天然产物Standishinal 的首次全合成研究

具有1，1，4α-三甲基氢化芴骨架结构的天然三环二萜化合物自然界中不常见。在该类化合物中，Standishinal 具有良好的芳香化酶抑制活性和细胞毒活性。迄今未发现有Standishinal 的全合成报道，因此，我们对Standishinal 的全合成进行了探索，在该过程中得到以下实验结果： 1. 发现MSA/P2O5、MSA 在无溶剂条件下，25 °C 时烷氧基苯即可实现向苯酚的转化，但在CH3NO2 中，温度升高至80 °C 并未发生反应。 2. 烷氧基苯或对溴苯酚与α-环香叶酸在不同温度下以MSA/P2O5、MSA、PPA为催化剂以CH3NO2 为溶剂或以BF3·Et2O为催化剂时均不发生Friedel-Crafts酰化反应。 3. 对溴苯酚与香叶酸在p-TsOH 催化作用下发生了香叶酸向α-环香叶酸环化、α-环香叶酸环与对溴苯酚的酯化，得到了唯一产物α-环香叶酸对溴苯酯，产率68%。 Standishinal is one of tricyclic-diterpenes possessing the uncommon 1, 1,4a-trimethylhydrofluorene skeleton. Standishinal possesses cytotoxic and aromataseinhibitory activities. Till now, no synthesis of standishinal has been reported. Inattempt to synthesize standishinal, the following phenomenon were observed: 1. Alkyloxybenzenes could be transformed into corresponding phenol at 25 °C inthe presence of MSA/P2O5 or MSA under solvent free condition. ButAlkyloxybenzenes are stable in presence of MSA/P2O5 or MSA in CH3NO2 even at 80 °C. 2. Friedel-Crafts acylation of alkyloxybenzenes and p-bromophenol withα-cyclogeranic acid could not be realized under catalysis of MSA/P2O5, MSA or PPAin CH3NO2, or under catalysis of BF3·Et2O without CH3NO2. 3. The reaction of 4-bromaophenol and geranic acid in the presecnce of p-TsOHafforded 4-bromophenol α-cyclogeranoate in which cyclization of geranic acid toα-cyclogeranic acid was followed by esterification of α-cyclogeranic acid with p-bromophenol.

Tetranorclerodanes and clerodane-type diterpene glycosides from Dicranopteris dichotoma

The acetone extract of Dicranopteris dichotoma afforded two new tetranorclerodanes, 18-hydroxyaylthonic acid (1) and 18-oxo-aylthonic acid (2), and four new clerodane-type diterpene glycosides, (6S,13S)-6-O-[6-O-acetyl-beta-D-glucopyranosyl-(1 -> 4)-alpha

A novel hydroperoxyl substituted cembranolide diterpene from marine soft coral Lobophytum crassum

A new cembranolide diterpene with a hydroperoxyl substitution was isolated from the marine soft coral Lobophytum crassum. The structure was elucidated on the basis of chemical and spectral methods.

An ent-Kaurane Diterpene from Euphorbia wallichii

One known ent- kaurane diterpene, ent- 16α, 17- dihydroxykauran- 3-one, were isolated from the roots of Euphorbia wallichii for the first time. Its structure was elucidated on the basis of spectral methods. And the NMR assignments of the compound in CD3OD were given for the first time.

A new daphnane diterpene from Daphne tangutica

A new daphnane diterpene was isolated from the root barks of Daphne tangutica Maxim. Its structure was elucidated as 1, 2 alpha-dihydro-20-palimoyldaphnetoxin by the spectroscopic evidence including 2D-NMR.

