Isatisine a, a novel alkaloid with an unprecedented skeleton from leaves of isatis indigotica

9 alpha,13 alpha-Dihydroxylisopropylidenylisatisine A (1), which was derived from isatisine A (2) and possessed an unprecedented fused pentacyclic skeleton, was isolated from the leaves of Isatis indigotica Fort. The structure and relative configuration w

Lycojapodine A, a Novel Alkaloid from Lycopodium japonicum

Lycojapodine A, a novel C16N-type Lycopodium alkaloid with an unprecedented 6/6/6/7 tetracyclic ring system, was isolated from the club moss Lycopodium japonicum. The structure and relative stereochemistry were elucidated on the basis of spectroscopic dat

Analysis of two trace alkaloid isomers in Strychnos nux-vomical by electrospray ionization tandem mass spectrometry

According to their molecular mass and ESI-MSn data, the trace alkaloid isomers pseudostrychnine and strychnine N-oxide in extracts of the total alkaloids from Strychnos nux-vomical were qualitatively analyzed by electrospray ionization tandem mass spectrometry (ESI-MSn) method after rough silica gel-column chromatographic separation. We also investigated the relationship between their fragmentation mechanism and structures of the two alkaloid isomers. A new method for quickly and highly sensitively analyzing the two alkaloid isomers was proposed.

Studies on the alkaloid components in Strychnos nux-vomical L. uncombined and combined with Glycyrrhiza Uralensis Fisch

The alkaloid components in Strychnos nux-vomical L. uncombined and combined with Glycyrrhiza uralensis Fisch have been investigated by electrospray ionization tandem mass spectrometry ( ESI-MSn) and HPLC. The experimental results demonstrated that the number of strychnine and brucine all declined in combined Strychnos nux-vomical L. with Glycyrrhiza uralensis Fisch, and the concentration level of strychnine fell obviously. The results of ESI-MS were identical to those of HPLC, which provided scientific basis for explanation of detoxicity of Glycyrrhiza uralensis Fisch and the reasonable combination of Strychnos nux-vomical L.

A New Method for Preparation and Characterization of Lipo-alkaloid

A simple route for the preparation of lipo-alkaloid is presented. When aconitine or one of its analogues is heated with a fatty acid for 20 min at 100degreesC in water, the C-8 acetyl group of aconitine is displaced by along chain fatty acyl group. The structures of the products were characterized by electrospray ionization tandem mass spectrometry.

