【作者】 陈丽霞；

【导师】 邱峰；

【作者基本信息】 沈阳药科大学 ， 药物化学， 2006， 博士

【摘要】 常用中药穿心莲为爵床科穿心莲属植物穿心莲Andrographis paniculata(Burm．f．)Nees．的干燥地上部分。《中华人民共和国药典》(2000版)记载穿心莲：具有清热解毒，凉血消肿的功效。临床上主要用于风热感冒，咽喉肿痛，呼吸道感染，细菌性痢疾等疾病的治疗。利用现代色谱手段从穿心莲的干燥地上部分分离得到50个化合物，通过化学和光谱学方法鉴定了其中45个化合物的结构，它们分别是：穿心莲新苷(neo-andrographolide)(1)，3，14-二去氧穿心莲内酯(3，14-di-deoxyandrographolide)(2)，穿心莲内酯(andrographolide)(3)，14-去氧-11，12-二去氢穿心莲内酯(14-deoxy-11，12-didehydroandrographolide)(4)，19-hydroxy-8(17)，13-ent-labdadien-15，16-olide(5)，14-去氧穿心莲内酯(14-deoxy-andrographolide)(6)，3-oxo-14-deoxyandrographolide(7)，3-oxo-14-deoxy-11，12-didehydroandrographolide(8)~*，异穿心莲内酯(isoandrographolide)(9)，双穿心莲内酯A(bisandrographolide A)(10)，双穿心莲内酯B(bisandrographolide B)(11)，双穿心莲内酯C(bisandrographolide C)(12)，3α，19-dihydroxy-15-methoxy-8(17)，11，13-ent-labdatrien-16，15-olide(13)~*，14-去氧-17β-羟基穿心莲内酯(14-deoxy-17β-hydroxyandrographolide)(14)，18-羟基-14-去氧穿心莲内酯(18-hydroxy-14-deoxyandrographolide)(15)~*，(12R)-羟基穿心莲内酯((12R)-12-hydroxyandrographolide)(16)~*，(12S)-羟基穿心莲内酯((12S)-12-hydroxyandrographolide)(17)~*，14-去氧穿心莲内酯苷(14-deoxyandrographiside)(18)，14-去氧-11，12-二去氢穿心莲内酯苷(14-deoxy-11，12-didehydroandrographolide)(19)，穿心莲内酯苷(andrographiside)(20)，(7R)-羟基-14-去氧穿心莲内酯((7R)-7-hydroxy-14-deoxyandrographolide)(21)~*，(7S)-羟基-14-去氧穿心莲内酯((7S)-7-hydroxy-14-deoxyandrographolide)(22)~*，14-去羟基穿心莲内酯(14-dehydroxy-andrographolide)(23)~*，β-D-glucopyranosyl-8(17)，13-ent-labdadien-16，15-olid-19-oate(24)~*，8(17)，13-ent-labdadiene-15，16，19-triol(25)~*，3α，15，19-trihydroxy-8(17)，13-ent-labdadien-16-oic acid(26)~*，双穿心莲内酯E(bisandrographolide E)(27)~*，双穿心莲内酯F(bisandrographolide F)(28)~*，3α，19-dihydroxy-14，15，16-trinor-ent-labd-8(17)，11-diene-13-oic acid(29)~*，3α，12，19-trihydroxy-13，14，15，16-tetranor-ent-labd-8(17)-ene (30)，7，8-二甲氧基-5-羟基黄酮(7，8-dimethoxy-5-hydroxyflavone)(31)，5-羟基-7，8-二甲氧基二氢黄酮(5-dihydroxy-7，8-dimethoxyflavanone)(32)，5-羟基-7，8，2′，5′-四甲氧基黄酮(5-hydroxy-7，8，2′，5′-tetramethoxyflavone)(33)，5-羟基-7，8，2′-三甲氧基黄酮(5-hydroxy-7，8，2′-trimethoxyflavone)(34)，5-羟基-7，8，2′，3′-四甲氧基黄酮(5-hydroxy-7，8，2′，3′-tetramethoxyflavone)(35)，5，4′-二羟基-7，8，2′，3′-四甲氧基黄酮(5，4′-dihydroxy-7，8，2′，3′-tetramethoxyflavone)(36)，5，2′-二羟基-7，8-二甲氧基二氢黄酮(5，2′-dihydroxy-7，8-dimethoxynavanone)(37)，5，7，8-三甲氧基二氢黄酮(5，7，8-trimethoxyflavanone)(38)，5，2′-二羟基-7，8-二甲氧基黄酮(5，2′-dihydroxy-7，8-dimethoxyflavone)(39)，5，4′-二羟基-7-甲氧基-8β-D-吡喃葡萄糖苷(5，4′-dihydroxy-7-methoxy-8β-D-glucopyranosyloxyflavone)(40)，andrographidine C(41)，7，8，2′，5′-四甲氧基-5β-D-吡喃葡萄糖苷(7，8，2′，5′-tetramethoxy-5β-Dglucopyranosyloxyflavone)(42)，andrographidine A(43)，5，7，4′-三羟基黄酮(5，7，4′-trihydroxyflavone)(44)，5，7，3′，4′-四羟基黄酮(5，7，3′，4′-tetrahydroxyflavone)(45)。