附子及乌头属植物中二萜类生物碱的电喷雾质谱研究

电喷雾质谱是一种软电离技术，生物碱分子中均含有氮原子，具有很高的质子亲合势和气相碱度，特别适合电喷雾质谱分析。本文利用电喷雾质谱系统研究了乌头属的几种植物中二菇类生物碱的质谱行为。并且对中药复方中的生物碱成分的化学变化进行探讨，在串联质谱中，乌头碱类生物碱的裂解方式相似。双酷型、三醋型、脂类生物碱在MS2中容易丢失C8乙酸或长链脂肪酸形成特征子离子峰，在进一步CID谱中，在C15位失去CO为其特征。但是单酷型生物碱在串联质谱中碎裂方式与上述几种生物碱有很大差别，例如，在MSZ中主要失去甲醇，还会失去C3位经基，但是不会失去CS轻基。利用这些规律分析了附子及草乌中的生物碱，发现了多种具有特殊取代基的新化合物。以电喷雾质谱为检测手段分析了附子在炮制过程中的成分变化；并且发现了分离提取脂类生物碱的方法。高乌头中的生物碱以C18型为主，同时也包含少量C19乌头碱骨架的生物碱。这两种类型的生物碱在串联质谱中的碎裂规律相似，都容易失去取代基，而生物碱骨架比较稳定，难以碎裂。但是不同位置的取代基失去时所形成的子离子的丰度有很大差别，经过串联质谱可以获取重要的结构信息。并且通过串联质谱确定了刺乌头碱环糊精的包合位点，更正了文献中的错误。关白附的CZ。型海替生型生物碱在串联质谱中的行为与上述生物碱相似，容易失去取代基，但是在失去取代基的同时，常常伴随骨架中C-C键的断裂。由于这些生物碱的结构存在较强的规律，所以很容易表征其中的结构相似的新生物碱。另一方面，我们发现导致白术与附子配伍将导致共煎液中有毒生物碱成分增加，从而解释了八味地黄丸与人参汤导致中毒的原因。并且通过对八味地黄汤的配伍研究，发现起解毒作用的药材为山茱英，解毒机理为抑制了有毒生物碱的溶出。方中的山药能够抑制双酷型生物碱的水解。