五种毛壳霉属和曲霉属真菌代谢产物及细胞毒活性

毛壳霉属(Chaetomium)和曲霉属(Aspergillus)真菌产生多种具有生物活性的化合物。为系统阐明两属微生物的次生代谢物，对三种毛壳霉、两种曲霉真菌分别进行固态发酵，以色谱和波谱技术研究发酵物中的成分，分离鉴定了51个化合物，其中23个为新化合物，测试了部分化合物对肿瘤细胞的活性。 1、从螺卷毛壳霉（C. cochloides）固态发酵物中分离鉴定了11个化合物，3个新化合物为螺卷毛壳霉素A~C（1~3）。化合物1、3及dethio-tetra (methylthio) chetomin（4）对Bre-04、Lu-04和N-04细胞株生长抑制的GI50值为0.05~7.0 μg/mL。 2、从印度毛壳霉（C. indicum）固态发酵物中鉴定的三个异喹啉生物碱印度毛壳霉素A~C（12~14）代表两类骨架新颖的异喹啉生物碱。 3、从巴西毛壳霉（C. brasiliense）固态发酵物中鉴定了11个化合物，其中Mollicellins I~J（15~16）、2-Hydroxymethyl-6-methylmethyleugenin（19）为新化合物。化合物16和Mollicellin H（18）对Bre-04、Lu-04、N-04细胞株生长抑制的GI50值在2.5~8.6 μg/mL。 4、从土曲霉（A. terreus）固态发酵物中鉴定了18个化合物。5个为新化合物为Terretonin A~D（24~27）和Asterrelenin（28），24~27为二倍半萜化合物，28为吲哚生物碱。 5、从杂色曲霉(A. versicolor）固态发酵物中鉴定了16个化合物。9个新的化合物Brevianamides K~N (40~43)、Averins A~C (44~46)和Glyanphenines A~B (47~48)代表三种类型的生物碱。 6、综述了1997－2007年间新的二倍半萜的研究进展。 The fungi of the genera Chaetomium and Aspergillus produce various secondary metabolites with biological activities. In order to systematically study the secondary metabolites, the solid-state fermented rice culture of three species of Chaetomium and two of Aspergillus were chemically studied. By the means of chromatograhy and spectroscopy, 55 compounds were isolated and identified, among of them 23 were new ones. The biological activities of some compounds were investigated. 1. From the fungus C. cochliodes, three new epipolythiodioxopiperazines, chaetocochins A-C (1-3) were isolated, together with 8 known ones (4-11). Compounds 1, 3 and 4 showed growth inhibitory effects against cancer cell lines Bre-04, Lu-04 and N-04 with GI50 values from 0.05 to 7.0 μg/mL. 2. Three novel isoquinolines Chaetoindicins A-C (12-14) were isolated and identified from the fungus C. indicum. Chaetoindicin A, Chaetoindicins B-C represented two classes of novel carbon skeletons. 3. Three new compounds, Mollicellins I-J (15-16), and 2-hydroxymethyl-6-methylmethyleugenin (19), were isolated from C. brasiliense. Compound 16 and Mollicellin H (18) showed growth inhibitory effects against cancer cell lines Bre-04, Lu-04 and N-04 with GI50 values from 2.5 to 8.6 μg/mL. 4. Eighteen compounds were isolated from the fungus A. terreus. Terretonin A-D（24 - 27）and Asterrelenin（28） are new compounds belonging to sesterterpoids and indole-ralated alkaloid, respectively. 5. From the fungus A. versicolor, sixteen secondary metabolites, including nine new ones, Brevianamides K-N (40-43), Averins A-C (44-46), and Glyanphenines A-B (47-48), were isolated and identified. Brevianamides K-N (40-43), Averins A-C (44-46), and Glyanphenines A-B (47-48) represented three classes of alkaloids. 6. New sesterterpenes and their bioactivities reported from 1997 to 2007 were summarized.

