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研究生:吳和澄
研究生(外文):Ho-Chen Wu
論文名稱:黃杞莖部化學及抗結核活性成分之研究
論文名稱(外文):Chemical Constituents and Antitubercular Activity from the Stem of Engelhardia roxburghiana
指導教授:陳益昇陳益昇引用關係
指導教授(外文):Ih-Sheng Chen
學位類別:碩士
校院名稱:高雄醫學大學
系所名稱:藥學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2011
畢業學年度:99
語文別:中文
論文頁數:219
中文關鍵詞:黃杞莖部抗結核活性
外文關鍵詞:Engelhardia roxburghianastemanti-TB
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黃杞 (Engelhardia roxburghiana Wall.) 屬於胡桃科 (Juglandaceae),為落葉性喬木,主要分佈於印度、印尼、中國大陸西南方及台灣中低海拔地區。
對近1300種台灣產之植物進行抗結核活性篩選,發現黃杞之根、莖及葉具抗結核活性。過去本研究室對黃杞之根部進行研究,共分離出11個新化合物及29個已知化合物,其中2-methoxyjuglone、3-methoxyjuglone、engelharquinone、engelhardione、及(–)-4-hydroxy-1-tetralone為具抗結核活性之化合物,而莖部進行活性篩選,發現其也具有抗結核菌活性。而黃杞莖部也同樣具有抗結核活性。
利用生物活性導向試驗,黃杞莖部乙酸乙酯層萃取物分離得到四個新diarylheptanoids:(–)-engelheptanoxide A (1)、engelheptanoxides B~D (2~4);兩個cyclic diarylheptanoids:engelhardiols A~B (5~6);一個naphthoquinone dimer:engelharquinonol (7);一個天然界首次分離之tetralone:(4S)-4,6-dihydroxy-1-tetralone (8)。以及24個已知化合物:squamolone (9)、rhoiptelol B (10)、methyl gallate (11)、(3R)-3'', 4''-epoxy-1-(4-hydroxyphenyl)-7-(3-methoxyphenyl)-
heptan-3-ol (12)、(2R)-3'', 4''-epoxy-2-hydroxy-1-(4-hydroxyphenyl)-7-(3-methoxyphenyl)-
heptan-3-one (13)、1-(4-hydroxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane-3,5-diol (14)、rhoiptelol C (15)、(–)-syringaresinol (16)、7-hydroxycadalene (17)、vomifoliol (18)、4-acetonyl-3,5-dimethoxy-p-quinol (19)、(+)-4-hydroxy-1-tetralone (20)、3-O-betulinic acid p-coumarate (21)、engelhardione (3'',4''-epoxy-1-(4-hydroxyphenyl)-7-(3-hydroxyphenyl)heptan-3-one) (44)、engeletin (47)、katuranin (51)、afzelin (57)、3-methoxyjuglone (63)、engelharquinone epoxide (65)、b-sitosterol (68)、b-sitosterone (70)、(–)-regiolone (74)、3-epi-betulinic acid (76) 及3-epi-betulinic acid acetate (77);已知化合物中, 9~21共13個化合物為自本植物首次分離。以上這些化合物之構造皆以光譜分析決定。另外對本植物莖部再次分離到之engelhardione (44)結構由3'',3''-epoxy-1-(4-hydroxyphenyl)- 7-(3-hydroxyphenyl)heptan-3-one改正成3'',4''-epoxy-1-(4-hydroxyphenyl)-7-(3-hydroxy- phenyl)heptan-3-one。
將以上化合物進行活性測試,(–)-engelheptanoxide A (1)、engelhardiol A (5)、engelhardiol B (6)、squamolone (9)、engelhadione (3'',4''-epoxy-1-(4-hydroxyphenyl)-7-(3-hydroxy-phenyl)heptan-3-one) (44)、katuranin (51)、3-methoxyjuglone (63) 及engelharquinone epoxide (65)皆顯示不錯的抗結核活性,其 MIC分別為 55.3、25.0、20.5、20.5、3.125、27.0、3.125及25.5 μg/mL。


