; Cham, T. M.; Tseng, W. S.; Yeh, Y. T.; Yeh, H. C.; Wang, Y. D.; Chen, C. Y. Isolation of new esters from the stems of Cinnamomum reticulatum Hay. Nat Prod Res. 2010, 24, 775−80.
    連結：
61. 12. Chen, C.; Wang, H.; Chung, S.; Lo, W.; Yang, W.; Yang, S. Chem. Nat. Comp. Chemical constituents from the roots of Cinnamomum subavenium. 2010, 46, 474−477.
    連結：
62. 13. Chen, C. Y.; Chen, C. H.; Wong, C. H.; Liu, Y. W.; Lin, Y. S.; Wang, Y. D.; Hsui, Y. R. Cytotoxic constituents of the stems of Cinnamomum subavenium. Nat. Prod. 2007, 70, 103−106.
    連結：
63. 14. Chen, C. Y.; Liu. T. Z.; Chen, C. H.; Wu, C. C.; Cheng, J. T.; Yiin, S. J.; Shih, M. K.; Wu, M. J.; Chern, C. L. Isoobtusilactone A-induced apoptosis in human hepatoma Hep G2 cells is mediated via increased NADPH oxidase-derived reactive oxygen species (ROS) production and the mitochondria-associated apoptotic mechanisms. Food Chem. Toxicol. 2007, 45, 1268−1276.
    連結：
64. 15. Chen, C. Y.; Yeh, H. C. A new amide from the stems of Cinnamomum reticulatum Hay. Nat. Prod. Res. 2011, 25, 26−30.
    連結：
65. 16. Hsieh, T. J.; Su, C. C.; Chen, C. Y.; Liou, C. H.; Lu, L. H. Using experimental studies and theoretical calculations to analyze the molecular mechanism of coumarin, p-hydroxybenzoic acid, and cinnamic acid." J. Mol. Struct. 2005, 741, 193–199.
    連結：
66. 17. Tsuji-Naito, K. Aldehydic components of cinnamon bark extract suppresses RANKL-induced osteoclastogenesis through NFATc1 downregulation. Bioorg. Med Chem. 2008, 16, 9176–9183.
    連結：
67. 18. Chao, L. K.; Hua, K. F.; Hsu, H. Y.; Cheng, S. S.; Lin, I. F.; Chen, C. J.; Chen, S. T.; Chang, S. T. Cinnamaldehyde inhibits pro-inflammatory cytokines secretion from monocytes/macrophages through suppression of intracellular signaling. Food. Chem. Toxicol. 2008, 46, 220–231.
    連結：
68. 19. Jayaprakasha, G. K.; Ohnishi-Kameyama, M.; Ono, H.; Yoshida, M.; Jaganmohan, R. L. Phenolic constituents in the fruits of Cinnamomum zeylanicum and their antioxidant activity. J. Agric. Food Chem. 2006, 54, 1672–1679.
    連結：
69. 20. Chen, C. Y.; Yang, W. L.; Hsui, Y. R. A novel sesquiterpenoid from the roots of Cinnamomum subavenium. Nat. Prod. Res. 2010, 24, 423–427.
    連結：
70. 21. Fang, S. H.; Rao, Y. K.; Tzeng, Y. M. Inhibitory effects of flavonol glycosides from Cinnamomum osmophloeum on inflammatory mediators in LPS/IFN-γ -activated murine macrophages. Bioorg. Med. Chem. 2005, 13, 2381–2388.
    連結：
71. 22. Kuo, Y. C.; Lu, C. K.; Huang, L. W.; Kuo, Y. H.; Chang, C.; Hsu, F. L.; Lee, T. H. Inhibitory effects of acylated kaempferol glycosides from the leaves of Cinnamomum kotoense on the proliferation of human peripheral blood mononuclear cells. Planta Med. 2005, 71, 412–415.
    連結：
72. 23. Nonaka, G.; Morimoto, S.; Nishioka, I. Tannins and related compounds. Part 13. Isolation and structures of trimeric, tetrameric, and pentameric proanthicyanidins from cinnamon. J. Chem. Soc., Perkin Trans. 1, 1983, 2139–2145.
    連結：
73. 24. Balde, A. M.; Pieters, T. B.; Kolodziej, H.; Berghe, D. V.; Claeys, M.; Vlietinck, A. Oligomeric proanthocyanidins possessing a doubly linked structure from Pavetta owariensis. Phytochemistry 1995, 38, 719–723.
