仪花根、叶以及野八角果实化学成分的研究

【作者】 吴先富；

【导师】 庾石山； 石建功； 张东明；

【作者基本信息】 中国协和医科大学 ， 药物化学， 2009， 博士

【摘要】 仪花（Lysidicie rhodostegia）为豆科（Leguminosae）仪花属植物,产于我国广东、广西和云南等地。越南也有分布。本种根、茎、叶有小毒,能散瘀消肿,止血止痛。可治疗跌打损伤,骨折,风湿关节炎,外伤出血等症。前期本课题组从仪花根中分离得到多种结构类型的化合物,如间苯三酚类、二苯乙烯类、黄酮类、木脂素类等。其中,间苯三酚类化合物结构较为新颖,包括新骨架化合物。并且,大部分间苯三酚类化合物显示了一定的扩张血管或抗氧化的活性。利用LC-DAD、LC/ESI-MS、LC/ESI-MSⁿ和TLC等手段重点针对间苯三酚类化合物进行分离,从仪花根正丁醇部位以及再次采集的仪花根EtOAc部位中共分离得到9化合物,通过波谱和化学方法确定其结构为:仪花素I（W1）、仪花素J（W2）、仪花素K（W3）、（2S,3S,4S）-4-（3-异戊酰基-4-O-β-D-吡喃葡萄糖-2,6-二羟基苯基）-3,5,7,4′-四羟基黄烷（W4）、（2S,3S,4S）-4-（3-异戊酰基-4-O-β-D-吡喃葡萄糖-2,6-二羟基苯基）-3,5,7,3′,4′-五羟基黄烷（W5）、4-（3-异戊酰基-4-O-β-D-吡喃葡萄糖-2,6-二羟基苯基）-2,3-环氧-5,7,3′,4′-四羟基黄烷（W6）、间苯三酚1-异戊酰基-2-O-（6-O-没食子酰基）-β-D-吡喃葡萄糖苷（W7）、间苯三酚1-（2-甲基丁酰基）-2-O-β-D-吡喃葡萄糖苷（W8）和（E）-5,4′-二羟基二苯乙烯3-O-（6-O-没食子酰基）-β-D-吡喃葡萄糖苷（W9）。其中3个化合物（W1、W2和W3）为新骨架间苯三酚类衍生物,3个为天然产物中罕见的间苯三酚与黄烷3-醇的加合物（W4、W5和W6）,1个为新的间苯三酚糖苷类化合物（W7）,2个为首次从该属植物中分离得到的化合物（W8和W9）。同时,对3个新骨架化合物的生源途径进行了初步的推测和探讨。药理活性测试结果显示,化合物W1、W2和W3在高浓度(10^-4 M)时表现一定的抗氧化活性,化合物W4～W7在10^-4、10^-5和10^-6M浓度时均表现较强的抗氧化活性,其活性强于阳性对照维生素E。此外,利用计算CD谱法（TD-DFT）和Mo₂（OAc）₄衍生化CD谱法,确定了前期从仪花根中分离得到的新骨架化合物仪花素D、仪花素E和仪花素F的绝对构型,解决了其他方法不能解决的该类新骨架化合物手性碳绝对构型的问题。利用LC-DAD,LC-ESI-MSⁿ等技术对仪花叶的化学成分进行在线结构分析,根据已有的几类化合物的质谱裂解规律,推测了21个成分的结构,它们分别是:虎杖苷（A1）、白藜芦醇3-O-β-D-吡喃木糖苷（A2）、槲皮素7-O-β-D-吡喃葡萄糖苷（A3）、槲皮素7-O-α-L-吡喃鼠李糖苷（A4）、3,5,7,4′-四羟基黄酮3-O-α-L-吡喃鼠李糖苷（A5）、间苯三酚1-异戊酰基-2-O-α-L-吡喃鼠李糖-（1→6）-β-D-吡喃葡萄糖苷（B1）、仪花苷A（B2）、3,5,7,4′-四羟基黄酮3-O-β-D-吡喃葡萄糖苷（B4）、3,5,7,4′-四羟基-8-异戊烯基-4′-O-没食子酰基-黄烷-3-O-没食子酸酯（C1）、3,