四种药用植物的化学成分及芍药苷的微生物转化研究

本学位论文共有5章。第一章报道白芍的化学成分及芍药苷的微生物转化研究成果；第二章报道天山雪莲的化学成分研究；第三章报道两面针的化学成分研究；第四章报道通关藤的化学成分研究成果；第五章概述了花椒属植物中最近十年报道的新化合物及药理研究情况。 在第1章的第一部分报道了白芍（Paeonia lactiflora Pall.）的化学成分。我们采用正、反相硅胶柱层析等各种分离方法，从白芍的干燥根中共分离出14个化合物，其中1个为新化合物，其结构通过波谱分析证实为没食子酰白芍苷，另外还有2个为首次从该植物中分离得到。第二部分报道了芍药苷的微生物转化生产芍药苷代谢素-I的研究，从15株厌氧菌中筛选出10株有转化活性的菌株，其中短乳杆菌Lactobacillus brevis AS1.12的转化活性最好，对其转化条件进行了初步的筛选，确定了相对合理的转化工艺。 在第2章报道了天山雪莲（Saussurea involucrate Kar.et Kir.）全草乙醇提取物化学成分的分离纯化和结构鉴定。通过正、反相硅胶柱层析等分离纯化和MS、NMR等波谱解析，共分离鉴定了28个化合物，结构类型分属于黄酮、倍半萜和木脂素等，其中2个新倍半萜化合物的结构分别表征为6α-羟基云木香酸6-β-D-吡喃葡萄糖苷和11βH-11,13-二氢去氢云木香内酯8α-O-(6′-乙酰)-β-D-吡喃葡萄糖苷。 第3章报道了两面针（Zanthoxylum nitidum （Roxb.）DC.）干燥根的乙醇提取物化学成分的分离纯化和结构鉴定。通过正、反相硅胶柱层析等分离纯化和MS、NMR等波谱解析以及X-射线单晶衍射，共分离鉴定了16个生物碱，结构类型分属于苯并啡啶类、喹啉类和阿朴啡类等，其中2个新苯并啡啶类生物碱的结构分别表征为二聚双氢两面针碱和丙酮基双氢崖定椒碱。 第4章报道了通关藤（Marsdenia tenacissima (Roxb.) Wight et Arn.）水提取物化学成分的分离纯化和结构鉴定。通过正、反相硅胶柱层析等分离纯化和MS、NMR等波谱解析以及X-射线单晶衍射，共分离鉴定了14个化合物，结构类型均属于C21多羟基甾醇，其中4个新化合物tenacigenoside A, tenacigenoside B, tenacigenoside C和tenacigenoside D的结构分别表征为3-O-6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→4)-β-D-oleandropyranosyl-17β-tenacigenin B (62), 3-O-2,6- dideoxy-4-O-methyl-D-lyxo-hexopyranosly-11α-O- methylbutyryl-12β-O-acetyl-tenacigenin B (63), 3-O-6-deoxy-3-O-methyl-β-D- allopyranosyl-(1→4)-β-D-oleandropyranosyl-11α-O-tigloyl-tenacigenin C (64)和3-O-6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→4)-β-D-oleandropyranosyl-11α-O-2- methylbutyryl-tenacigenin C (65)。 第5章概述了花椒属植物的化学成分及药理活性研究进展。 This dissertation consists of 5 chapters. The first chapter elaborate the phytochemical investigation of Paeonia lactiflora Pall., and microbial transformation of paeoniforin. The second, third and four chapters elaborate the phytochemical investigation of Saussurea involucrate Kar.et Kir., Zanthoxylum nitidum (Roxb.) DC. and Marsdenia tenacissima (Roxb.) Wight et Arn., respectively. Chapter 5 is a review on chemical constituents and bioactivities of Zanthoxylum species. The part one of chapter 1 focus on the isolation and identification of chemical constituents from P. lactiflora. Fourteen compounds were isolated from the roots of P. lactiflora by repeat column chromatography over normal and reversed phase silica gel. Among them, one is a new compound and the structure was suggested as galloyl-albiflorin by spectral evidence. In addition, two compounds were firstly reported in this plant. The part 2 is about microbial transformation of paeoniforin. Chapters 2, 3 and 4 were isolations and identifications of chemical constituents from S. involucrate, Z. nitidum and M. tenacissima, respectively. From the aerial parts of S. involucrate, 28 compounds including 7 flavonoids and 13 sesquiterpenoids were isolated and identified. Among them, 2 new compounds were characterized as 6α-hydroxycostic acid 6-β-D-glucoside and 11βH-11,13-dihydrodehydro- costuslactone 8α-O-(6'-acetyl)-β-D-glucoside, respectively, by means of spectroscopic analysis. Otherwise, 11 ones were firstly reported from this plant. The third chapter is about the phytochemical investigation of Z. nitidum. Sixteen compounds were isolated and identified. Among them, 2 new benzophenanthridine alkaloids were characterized as 8-acetonyldihydrofagaridine and 1,3-bis(8-dihydronitidinyl)-acetone by spectroscopic analysis. The fourth chapter is about the phytochemical investigation of M. tenacissima. Fourteen compounds were isolated and identified. Among them, 4 new compounds, tenacigenosides A~D, were characterized as 3-O-6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→4)-β-D-oleandropyranosyl-17β- tenacigenin B, 3-O-2,6-dideoxy-4-O-methyl-D-lyxo-hexopyranosly-11α-O-methyl butyryl-12β-O-acetyl-tenacigenin B, 3-O-6-deoxy-3-O-methyl-β-D-allopyranosyl- (1→4)-β-D-oleandropyranosyl-11α-O-tigloyl-tenacigenin C, and 3-O-6-deoxy-3-O- methyl-β-D-allopyranosyl-(1→4)-β-D-oleandropyranosyl-11α-O-2-methylbutyryl- tenacigenin C. Chapter 5 is a review on recent progress in bioactive constituents from plants of Zanthoxylum species.