Engelhardia roxburghiana Wall. (Juglandaceae) is a deciduous tree, distributed in India, Indochina, SW China, and low to middle altitudes of Taiwan. Approximately 1300 species of Formosan plants have been screened for antitubercular activity against Mycobacterium tuberculosis H37Rv in vitro, and E. roxburghiana was shown to be one of the active species. Previous investigations from our laboratory, eleven new compounds, and twenty-nine known compounds have been isolated from the root of this plant, among them, 2-methoxyjuglone, 3-methoxyjuglone, engelharquinone, engelhardione, and (–)-4-hydroxy-1-tetralone were antitubercular constituents. The stem of this plant also showed antitubercular activity.
Bioassay-guided fractionation of the active EtOAc-soluble layer of the stem has led to the isolation of 32 compounds, including four new diarylheptanoids: (–)-engelheptanoxide A (1), engelheptanoxides B~D (2~4); two new cyclic diarylheptanoids: engelhardiols A~B (5~6); one new naphthoquinone dimer: engelharquinonol (7), one first isolated from nature: (4S)-4,6-dihydroxy-1-tetralone (8); along with twenty-four known compounds, including squamolone (9), rhoiptelol B (10), methyl gallate (11), (3R)-3'', 4''-epoxy-1-(4-hydroxyphenyl)-7-(3-methoxy-
phenyl)heptan-3-ol (12), (2R)-3'', 4''-epoxy-2-hydroxy-1-(4-hydroxyphenyl)-7-(3-methoxy-phenyl)heptan-3-one (13), 1-(4-hydroxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane-3,5-diol (14), rhoiptelol C (15), (–)-syringaresinol (16), 7-hydroxycadalene (17), vomifoliol (18), 4-acetonyl-3,5-dimethoxy-p-quinol (19), (+)-4-hydroxy-1-tetralone (20), 3-O-betulinic acid p-coumarate (21), engelhardione (3'',4''-epoxy-1-(4-hydroxyphenyl)-7-(3-hydroxyphenyl)heptan-3-one) (44), engeletin (47), katuranin (51), afzelin (57), 3-methoxyjuglone (63), engelharquinone epoxide (65), b-sitosterol (68), b-sitosterone (70), (–)-regiolone (74), 3-epi-betulinic acid (76) and 3-epi-betulinic acid acetate (77). Among the isolated, thirteen compounds (9~21) were first isolated from this plant .The structures of these compounds were determined by spectroscopic analysis. We also revised the structure of engelhardione from 3'',3''-epoxy-1-(4-hydroxyphenyl)- 7-(3-hydroxyphenyl)heptan-3-
one to 3'',4''-epoxy-1-(4-hydroxyphenyl)-7-(3-hydroxy- phenyl)heptan-3-one.
Among the isolates, (–)-engelheptanoxide A (1), engelhardiol A (5), engelhardiol B (6), squamolone (9), engelhardione (3'',4''-epoxy-1-(4-hydroxyphenyl)-7-(3-hydroxyphenyl)heptan-3-one) (44), katuranin (51), 3-methoxyjuglone (63) and engelharquinone epoxide (65) showed antitubercular activity with MIC 55.3, 25.0, 20.5, 20.5, 3.125, 27.0, 3.125 and 25.5 μg/mL, respectively.


目錄 I~Ⅲ
圖目錄 Ⅳ~XI
表目錄 XII
中文摘要 XIII
英文摘要 XIV
Glossary of Abbreviations XV

第一章、序言 1
第二章、研究動機與目的 3
第三章、黃杞植物之考察 5
第四章、黃杞屬植物過去文獻回顧
第一節、過去化學成分之研究 8
第二節、過去藥理研究回顧 18
第五章、萃取與分離 19
第六章、化合物之結構鑑定
第一節、(–)-engelheptanoxide A (1) 24
第二節、engelheptanoxide B (2) 32
第三節、engelheptanoxide C (3) 39
第四節、engelheptanoxide D (4) 46
第五節、engelhardiol A (5) 53
第六節、engelhardiol B (6) 61
第七節、engelharquinonol (7) 69
第八節、(4S)-4,6-dihydroxy-1-tetralone (8) 80
第九節、squamolone (9) 84
第十節、rhoiptelol B (10) 89
第十一節、methyl gallate (11) 96
第十二節、(3R)-3'',4''-epoxy-1-(4-hydroxyphenyl)-7-(3-methoxyphenyl)-heptan-3-ol (12) 99
第十三節、(2R)-3'',4''-epoxy-2-hydroxy-1-(4-hydroxyphenyl)-7-(3-methoxy-methoxy-phenyl)heptan-3-one (13) 106
第十四節、(3S,5S)-1-(4-hydroxyphenyl)-7-(4-hydroxy-3-methoxy-phenyl)-heptane-3,5-diol (14) 110
第十五節、rhoiptelol C (15) 114
第十六節、(–)-syringaresinol (16) 118
第十七節、7-hydroxycadalene (17) 121
第十八節、vomifoliol (18) 127
第十九節、4-acetonyl-3,5-dimethoxy-p-quinol (19) 134
第二十節、(+)-4-hydroxy-1-tetralone (20) 137
第二十一節、3-O-betulinic acid p-coumarate (21) 140
第二十二節、3'',4''-epoxy-1-(4-hydroxyphenyl)-7-(3-hydroxyphenyl)heptan-3-one (44) 144
第二十三節、engeletin (47) 148
第二十四節、katuranin (51) 152
第二十五節、afzelin (57) 159
第二十六節、3-methoxyjuglone (63) 162
第二十七節、engelharquinone epoxide (65) 165
第二十八節、??-sitosterol (68) 169
第二十九節、??-sitosterone (70) 172
第三十節、(–)-regiolone (74) 175
第三十一節、3-epi-betulinic acid (76) 178
第三十二節、3-epi-betulinic acid acetate (77) 181
第七章、engelhardione 結構之改正 184
第八章、抗結核活性之研究 186
第九章、結論 188
第十章、實驗部分
第一節、儀器與材料 190
第二節、抗結核活性測試 192
第三節、黃杞莖部之萃取與分離 194
第四節、乙酸乙酯可溶部之分離 194
第五節、化合物之實驗數據 198
第十一章、參考文獻 215

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