5,7,3′,4′-五羟基-黄烷-3-O-没食子酸酯（C2）、3,5,7,3′,4′,5′-六羟基黄酮3-O-α-L-吡喃鼠李糖苷（C3）、木樨草素7-O-α-L-吡喃鼠李糖苷（C5）、槲皮素7-O-（2-O-没食子酰基）-α-L-吡喃鼠李糖苷（C6）、槲皮素3-O-β-D-吡喃葡萄糖-（1→2）-β-D-吡喃葡萄糖苷（D1）、3,5,7,4′-四羟基黄酮3-O-β-D-吡喃葡萄糖-（1→2）-β-D-吡喃葡萄糖苷（D2）、3,5,7,3′,4′,5′-六羟基黄酮7-O-α-L-吡喃鼠李糖苷（D3）、槲皮素3-O-α-L-吡喃鼠李糖基-7-O-β-D-吡喃葡萄糖苷（E1）、槲皮素3-O-α-L-吡喃鼠李糖基-7-O-α-L-吡喃鼠李糖苷（E4）、3,5,7,4′-四羟基-3′-甲氧基-黄酮3-O-β-D-吡喃葡萄糖基-7-O-α-L-吡喃鼠李糖苷（E5）、槲皮素3-O-α-L-吡喃鼠李糖苷（E7）和3,5,7,4′-四羟基-黄酮3-O-α-L-吡喃鼠李糖基-7-O-α-L-吡喃鼠李糖苷（E8）。野八角（Iliicium simonsii Maxim）为木兰科八角属（Illicium L.）植物,产于我国贵州、四川和云南以及印度、缅甸。叶、果实入药,味辛,性热。具有镇呕、行气止痛、生肌接骨、灭虱杀虫之功效,可治胃寒作呕、膀胱疝气、胸前胀痛、疥疮等症。利用LC/UV并结合TLC显色重点针对野八角果实中植物醌（异戊烯基取代的C6-C3）类化合物进行分离,得到19个化合物,其中植物醌类化合物12个,包括3个新化合物（W10～W12）。利用波谱手段鉴定了这些化合物的结构,它们分别为:4-epi-illicinone E-12-shikimate（W10）、3-hydroxyillifunone B（W11）、7-hydroxy-2,3-dehydro-11-epi-illifunone C（W12）、illoliganone H（W13）、illoliganone G（W14）、2-烯丙基-2-（3-甲基-2-丁烯基）-4,5-亚甲二氧基-3,5-二烯-1-酮（W15）、illoliganone E（W16）、illoliganone A（W17）、illicinone E（W18）、illifunone C（W19）、illifunone D（W20）、2,3-dehydroillifunone C（W21）、dihydrodehydrodiconifenyl alcohol（W22）、trans-3-羟甲基-5-（3-羟基丙基）-7-甲氧基-2-（3,4,5-三甲氧基苯基）-2,3-二氢苯并[b]呋喃（W23）、styraxlignolide C（W24）、7R,7R′,8S,8S-（+）-neo-olivil-4-O-β-D-glucopyranosde（W25）、（1R,2S,5R,6S）-6-（3,4-dihydroxyphenyl）-2-（3,4-methylenedioxyphenyl）-3,7-dioxabicyclo[3,3,0]octane（W26）、（1R,2S,5R,6S）-6-（4-hydroxy-3-methoxyphenyl）-2-（3,4-dihydroxyphenyl）-3,7-dioxabicycio[3,3,0]octane（W27）和3,5,7-三羟基色原酮-3-O-β-D-吡喃木糖苷（W28）。更多还原