五枫藤、小驳骨和川西茶藨的化学成分研究

八月瓜属植物五枫藤(Holboellia latifolia Wall.)和驳骨草属植物小驳骨(Gendarussa vulgaris Nees)均为药用植物, 前者化学成分研究不深入, 后者的化学成分未见报道。川西茶藨(Ribes takare D. Don)为茶藨子属植物, 没有化学成分的报道。本论文对三个植物的化学成分和活性成分进行了研究, 主要通过色谱方法分离得到了48 个化合物, 采用波谱分析或与已知标准品对照等手段鉴定了它们的结构, 其中有1 个新的原小檗碱类化合物和3 个新的联苯类化合物,发现了具有细胞毒活性和α-葡萄糖苷酶抑制活性的化合物。1、从五枫藤地上部分的95%乙醇提取物中分离得到了12 个化合物: 五加苷K (1)、hederagenin 3-O- α-L-rhamnopyranosyl-(1→2)- α-L-arabinopyranoside (2)、β-萘乙酸(3) 、3-O-α-L-rhamnopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→3)]-α-L-arabinopyranosyl oleanolic acid 28-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl ester (4) 、3-O- α-L-rhamnopyranosyl-(1→2)-O- β- D-glucopyranosyl-(1→2)- α-L-arabinopyranosyl oleanolic acid (5) 、3-O-( β-D-glucopyranosiduronic acid)-oleanolic acid 28-O- β-D-glucopyranoside (6)、lup-20(29)-en-3-one (7)、lupeol (8)、β-谷甾醇(9)、齐墩果酸(10)、乌苏酸(11)、β-胡萝卜苷(12)。化合物1 对Lu-06、N-04 和Bre-04 癌细胞株的GI50 分别是0.77µg/mL、1.26 µg/mL 和1.55 µg/mL, 化合物2 对N-04 癌细胞株的GI50 为2.44 µg/mL。2、从小驳骨地上部分的95%乙醇提取物中分离得到了1 个原小檗碱类新化合物13-hydroxyl gusanlung A (25), β-谷甾醇(9)、齐敦果酸(10)、β-胡萝卜苷(12)、棕榈酸(1-)甘油酯(13)、棕榈酸(14)、阿苯哒唑(15)、阿苯哒唑砜(16)、阿苯哒唑亚砜(17)、aurantiamide acetate (18)、华良姜素(19)、芫花素(20)、(-)-丁香树酯醇(21)、gusanlung B (22) 、eupteleasaponinsⅤ acetate (23)、gusanlungA (24)、刺五加苷E (26)、岩白菜素(27)、咖啡酸(28)。化合物25 对肝癌细胞株(HepG2) 的GI50 为2.08 µg/mL。3、从川西茶藨地上部分的95%乙醇提取物中分离鉴定了22 个化合物: β-谷甾醇(9) 、β- 胡萝卜苷(12) 、O-acetyloleanolic aldehyde (29),4,7,8-trimethoxy-2,3-methylenedioxydibenzofuran (30) 、3', 5-dimethoxy-3, 4-methylenedioxybiphenyl (31) 、桦木醇(32) 、6,7-dimethoxy-1-methyl-3,4-dihydroquinolin-2-one (33)、3'-hydroxy-5-methoxy-3,4-methylenedioxybiphenyl (34) 、7-hydroxy-4,8-dimethoxy-2,3-methylenedioxydibenzofuran (35)、桦木醛(36)、没食子酸(37) 、6β- 羟基-4- 烯-3- 酮- 豆甾醇(38) 、5α, 8α-epidioxy-(22E,24R)-ergosta-6, 22-dien-3β-ol (39)、verrucofortine (40)、6-methoxycalpogoniumisoflavone A (41)、2-羟基二苯甲酮(42)、桦木酸(43), 3, 5-二甲氧基苯甲酸-4-O-β-D-吡喃葡萄糖苷(44)、洋芹素(45)、刺槐素(46)、水杨酸(47)、洋芹素-5-O- β-D-葡萄糖苷(48), 化合物30、31 和35 为新的联苯化合物。化合物30的α-葡萄糖苷酶抑制率为10.2% (1.00 mg/mL); 化合物35 的抑制率为17.2% (1.00mg/mL)。4、综述了1960 年以来原小檗碱类化合物药理活性研究进展。 Plants Holboellia latifolia Wall and Gendarussa vulgaris Nees, are used as folkmedicine. Ribes takare D. Don belongs to the genus Ribes. The three plants have notbeen chemically studied in detail. Chemical and bioactive study of three plants led tothe isolation of 48 compounds by chromatography. Their structures were elucidatedon the basis of spectroscopic evidence or comparison with authentic samples. Amongthe 48 componds isolated one protoberberine alkaloid and three biphenyls are newones. Cytotoxic and α-glucosidase inhibitory compounds had been