    連結：
74. 25. Uchiyama, H.; Nagasawa, K. Determination of the distribution of D-glucuronic acid units within the chain of pig-skin dermatan sulfate near the linkage region. Carbohydr. Res. 1987, 159, 263–273.
    連結：
75. 26. Tsuzuki, Y..; Kataoka, S.; Funayama, M.; Satsumabayashi, K. Rotatory dispersion and stereochemistry of organic compounds. XVI. carbonylphenyl Glucosides. Bull. Chem. Soc. Jpn. 1971, 44, 526−532.
    連結：
76. 27. Craig, J. C.; Pereira, W. E.; Halpern, B.; Westley, J. W. Optical rotatory dispersion and absolute configuration—XVII: α-alkylphenylacetic acids. Tetrahedron 1971, 27, 1173−1184.
    連結：
77. 29. Bnnenberg, E.; Djerassi, C.; Mislow, K.; Moscowitz, A. Inherently dissymmetric chromophores and circular dichroism. J. Am. Chem. Soc. 1962, 84, 2823−2827.
    連結：
78. 30. Mislow, K.; Bunnenberg, E.; Records, R.; Wellman, K.; Djerassi, C. Inherently dissymmetric chromophores and circular cichroism. II. J. Am. Chem. Soc. 1963, 85, 1342−1349.
    連結：
79. 31. Joshua, H.; Gans, R.; Mislow, K. Stereochemistry of 9-dimethylamino-9,10- dihydro-4,5-dimethylphenanthrene. J. Am. Chem. Soc. 1968, 90, 4884−4892.
    連結：
80. 32. Suzuki, H. Electronic Absorption Spectra and Geometry of Organic Molecules, Academic Press, New York, 1967, p 262.
    連結：
81. 33. Rashidi, P.; Sandström, J. The UV and CD spectra of a 60 twisted bridged biphenyl: an experimental and CNDO/S study. J. Mol. Struct. 1991, 246, 25−32.
    連結：
82. 34. Sagiv, J.; Yogev. A.; Mazur, Y. Application of linear dichroism to the analysis of electronic absorption spectra of biphenyl, fluorene, 9,9'-spirobifluorene, and [6.6]vespirene. Interpretation of the circular dichroism spectrum of [6.6]vespirene. J. Am. Chem. Soc. 1977, 99, 6861−6869.
    連結：
83. 35. Edwards, L. O.; Simpson, W. T. Polarizations of Electronic Transitions from Azimuthal Variation in Fluorescence Intensity—with Application to Biphenyl. J. Am. Chem. Phys. 1970, 53, 4237−4240.
    連結：
84. 36. Ikeya, Y.; Taguchi, H.; Yosioka, I.; Kobayashi, H. The constituents of Schizandra chinensis Baill. I. isolation and structure determination of five new lignans, gomisin A, B, C, F and G, and the absolute structure of schizandrin. Chem. Pharm. Bull. 1979, 27, 1383-1394.
    連結：
85. 37. Buckleton, J. S.; Cambie, R. C.; Clark, G. R.; Craw, P. A.; Rickard, C. E. F.; Rutledge, P. S.; Woodgate, P. D. Oxidative coupling of lignans. II. non-phenolic coupling of diarylbutane lignans related to matairesinol dimethyl ether. Aust. J. Chem. 1988, 41, 305–324.
    連結：
86. 38. Borecka, B.; Cameron, S.; Linden, A.; Rashidi-Ranjbar, P., Sandström, J. X-ray crystallographic determination of absolute configurations and conformations of two conformational isomers of 1,2,3,4-dibenzo-trans-6,7-dibromo-1,3- cyclooctadiene, a 2,2'-bridged biphenyl. J. Am. Chem. Soc. 1990, 112, 1185−1190.
    連結：
87. 39. Blunder, M.; Pferschy-Wenzig, E. M.; Fabian, W. M. F.; Hüfner, A.; Kunert, O.; Saf, R.; Schühly, W.; Bauer, R. Derivatives of schisandrin with increased inhibitory potential on prostaglandin E and leukotriene B formation in vitro. Bioorg. Med. Chem. 2010, 18, 2809–2815.
    連結：
88. 40. Vorogushin, A.; Wulff, W. D.; Hansen, H.-J. Central-to-axial chirality transfer in the benzannulation reaction of optically pure fischer carbene complexes in the synthesis of allocolchicinoids. Tetrahedron 2008, 64, 949–968.