【Abstract】 Lysidice rhodostegia belongs to the genus Lysidice in the family Fabaceae.Lysidice rhodostegia is widely distributed in Guangdong,Guangxi,Yunnan of China,and its roots have been used for the the treatment of ache,fractures and hemorrhage by local folks in China.Phloroglucinols,stilbenes,Flavonoids,lignans and triterpenoids have been isolated from the this plant.Among these constituents,phloroglucinols are a type of compounds with novel structures and antivasoconstriction and antioxidant activities.Nine compounds were obtained from the erthanol extract of the roots of Lysidice rhodostegia.On the basis of chemical and spectra analysises,these compouns were elucidated as lysicidin A(W1),lysicidin B(W2),lysicidin C(W3),(2S,3S,4S)-4-(3-isovisovaleryl -4-O-β-D-glucopyranosyl-2,6-dihydroxypheny1)-3,5,7,4’-tetrahydroxyflavan (W4),(2S,3S,4S)-4-(3-isovaleryl-4-O-β-D-glucopyranosyl-2,6-dihydroxyphenyl)-3,5,7, 3’,4’-pentahydroxyflavan(WS),4-(3-isovaleryl-4-O-β-D-glucopyranosyl-2,6-dihydroxyphenyl) -2,3-epoxy-5,7,3’,4’-tetrahydroxyflavan(W6),phloroglucinol 1-isovaleryl-2-O-(6-O-galloyl)-β-D-glucopyranoside(W7),phloroglucinol 1-(2-methylbutyryl)-2-O-β-D-glucopyranoside (W8),(E)-5,4’-dihydroxystilbene 3-O-(6-O-galloyl)-β-D-glucopyranoside (W9).Among them,W1～W3 are novel compounds,W4～W6 are compounds with rare structures from natural products,W7 is a new compound and W8,W9 were isolated from the plants of this genus for the first time.Meanwhile,the plausible pathways for the biosynthesis of novel compounds W1～W3 were postulated.Antioxidant activities of the isolated compounds were investigated.Compounds W4～W7 exhibited obvious antioxidant effect at low,middle and high concentrations,which was stronger than those of the positive control agent vitamin E.In addition,the absolute configurations of novel compounds lysidicin D,lysidicin E and lysidicin F,which were isolated previously from the roots of Lysidice rhodostegia,were determined by a solid-state CD/TDDFT approach and dimolybdenum method.The compoents in fractions from the leaves of Lysidice rhodostegia were investigated by HPLC-DAD/ESI-MS~n.As a result,the possible structures of 21 constituents were deduced.Iliicium simonsii belongs to the genus Illicium in the family Magnoliaceae.This plant was distributed in Guizhou,Sichuan,Yunnan of China and India,Burma.Its leaves and fruits have been used as Chinese folk medicine for the treatment of vomiting,chest pain,Hernia and scabies.19 compounds were isolated from 95%alcohol extract of the fruits of the plant.Among them,W10～W12 are new compounds.On the basis of spectroscopic methods,their structures were determined as 4-epi-illicinone E-12-shikimate(W10),3-hydroxyillifunone B(W11),7-hydroxy-2,3-dehydro-11-epi-illifunone C(W12),illoliganone H(W13),illoliganone G(W14),2-allyl-2-(3-methylbutenyl) -4,5-methylenedioxycyclohexa-3,5-dien-1-one(W15),illoliganone E(W16),illoliganone A(W17),illicinone E(W18),illifunone C(W19),illifunone D(W20), 2,3-dehydroillifunone C(W21),dihydrodehydrodiconifenyl alcohol(W22),trans-3-(hydrpxymethyl) -5-(3-hydroxypropyl)-7-methoxy-2-(3,4,5-trimethoxyphenyl)-2,3-dihydrob enzo[b]furan(W23),styraxlignolide C(W24),7R,7R’,8S,8S-(+)-neo-olivil-4-O-β-D-glucopyranoside (W25),(1R,2S,5R,6S)-6-(3,4-dihydroxyphenyl)-2-(3,4-methylenedioxyphenyi) -3,7-dioxabicyclo[3,3,0]octane(W26),(1R,2S,5R,6S)-6-(4-hydroxy-3-methoxyphenyl) -2-(3,4-dihydroxxyphenyl)-3,7-dioxabicyclo[3,3,0]octane(W27),3,5,7-trihydroxylcchromone 3-O-β-D-xylpyranoside(W28).更多还原