found.1. Twelve compounds were isolated from the 95% ethanol extract of the aerial partof H. latifolia Wall. They were characterized as fellow: eleutheroside K (1),hederagenin-3-O- α-L-rhamnopyranosyl-(1→2)- α-L-arabinopyranoside (2),2-naphthyl acetic acid (3),3-O-α-L-rhamnopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→3)]-α-L-arabinopyranosyl oleanolic acid 28-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl ester (4), 3-O- α-L-rhamnopyranosyl-(1→2)-O- β- D-glucopyranosyl-(1→2)- α-L-arabinopyranosyl oleanolic acid (5),3-O-( β-D-glucopyranosiduronic acid)-oleanolic acid-28-O- β-D-glucopyranoside (6),lup-20(29)-en-3-one (7), lupeol (8), β-sitosterol (9), oleanolic acid (10), ursolicacid (11), and β-daucosterol (12). Compound 1 showed moderate cytotoxicity againstLu-06 (GI50, 0.77 µg/mL), N-04 (GI50, 1.26 µg/mL) and Bre0-4 (GI50=1.55 µg/mL)and compound 2 showed moderate cytotoxicity against N-04 (GI50=2.44 µg/mL).2. A new protoberberine alkaloid, 13-hydroxyl gusanlung A (25), was isolated fromthe aerial part of Gendarussa vulgaris Nees, together with β-sitosterol (9), oleanolicacid (10), β-daucosterol (12), glycerol monopalmitate (13), palmific acid (14),albendazole (15), albendazole sulphone (16), albendazole sufloxide (17), aurantiamideacetate (18), kumatakenin (19), genkwanin (20), (-)-syringaresinol (21), gusanlung B(22), eupteleasaponinsⅤ acetate (23), gusanlung A (24), eleutheroside E (26),bergenin (27) and caffeic acid (28). Compound 25 showed cytotoxicity against HepG2 cells (GI50, 2.08 µg/mL).3. Phytochemical study of the Ribes takare D. Don led to the isolation of three newbiphenyls, 4,7,8-trimethoxy-2,3-methylenedioxydibenzofuran (30), 3', 5-dimethoxy-3,4-methylenedioxybiphenyl (31) and 7-hydroxy-4,8-dimethoxy-2,3-methylenedioxydibenzofuran (35), along with nineteenknown compounds, β-sitosterol (9), β-daucosterol (12), O-acetyloleanolic aldehyde(29), betulin (32), 6,7-dimethoxy-1-methyl-3,4-dihydroquinolin-2-one (33),3'-hydroxy-5-methoxy-3, 4-methylenedioxybiphenyl (34), betulinic aldehyde (36),gallic acid (37), stigmast-4-en-6β-ol-3-one (38), 5α, 8α-epidioxy-(22E, 24R)-ergosta-6,22-dien-3β-ol (39), verrucofortine (40), 6-methoxycalpogonium isoflavone A (41),2-hydroxybenzophenone (42), betulinic acid (43), 3,5-dimethoxygallic acid-4-O- β-D-glucopryranoside (44), apigenin (45), acacetin (46), salicylic acid (47) andapigenin-5-O- β-D-glucopryranoside (48). α-Glucosidase inhibitory rates ofcompound 30 and 35 were respectively 10.2% and 17.2% at a concentration of 1.00 mg/mL).4. Pharmacological activities of protoberberines were summarized.