    連結：
89. 41. Mzaleyrat, J.-P., Wright, K., Gaucher, A., Toulemonde, N.; Wakselman, M.; Oancea, S.; Peggion, C.; Formaggio, F.; Setnička V.; Keiderling, T. A.; Toniolo, C. Induced axial chirality in the biphenyl core of the calpha-tetrasubstituted α-amino acid residue Bip and subsequent propagation of chirality in (Bip)n/Val oligopeptides. J. Am. Chem. Soc. 2004, 126, 12874–12879.
    連結：
90. 42. Liu, J.-S.; Li, L.; Yu, H.-G. Kadsulignan A and B, two novel lignans from Kadsura coccinea. Can. J. Chem. 1989, 67, 682–684.
    連結：
91. 43. Boyĕ, O.; Brossi, A.; Yen, H. J. C.; Hamel, E., Wegrazynski, B., Toome, V.. Natural products. Antitubulin effect of congeners of N-acetylcolchinyl methyl ether: synthesis of optically active 5-acetamidodeaminocolchinyl methyl ether and of demethoxy analogues of deaminocolchinyl methyl ether. Can. J. Chem. 1992, 70, 1237–1249.
    連結：
92. 44. Buckleton, J. S.; Cambie, R. C.; Clark, G. R.; Craw, P. A.; Rickard, C. E. F.; Rutledge, P. S.; Woodgate, P. D. Oxidative coupling of lignans. II. Non-phenolic coupling of diarylbutane lignans related to matairesinol dimethyl ether. Aust. J. Chem. 1988, 41, 305–324.
    連結：
93. 45. Billinsky, J.; Krol, E. S. Nordihydroguaiaretic acid autoxidation produces a schisandrin-like dibenzocyclooctadiene lignin. J. Nat. Prod. 2008, 71, 1612–1615.
    連結：
94. 46. Sagiv, J. Influence of substitution pattern on the benzenoid transitions: Quantitative evaluation of the electronic and vibrational components from new experimental polarization data. Tetrahedron 33, 1977, 2303–2313.
    連結：
95. 47. Ahmed, A. F.; Kuo, Y. H.; Dai, C. F.; Sheu, J. H. Oxygenated terpenoids from a formosan soft coral Sinularia gibberosa. J. Nat. Prod. 2005, 68, 1208−1212.
    連結：
96. 48. Heymann, H.; Tezuka, Y.; Kikuchi, T.; Supriyatna, S. Constituents of Sindora sumatrana MIQ. I. Constituents of Sindora sumatrana MIQ.I. Isolation and NMR spectral analysis of sesquiterpenes from the dried pods. Chem. Pharm. Bull. 1994, 42, 138−146.
    連結：
97. 49. Collado, I. G.; Hanson, J. R.; Macias-Sanchez, A. J. The oxidative coupling of coumaranone with disulfur dichloride. Tetrahedron 1996, 52, 7961−7972.
    連結：
98. 50. Kouno, I.; Yanagida, Y.; Shimono, S.; Shintomi, M.; Ito, Y.; Yang, C. S. Neolignans and a phenylpropanoid glucoside from Illicium difengpi. Phytochemistry 1993, 32, 1573−1577.
    連結：
99. 51. Baderschneider, B.; Winterhalter, P. Isolation and characterization of novel benzoates, cinnamates, flavonoids, and lignans from Riesling wine and screening for antioxidant activity. J. Agric. Food Chem. 2001, 49, 2788−2798.
    連結：
100. 52. Jiang, L.; Kojima, H.; Yamada, K.; Kobayashi, A.; Kubota, K. Isolation of some glycosides as aroma precursors in young leaves of Japanese pepper (Xanthoxylum piperitum DC.). J. Agric. Food. Chem. 2001, 49, 5888−5894.
     連結：
101. 53. Mshvildadze, V.; Legault, J.; Lavoie, S.; Gauthier, C.; Pichette, A. Anticancer diarylheptanoid glycosides from the inner bark of Betula papyrifera. Phytochemistry 2007, 68, 2531−2536.
     連結：
102. 54. Capasso, R.; Evidente, A.; Avolio, S.; Solla, F. A highly convenient synthesis of hydroxytyrosol and its recovery from agricultural waste waters. J. Agric. Food. Chem. 1999, 47, 1745−1748.
     連結：
103. 55. Li, R.; Weng, Z.; Pu, J.; Sun, H. Chemical Constituents from Schisandra sphenanthera. Chin. Chem. Lett. 2008, 19, 696−698.
     連結：
104. 56. Shao, X.; Bai, N. S.; He, K.; Ho, C. T.; Yang, C. S.; Sang, S. M. Apple polyphenols, phloretin and phloridzin: new trapping agents of reactive dicarbonyl species. Chem. Res. Toxicol. 2008, 21, 2042−2050.