唐古特瑞香和大果大戟的化学成分研究

本学位论文由两部分共3章组成。第一部分分别报道2种藏药唐古特瑞香和大果大戟化学成分的研究成果，从2种药用植物共分离鉴定了60个不同的化合物，其中12个为新结构，特别有意义的是发现了2个具有同一新骨架的二萜化合物。第二部分概述了大戟科植物多环二萜的研究进展。 第一部分包括第1和2章。在这2章中分别报道了唐古特瑞香（Daphne tangutica Maxim）和大果大戟（Euphorbia wallichii Hook. f. Fl）化学成分的分离纯化与结构鉴定。实验采用正、反相硅胶柱层析、薄层制备及HPLC等分离方法，从唐古特瑞香的根皮中共分离出32个化合物，通过红外、质谱及核磁共振等波谱方法鉴定了其中的31个，结构类型分别属于瑞香二萜类、木脂素类、香豆素类、苯丙素类及甾体类，其中有三个新的瑞香二萜型化合物，经波谱分析将它们的结构分别鉴定为1,2a-二氢-20-棕榈酰瑞香毒素、1,2a-二氢-5b-羟基-6a,7a-环氧-树脂大戟醇-14-苯甲酸酯及1,2b-二氢-5b-羟基-6a,7a-环氧-树脂大戟醇-14-苯甲酸酯，另外还有13个已知化合物为首次从该植物中分离得到。从大果大戟的根部共分离出33个化合物，鉴定了其中的30个，其主要成分为种类丰富的二萜，包括巨大戟烷型、续随子烷型、对映－阿替生烷型、对映－贝壳杉烷型、对映－松香烷型、ent-trachylobane型、对映－异海松烷型及一新骨架五环二萜ent-wallichane型，另外还有香豆素、甾体、三萜和一些简单的小分子化合物。其中新化合物有9个，经波谱分析将它们的结构分别鉴定为5-O-(2E,4E,6E)-癸三烯酰基-3,20-O-二乙酰基巨大戟醇、5-O-(2E,4Z)-癸二烯酰基-3-O-乙酰基-20-去氧巨大戟醇、3-O-(2E,4Z)-癸二烯酰基-5b,6b-氧-交京大戟醇、7-苯甲酰氧基-3,5,15-三乙酰基-续随子醇、ent-trachylobane-3-one-17-oic-acid、3α-羟基-对映-阿替斯-16-烯-14-酮、3α,6-二羟基-对映-异海松-7-烯-2,15-二酮、wallichanol A 和 wallichanol B，其中，wallichanol A 和 wallichanol B属于一新骨架类型的五环二萜。除此以外，另有13个已知化合物为首次从该植物中分离得到。 第2部分即第3章，首次概述了大戟属植物中多环二萜的化学和药理研究进展。 This dissertation is composed by two parts. The first part reports the phytochemical investigation of two Tibetan medicine plants, Daphne tangutica Maxim and Euphorbia wallichii Hook. f. Fl. Sixty different compounds including ten new compounds and two novel diterpenoids possessing a new carbon skeleton were isolated and identified. The second part is a review about the progress of studies on the polycyclic diterpeniods of the plant family of Euphorbia. The first part consists two chapters, which expatiate on the isolation and identification of chemical constituents from D. tangutica and E. wallichii. Thirty-one compounds were isolated from the root barks of D. tangutica by methods of column chromatography (silica gel, including reversed phase), preparative TLC and HPLC, and their structure were identified as nine daphnane diterpenes, six lignans, nine cumarin derivatives, five phenylpropanoid derivatives, a steroids and a benzoate on the basis of spectroscopic methods including IR, MS and NMR. Among them, three are new diterpenes with skeleton of daphnane and the structure were determined as 1,a-dihydro-20-palimoyl-daphnetoxin, 1,2a-dihydro-5b- hydroxy-6a,7a-epoxy-resiniferonol-14-benzoate and 1,2b-dihydro-5b-hydroxy- 6a,7a-epoxy-resiniferonol-14-benzoate. In addition, thirteen known ones were isolated from this plant for the first time. Isolation of the roots of E. wallichii yielded thirty compounds, twenty-four of them were elucidated as diterpenoids, which belong to different skeleton types of ingenol, lathyrane, ent-atisane, ent-kaurane, ent-abietane, ent-trachylobane, ent-isopimarane and a new pentacyclic skeleton ent-wallichane respectively. The remains including a cumarine, a triterpenoid, a steroid and three compounds with small molecule. Nine new compounds were characterized as 5-O-deca-2E,4E,6E- trienoyl-3,20-O-diacetylingenol, 5-O-deca-2E,4Z-dienoyl-3-O-acetyl-20- deoxyingenol, 3-O-deca-2E,4Z-dienoyl-jolkinol-5b,6b-oxide, 7-benzoyl-3,5,15- triacetyl-7-hydroxylathyrol, ent-trachylobane-3-one-17-oic-acid, 3α-hydroxy-ent- atis-16-en-14-one, 3α,6-dihydroxy-ent-isopimarane-7-en-2,15-dione, wallichanol A and wallichanol B, respectively, by means of comprehensive spectroscopic analysis. Among them, wallichanol A and wallichanol B were two notable novel pentacyclic diterpenoids processing a new rearranged carbon skeleton. And more, thirteen ones were firstly reported from this plant. The third chapter summarizes the research development on chemistry and pharmacology of polycyclic diterpenes from the plant family of Euphorbia for the first time.