二萜生物碱植物的化学成分研究

本论文由三个部分组成。第一部分是综述性文章-天然C19-二萜生物碱的结构及其核磁共振波谱。这篇综述参考160余篇文献，将迄今为止发表的230余个天然C19-二萜生物碱按其结构和波谱特征，分为10个类型。重点叙述了每个类型的结构和核磁共振波谱，对一些立体构型与13C-NMR化学位移的关系进行了讨论。最后以表格的形式报导了每个天然C19-二萜生物碱的结构及其植物来源，并把其中170余个收集到的13C-NMR化学位移数据整理成表，作为手册，对鉴定此类化合物大有帮助。第二部分是实验论文--弯啄乌头的化学成分研究。重点报导了弯啄乌头(Aconitum campylorrhynchun Hand-Nazz.)中分离到的一个新生物碱--8-乙酰都啦碱(8-acetyldolaconine)的结构鉴定，并根据DEPT、COSY、COLO等对1H-NMR和13C-NMR的所有信号归属都进行了指定。通过各种图谱还发现这个生物碱的A环同时存在着椅式和船式两种构象导购体。另外还报导了从同一植物的生物碱部分分离到的两个二萜生物碱，它们都是嘟啦碱和aconosine.在非生物碱部分还分离到三个化合物，经鉴定证明是β-谷甾醇、棕榈酸和香豆酸。第三部分也是实验论文--展毛翠雀花中生物碱成分的研究。报导了从展毛翠雀花(Delphinium Kamaonense Var.glabrescens W. T. Wang)中初步分离到的两个生物碱。经IR、NS、1H-NMR和13C-NMR等方法确定结构，证明其中一个是新化合物，命名为展毛翠雀碱(glabredelphinine)。另外一个是前几年发现的二萜生物碱tatsiensine。这两个化合物的A环上都有碳-碳不饱和键，这在天然C19-二萜生物碱中还比较少见。This master's thesis consists of three parts. The first part is a review: The relationship between the chemical structures of natural C19-diterpene alkaloids and their NMR chemical shift data. The C19-diterpene alkaloids were divided into ten types according to their structures and NMR data. Some relationaships between configuration and NMR chemical shift have been discussed. The structures and distributions of more than 230 known C19-diterpene alkaloids and the assignments of 13C-NMR data of the 170 alkaloids of them were listed in tables. The second part is an experimental paper, Studies on the chemical constituents of Aconitum campylorrhynchum. Six compounds were isolated from the roots of title plant. One of them is a new alkaloid. It has been elucidaled as 8-acetyldolaconine by means of IR, MS, 1H-NMR,13C-NMR,DEPT,COSY,COLOC and on the basis of identification with aconosine by saponification. Other five compounds were idenfified as dolaconine, aconosine,β-sitosterol, palmitic acid and p-coumaric acid. The third part is also experimental paper: The alkaloids of Delphinium Kamaonense var.glabrescens. Two alkaloids were isolated from the roots of title plant. One of them, C22H22O6N,m.p.201-3℃,named glabredelphinine, was proved to be a new compound. Its structure has been established as 2(3)-dehydro-6-demethyl-18-delcosine by means of IR, MS, 1H-NMR and 13C-NMR.The other one was identified as tatsiensine by comparising of IR, MS, 1H-NMR and 13C-NMR data with that from the literatute.