     連結：
105. 57. Bilia, A. R.; Morelli, I.; Hamburger, M.; Hostettmann, K. Flavans and A-type proanthocyanidins from Prunus prostrata. Phytochemistry 1996, 43, 887−892.
     連結：
106. 58. Ibrahim, L. F.; El-Senousy, W. M.; Hawas, U. W. NMR spectral analysis of flavonoids from Chrysanthemum coronarium. Chem. Nat. Compd. 2007, 43, 659−662.
     連結：
107. 59. Caccamese, S.; Manna, L.; Scivoli, G.. Chiral HPLC separation and CD spectra of the C-2 diastereomers of naringin in grapefruit during maturation. Chirality 2003, 15, 661−667.
     連結：
108. 60. Sang, S. M.; Lapsley, K.; Jeong, W. S.; Lachance, P. A.; Ho, C. T.; Rosen, R. T. Antioxidative phenolic compounds isolated from almond skins (Prunus amygdalus Batsch). J. Agric. Food. Chem. 2002, 50, 2459−2463.
     連結：
109. 61. Kazuma, K.; Noda, N.; Suzuki, M. Malonylated flavonol glycosides from the petals of Clitoria ternatea. Phytochemistry 2003, 62, 229−237.
     連結：
110. 62. Kaouadji M. Further Acylated Kaempferol Rhamnosides from Platanus acerifolia Buds. J. Nat. Prod. 1993, 56, 1618−1621.
     連結：
111. 63. Taniguchi, M.; Yanai, M.; Xiao, Y. Y.; Kido, T.; Baba, K. Three isocoumarins from Coriandrum sativum. Phytochemistry 1996, 42, 843−846.
     連結：
112. 64. Yang, N. Y.; Tao, W. W.; Duan, J. A. Antithrombotic flavonoids from the faeces of Trogopterus xanthipes. Nat. Prod. Res. 2010, 24, 1843–1849.
     連結：
113. 65. Kanokmedhakul, S.; Kanokmedhakul, K.; Nambuddee, K.; Kongsaeree, P. New bioactive prenylflavonoids and dibenzocycloheptene derivative from roots of Dendrolobium lanceolatum. J. Nat. Prod. 2004, 67, 968−972.
     連結：
114. 66. Lin, R. J.; Cheng, M. J.; Huang, J. C.; Lo, W. L.; Yeh, Y. T.; Yen, C. M.; Lu, C. M.; Chen, C. Y. Cytotoxic compounds from the stems of Cinnamomum tenuifolium. J. Nat. Prod. 2009, 72, 1816−1824.
     連結：
115. 67. Subehan, S.; Kadota, S.; Tezuka, Y. In vitro mechanism-based inactivation of cytochrome P450 3A4 by a new constituent of Cinnamomum burmani. Planta Med. 2008, 74, 1474−1480.
     連結：
116. 第一部分
117. 3. Huang, T.C. (Ed.), 1996. Flora of Taiwan, second ed., vol. 2. Editorial Committee of the Flora of Taiwan, Taipei, pp. 481–483.
118. 41. Min, B. S.; Lee, S. Y.; Kim, J. H.; Lee, J. K.; Kim, T. J.; Kim, D. H.; Kim, Y. H.; Joung, H.; Lee, H. K.; Nakamura, N.; Miyashiro, H.; Hattori, M. Anti-complement activity of constituents from the stem-bark of Juglans mandshurica. Biol. Pharm. Bull. 2003, 26, 1042–1044.
119. 第二部分
120. 1. Liao, J. C. Lauraceae in Flora of Taiwan, 2nd ed.; Editorial Committee of the Flora of Taiwan: Taipei, 1996; Vol. 2, pp 443−483.
121. 2. Angmor, J. E.; Dicks, D. M.; Evans, W. C.; Santra, D. K. Studies on Cinnamomum zeylanicum. Planta Med. 1972, 21, 416−420.
122. 4. Macbeth, A. K.; Smith, G. E., West, T. F. β-Phellandrene. J. Chem. Soc., 1938, 119−123.
123. 28. Biscarini, P.; Bongini, A.; Casarini, D. Synthesis and characterization of chiral thioethers and mercury (II) halide complexes. Part 3.1.2 conformational energy calculation and NMR and CD spectra of the chiral isothiochroman (R)-(－)-4-ethel-3,4-dohydro-1H-2-benzothine. J. Chem. Res. 1990, 645−663.