这45个化合物中，30个为二萜内酯类及二萜内酯衍生物类化合物，15个为黄酮类化合物。其中化合物8，13，15，16，17，21，22，23，24，25，26，27，28，29，30，42共16个化合物为新化合物，化合物7，36为两个新的天然产物，化合物5，38，44，45为首次从该属植物中分离得到。使用黑曲霉(Aspergillus niger，AS 3.739)对穿心莲中的主要二萜内酯类成分穿心莲新苷进行微生物转化研究，利用现代色谱手段从它的发酵液中共分离获得7种转化产物，通过化学和波谱学方法确定了其中5种转化产物的结构，分别是：8(17)，13-ent-labdadien-16，15-olid-19- oic acid(1)，3，14-二去氧穿心莲内酯(3，14-di-deoxyandrographolide)(2)，18-hydroxy-8(17)，13-ent-labdadien-16，15-olid-19-oic acid(3)，(3R)-hydroxy-8(17)，13-ent-labdadien-16，15-olid-19-oic acid (4)，(8S)，19-dihydroxy-ent-labd-13-en-16，15-olide(5)。这5个转化产物均为二萜内酯类化合物，其中转化产物3，4，5为新化合物。目前，有关穿心莲中化学成分抗病毒活性的研究报道较少，且多与目前的临床适应症无关。本文通过对中药穿心莲化学成分以及穿心莲新苷微生物转化的研究，分离鉴定多种化学成分，为阐明穿心莲抗病毒药效成分，以及探讨抗病毒构效关系的研究奠定基础。更多还原

【Abstract】 Chuanxinlian, the dried aerial parts of Andrographis paniculata (Burm.f.) Nees. is a Chinese herbal medicine used as an anti-inflammatory and antipyretic drug for treatment of fever, cold, laryngitis and diarrhea. And it was specified in the Pharmacopoeia of the P. R. China (2000) as an anti-virus and anti-bacterial remedy.The systematic investigation on chemical constituents led to the isolation of fifty compounds. On the basis of chemical evidences and spectral analysis, the structures of the 45 compounds were elucidated, and they are neoandrographolide (1), 3, 14-dideoxyandrographolide (2), andrographolide (3), 14-deoxy-11,12-didehydroandrographolide (4), 19-hydroxy-8(17), 13-ent-labdadien-15, 16-olide (5), 14-deoxy-andrographolide (6), 3-oxo-14-deoxyandrographolide (7), 3-oxo-14-deoxy-11, 12- didehydroandrographolide (8)*, isoandrographolide (9), bisandrographolide A (10), bisandrographolide B (11), bisandrographolide C (12), 3α, 19-dihydroxy-15-methoxy-8 (17), 11, 13-ent-labdatrien-16, 15-olide (13)*, (8S)-14-deoxy-17-hydroxyandrographolide (14), 18-hydroxy-14-deoxyandrographolide (15)*, (12R)-hydroxyandrographolide (16)*,(12S)-hydroxyandrographolide (17)*, 14-deoxyandrographiside (18), 14-deoxy-11, 12-didehydroandrographolide(19), andrographiside (20), (7R)-hydroxy-14-deoxyandrographolide (21)*, (7S)-hydroxy -14- deoxyandrographolide (22)*, 14-dehydroxy-andrographolide (23)*,β-D-glucopyranosyl- 8(17), 13-ent-labdadien-16, 15-olid-19-oate (24)*, 8(17), 13-ent-labdadiene-15, 16, 19-triol (25)*, 3α, 15, 19-trihydroxy-8(17), 13-ent-labdadien-16-oic acid (26)*, bisandrographolide E (27)*, bisandrographolide F (28)*, 3α, 19-dihydroxy-14, 15, 16-trinor-ent-labd-8(17), 11 -ene-13-oic acid (29)*, 3α, 12, 19-trihydroxy-13, 14, 15, 16-tetranor-ent-labd-8 (17)-ene (30)*, 7, 8-dimethoxy-5-hydroxyflavone (31), 5-dihydroxy-7, 8-dimethoxyflavanone (32), 5-hydroxy-7, 8, 2’, 5’-tetramethoxyflavone (33), 5-hydroxy-7, 8, 2’-trimethoxyflavone (34), 5-hydroxy-7, 8, 2’, 3’-tetramethoxyflavone (35), 5, 4’-dihydroxy-7, 8, 2’, 3’-tetramethoxyflavone (36), 5, 2’-dihydroxy-7, 8-dimethoxyflavanone (37), 5, 7, 8-trimethoxyflavanone(38), 5, 2’-dihydroxy-7, 8-dimethoxyflavone (39), 5, 4’-dihydroxy-7-methoxy-8β-D-glucopyranosyloxyflavone(40), andrographidineC (41), 7, 8, 2’, 5’-tetramethoxy-5β-D-glucopyranosyloxyflavone(42)~*, andrographidine A (43), 5, 7, 4’- trihydroxyflavone (44), 5, 7, 3’, 4’-tetrahydroxyflavone (45), respectively. Among these 45 compounds, 30 are diterpenoid lactones and derivates of them, 15 are flavones. Among them, 8, 13, 15, 16, 17, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 and 42 are 16 new compounds, 7 and 36 are two new naturally occurring products isolated from Andrographis paniculata, 5, 38, 44 and 45 were isolated for the first time from Andrographis genus.The microorganism Aspergillus niger, AS 3.739 was employed to bio-transform the substrate—neoandrographolide, seven products were isolated and purified from the fermented broth, and the structures of the five products were elucidated on the basis of chemical evidences and spectral analyses. The identified compounds are 8(17), 13-ent-labdadien-16, 15-olid-19-oic acid (1), 3, 14-di-deoxyandrographolide (2), 18-hydroxy-8(17), 13-ent-labdadien-16, 15-olid-19-oic acid (3)~*, (3R)-hydroxy-8(17), 13-ent-labdadien-16, 15-olid-19-oic acid (4)~*, (8S), 19-dihydroxy-ent-labd-13-en-16, 15-olide (5)~*, respectively. Among these five products of diterpenoid lactones, 3, 4, and 5 are new compounds.The above mentioned results would provide chemical substances for elucidating the antiviral constituents of Andrographis paniculata (Burm. f.) Nees., and further investigating antiviral structure-activity relationship.更多还原