三种藏药材的化学成分研究

本学位论文报道了西藏产三种藏族传统植物药材的化学成分研究。论文由四章组成，前三章是实验部分，分别报道了尼泊尔黄堇(Corydalis hendersonii Hemsl.)、藏波罗花(Incarvillea younghusbandii Sprague)和全缘叶绿绒蒿(Meconopsis interifolia Franch.)的化学成分研究结果。从这三种青藏高原药用植物中共分离鉴定出33 个化合物，其中1 个是新化合物。第四章概述了罂粟科紫堇属植物的化学和药理研究进展。 第一章为尼泊尔黄堇的化学成分研究。通过正、反相硅胶柱色谱等分离方法从药用植物尼泊尔黄堇的地上部分共分离纯化得到12 个化合物。运用MS、1H-NMR、13C-NMR、DEPT、HMBC、NOESY 等现代波谱学方法将它们的结构鉴定为：刺罂粟碱(1) ， 普托品(2) ， 新那亭(3) ， 斯可任(4) ， tetrahydrothalifendine (5) ，9-methyl-decumbenine C (6)，tetrahydroberberrubine (7)，隐品碱(8)，α-别隐品碱(9)，6,7-methylenedioxy-1(2H)-oxoisoquinolinone (10)，6-丙酮基-5,6 -二氢血根碱(11)和β-谷甾醇(12)。其中化合物6 为新化合物，为首次发现的分子骨架上C-9 位连有甲基的苯肽异喹啉类型生物碱。另外，除化合物1 和2 外，其它9 个生物碱（3～11）均为首次从该种植物中分离得到。同时，我们还对对尼泊尔黄堇中的总生物碱进行了串联质谱分析。 第二章为藏波罗花的化学成分研究。从该药用植物的地上部分共分离得到16个化合物，通过理化常数和波谱数据鉴定为：异佛手柑内酯(1)，6-甲氧基当归素(2)，欧前胡素(3)，花椒毒内酯(4)，珊瑚菜素(5)，水合氧化前胡素(6)，rivulobirin A (7)，齐墩果酸甲酯(8)，咖啡酸甲酯(9)，银桦酸(10)，(D)-boschniakinic acid (11)，对羟基苯甲酸(12) ， tert-O-β-D-glucopyranosyl-(R)-heraclenol (13) ， 5-methoxy-8-O-β-D-glucopyranosyloxypsoralen (14)，前胡苷V(15)和苯乙醇-O-β-D-吡喃葡萄糖-(1→2)-O-β-D-吡喃葡萄糖苷(16)。所有以上化合物均为首次从该种植物中分离得到。另外我们还首次对藏波罗花挥发油的化学成分进行了气相色谱-质谱(GC-MS)联用分析，共鉴定出39 个挥发性成分。 第三章为全缘叶绿绒蒿化学成分的分离鉴定。从传统藏药材全缘叶绿绒蒿地上部分共分离纯化出8 个化合物。通过理化常数和波谱数据将他们的结构分别鉴定为：去甲血根碱(1)，β-谷甾醇(2)，3-羟基-齐墩果烷-12(13)-烯-30-酸(3)，6-丙酮基-5,6-二氢血根碱(4)，木犀草素(5)，胡萝卜苷(6)，quercetin 3-O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside (7)和普托品(8)。其中化合物1，4 和7 为首次从该种药用植物中分离得到。 第四章为综述，总结和归纳了近年来罂粟科紫堇属植物的化学和药理研究进展。 This dissertation consists of four parts. The first, second and third parts report the studies on the chemical constituents from the medicinal plants of Corydalis hendersonii, Incarvillea younghusbandii and Meconopsis interifolia. The forth part reviews the progress of the studies on Corydalis species. The first chapter is about the isolations and identifications of alkalids from the aerial parts of C. hendersonii which is a traditional Tibetan medicine to treat febrifuge, high blood pressure and hepatitis. A new isoquinoline alkaloid, 9-methyl-decumbenine C (6), together with ten known alkaloids, stylopine (1), protopine (2), canadine (3), scoulerine (4), tetrahydrothalifendine (5), tetrahydroberberrubine (7), cryptopine (8), α-allocryptopine (9), 6,7-methylenedioxy-1(2H)-isoquinolinone (10) and 6-acetonyl-5,6-dihydrosanguinarine (11), and β-sitosterol (12) were isolated. Their structures were elucidated by spectroscopic methods. Furthermore, the total alkaloids were analyzed by ESI-MSn. The second chapter is about the isolations and identifications of chemical constituents from the aerial parts of I. younghusbandii. Sixteen compounds were isolated and purified by normal and reversed phase silica gel column chromatography. By spectral analysis, there structures were identified as isobergapten (1), sphondin (2), imperatorin (3), xanthotoxin (4), phellopterin (5), heraclenol (6), rivulobirin A (7), methyl oleanolate (8), methyl caffeate (9), grevillic acid (10), (D)-boschniakinic acid (11), 4-hydroxybenzoic acid (12), tert-O-β-D-glucopyranosyl-(R)-heraclenol (13), 5-methoxy-8-O-β-D-glucopyranosyloxypsoralen (14), decuroside Ⅴ(15), and phenylethyl-O-β-Dglucopyranosyl-(1→2)-β-D-glucopyranoside (16). All of these compounds were isolated from this plant for the first time．By the way, the chemical components of the essential oil from I. younghusbandii were analyzed by GC-MS for the first time. The third chapter is about the the isolations and identifications of the chemical constituents of M. interifolia. Eight compounds were isolated and identified as norsanguinarine (1), β-sitosterol (2), 3-hydroxyolean-12(13)-en-30-oic acid (3), 6-acetonyl-5,6-dihydrosanguinarine (4), luteolin (5), daucosterol (6), quercetin 3-O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside (7) and protopine (8). The compounds 1, 4 and 7 were isolated from this herb for the first time. The last chapter is a review of the research progress of the studies on Corydalis species, which includes the chemical constituents in this genus and their pharmacology.