余甘子、细叶草乌及土荆皮化学成分研究

本论文由三部分共6 章组成。第一部分报道了余甘子、细叶草乌和土荆皮等三种药用植物的化学成分研究成果；第二部分报道了细叶草乌和土荆皮中分离得到的化合物的活性测试，以及这两种植物的质谱分析；第三部分概述了土荆皮的研究现状。第一部分包括1－3 章。在第1 章、第2 章和第3 章中分别报道了余甘子(Phyllanthus emblica L.) 、细叶草乌(Aconitum richardsonianum var.pseudosessiliflorum) 和土荆皮( pseudolarix kaempferi) 的化学成分。采用正、反相硅胶柱层析等各种分离方法，从余甘子中共分离出10 个化合物，其中1 个为新化合物，另外还有2 个为首次从该植物中分离得到。细叶草乌的化学成分研究尚未见报道，我们从该植物中共分离出15 个化合物，其中6 个为二萜生物碱，9个为非生物碱成分。从土荆皮中分离得到16 个化合物，其中8 个二萜、1 个三萜和7 个其它类型化合物，其中有4 个化合物为首次在该植物中分离得到；从土荆皮挥发油中分离鉴定出了22 个化合物，占挥发油总量的90%。第二部分包括4－5 章。第4 章报道了从细叶草乌和土荆皮中分离得到的13个化合物的药理活性研究，结果显示，展花乌头宁和土荆乙酸葡萄糖苷等表现出较高的组织蛋白酶K 抑制活性；土荆乙酸葡萄糖苷表现出较高的组织蛋白酶B抑制活性；8-去乙酰滇乌碱表现出较高的蛋白质酪氨酸磷酸酶抑制活性。第5 章报道了细叶草乌和土荆皮总浸膏的质谱( ESI-MS ) 分析，研究结果表明，ESI-MS 法可以简单快速地检测这两种植物的主要成分；通过ESI-MS2 分析初步探讨了一些化合物的裂解规律，尝试质谱在其结构测定中的具体应用。第三部分为第6 章。从化学成分、药理、构效关系、主要成分的定量分析、及其合成研究等方面概述了土荆皮的研究进展。 This dissertation consists of three parts. The first part elaborate thephytochemical investigation of three medicinal plants, Phyllanthus emblica L.,Aconitum richardsonianum var. pseudosessiliflorum and pseudolarix kaempferi. Thesecond part reported the bioassay of 13 constituents from Aconitum richardsonianumvar. pseudosessiliflorum and pseudolarix kaempferi, and ESI-MS analysis of these twoplant . The third part is a review on the research progress of pseudolarix kaempferi.The first part is composed of three chapters. Chapters 1-3 focus on the isolationand identification of chemical constituents from Phyllanthus emblica L., Aconitumrichardsonianum var. pseudosessiliflorum and pseudolarix kaempferi. 10 compoundsincluding a new tannin were isolated from the fruits of Phyllanthus emblica by repeatcolumn chromatography over normal and reversed phase silica gel, 2 of them werefirstly reported in this plant. The chemical constituents of Aconitum richardsonianumvar. pseudosessiliflorum never reported before, 15 compounds including 6 diterpenealkaloids were isolated and identified from the roots of this plant. 16 compoundsincluding 8 diterpenes , 1 triterpene and 7 other compounds were isolated from the bark of pseudolarix kaempferi, among them, 4 compounds were firstly reported fromthe EtOH extracts of this plant, and 22 compounds were identified from its essentialoil, representing 90% of the total essential oil.The second part includes chapters 4 and 5. Chapter 4 reported thepharmacological activities of 13 compounds isolated from Aconitum richardsonianumvar. pseudosessiliflorum and pseudolarix kaempferi. Results demonstrated that chasmanine and pseudolaric acid B-β-D-glucoside exhibit relatively high anti-Cathepsin K activities; pseudolaric acid B-β-D-glucoside exhibits relatively highanti-Cathepsin B activity; 8-deacetyl-yunaconitine exhibits relatively high anti-PTP1Bactivity. Chapter 5 reported the ESI-MS analysis of extractions from Aconitumrichardsonianum var. pseudosessiliflorum and pseudolarix kaempferi, it was showedthat ESI-MS can be used as an useful tool in analyzing the major constituents of thesetwo plant much quick and easy, in addition, the fragmentation rules of somecompounds were discussed, in order to find some applications of ESI-MS2 method in their structure determination.The third part is a review on the research progress of pseudolarix kaempferi,including the chemical constituents, pharmacology, structure-activity relationship(SAP), quantitative analysis and synthesis of the major constituents.

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.