吲哚生物碱Desbromoarborescidine A 的全合成及烯胺C-亚磺酰化反应研究

从新几内亚核桃木的树皮中分离得到的吲哚类喹诺里西定生物碱10-Desbromoarborescidine A，因发现其具有阻滞钙离子通道的活性而倍受关注。10-Desbromoarborescidine A由A、B、C、D四个环组成，只有一个手性中心，是吲哚生物碱中结构较简单的一种，常作为此类生物碱全合成方法的模型化合物。但迄今为止，能高效而简便的实现手性10-Desbromoarborescidine A不对称全合成方法线路不多，大多数以不对称诱导的方式建立其手性中心，手性催化的方式仅有一例金属催化。从逆合成分析可知，Desbromoarborescidine A的全合成可以通过亚胺不对称催化还原进行关键的手性中心构建，而本课题组在之前的研究中通过手性有机小分子催化剂的发展，已将三氯硅烷氢转移还原亚胺发展成了一类简便实用、高效、高对映选择性并具有优良底物适应范围的不对称催化反应，我们希望以这一反应作为关键手段，发展一条Desbromoarborescidine A及其类似物不对称合成新路线。 根据我们设计的新路线，首先成功合成了其关键中间体，然后我们进行了关键的不对称催化尝试。用本实验室已有的高性能有机小分子催化剂虽得到了较好的对应选择性，但是产率很低。同时，为了验证整条线路的可行性，我们也用消旋的中间体进行拉通线路的尝试。但不幸的是，在脱除保护基时遇到了很大困难。尝试换不同的保护基，或改变脱保护基的顺序，都未能成功合成目标产物。究其原因可能是由于吲哚的特殊性造成的，吲哚类亚胺与常规的芳香亚胺有较大的差异，其NH基团无论保护还是不保护，对与其2位相联接的C=N双键均有很大的影响，导致其不对称催化还原难以进行。另外，由于所设计的还原产物含有处在吲哚苄位的胺基，稳定性较差，造成保护基脱除困难。 烯胺C-亚磺酰化反应是本课题组最近发现的一个新反应，之前未见文献报道。本研究对该反应进行了反应条件优化和底物扩展，发现带Cbz，Ac，COt-Bu，CO2Et，Bz等保护基的一系列环状和非环状烯胺在亚磺酸钠、DMAc和MeSiCl3的共同作用下能高效高产率生成β-胺基烯基亚砜类新化合物，为合成多官能团化的烯基亚砜新化合物提供了一条简便实用的途径。 The main constituent of Dracontomelum mangiferum B1, indoloquinolizidine alkaloid 10-Desbromoarborescidine A, has drawn great attention due to its calcium channel blocking activity. Its molecular structure is relatively simple compared with the other alkaloids of the same type, which has only one chiral center, albeit with four cycles A, B, C, and D. This compound is often used as a model target for exploring different strategies for the total synthesis of indole alkaloids. Nevertheless, so far there still lack practical and highly efficient methods for the asymmetric total synthesis of 10-Desbromoarborescidine A. Most of the current available methods rely on stoichiometric asymmetric synthesis for the construction of the chiral center. There is only one example reporting utilization of asymmetric catalysis, but with transition metal complex as the catalyst. Our retrosynthetic analysis shows that catalytic asymmetric reduction of imine could be used as the key step for the construction of the chiral center of Desbromoarborescidine A. Since in the previous studies our group has developed the asymmetric reduction of imines by trichlorosilane into a practical and highly efficient and enantioselective method using newly designed chiral organocatalysts, we hope to apply this method to develop a novel synthetic route for the total synthesis of Desbromoarborescidine A and its analogues in this study. According to the newly designed synthetic route, we first accomplished the synthesis of the key intermediates which was then examined for the critical asymmetric catalysis. The asymmetric reduction using the highly efficient organocatalysts, developed in our lab afforded high ee but poor yield. We tried different reaction conditions to improve the yield, but failed to get any good results. Simultaneously, to vertify the feasibility of the synthetic route we designed, we also tired to go through the route toward the racemic synthesis of Desbromoarborescidine A. But unfortunately, protection and deprotection proved to be big hurdles. All the different protection groups and different sequences of protection and deprotection we tried failed to get us through the designed synthetic sequence and furnish the final product. Most likely, the indole part is the culprit behind the failures.The NH group of the indole, no matter protected or not, may impact the catalytic asymmetric reduction of C-N double bond connected with 2-C. Additionally, the reduction product we designed contains an amino group in the β-position of the indole, which may cause problems due to its instability. C-sulfenylation of enamines is a novel reaction discovered recently by our group, which has not been seen before in the literature. In this study, optimization of the reaction conditions and exploration of the substrate scope were further undertaken for this reaction, which reveal that a series of enamines with N-Cbz, Ac, COt-Bu, CO2Et protection groups could all undergo smooth C-sulfinylations with the comined use of sodium benzene sulphinate, DAMc and MeSiCl3, efficiently furnishing the β-amino vinylsulfoxide products in high yield, affording a practical and highly efficient methods for synthesis of functional vinylsulfoxides.