本文選題：雞骨香　切入點(diǎn)：半枝蓮　出處：《中國(guó)科學(xué)院大學(xué)(中國(guó)科學(xué)院上海藥物研究所)》2017年博士論文　論文類型：學(xué)位論文

【摘要】：天然產(chǎn)物往往有著結(jié)構(gòu)新穎多變、生物活性廣泛等特點(diǎn),是創(chuàng)新藥物、藥物候選物和藥物先導(dǎo)物的重要來(lái)源。在眾多類型的天然產(chǎn)物中,二萜類成分是其中結(jié)構(gòu)類型最豐富和最重要的活性成分之一。許多著名的二萜類化合物如紫杉醇、關(guān)附甲素、銀杏內(nèi)酯類以及穿心蓮內(nèi)酯類均表現(xiàn)出較好的生物活性,這些活性化合物的發(fā)現(xiàn)使得二萜類化合物成為當(dāng)今天然藥物研究領(lǐng)域的熱點(diǎn)。本文對(duì)四種富含二萜類成分的藥用植物雞骨香(Croton crassifolius Geisel.)、半枝蓮(Scutellaria barbata D.Don)、腺梗宧薟(Sigesbeckia pubescens L.)和蔓荊子(Vitex rotundifolia L.)進(jìn)行了系統(tǒng)的化學(xué)成分研究,運(yùn)用Chromatorex C18、Chromatorex C8、MCI gel CHP-20P、TSK gel Toyopearl HW-40F、Sephadex LH-20、硅膠柱色譜及半制備高效液相色譜等分離手段對(duì)上述四種植物的提取物進(jìn)行系統(tǒng)的分離純化,通過(guò)波譜學(xué)技術(shù)、X-射線單晶衍射以及水解反應(yīng)等方法鑒定了108個(gè)化合物,包括86個(gè)二萜類化合物,其中新化合物33個(gè)。所發(fā)現(xiàn)的新化合物類型包括克羅烷型二萜、貝殼杉烷型二萜、海松烷型二萜、半日花烷型二萜、倍半萜糖苷、木脂素及黃酮等。根據(jù)藥用植物的民間用法結(jié)合多種藥理活性篩選模型,發(fā)現(xiàn)了部分具有良好生物活性的化合物。從雞骨香(Croton crassifolius Geisel.)根的丙酮提取物中分離鑒定了57個(gè)化合物,包括42個(gè)二萜(1-42),12個(gè)倍半萜(43-54)及木脂素等成分(55-57),其中化合物1-18為新的二萜,化合物1-4是B環(huán)或A環(huán)發(fā)生重排的二萜,化合物18是自然界中比較少見(jiàn)的綽奇烷型二萜�；衔�43是一個(gè)新的倍半萜糖苷類化合物,是首次報(bào)道該植物含有倍半萜糖苷類成分。從半枝蓮(Scutellaria barbata D.Don)全草的丙酮提取物中分離鑒定了10個(gè)化合物,全部為新克羅烷型二萜(58-67),其中化合物scubatins A-F(58-63)為新化合物,化合物61-63為含有螺環(huán)的新克羅烷型二萜。從腺梗宧薟(Sigesbeckia pubescens L.)全草的丙酮提取物中分離鑒定了25個(gè)化合物,包括18個(gè)貝殼杉烷型及海松烷型二萜(68-85),4個(gè)倍半萜(86-89)及木脂素、黃酮等成分(90-92)。新化合物有5個(gè),其中有2個(gè)對(duì)映貝殼杉烷型二萜(68-69),1個(gè)對(duì)映海松烷型二萜(79),1個(gè)木脂素(91)和1個(gè)黃酮二聚體(92),3個(gè)新的二萜類化合物均通過(guò)銅靶X-射線單晶衍射技術(shù)確定了絕對(duì)構(gòu)型。從蔓荊子(Vitex rotundifolia L.)果實(shí)的乙醇提取物中分離鑒定了16個(gè)化合物,全部為二萜類化合物,其中化合物93/94為新的含有螺環(huán)結(jié)構(gòu)的半日花烷型二萜,化合物96為新的含有對(duì)羥基苯甲酸取代的半日花烷型二萜。對(duì)所分離到的二萜類化合物進(jìn)行進(jìn)一步的藥理活性研究。細(xì)胞毒活性測(cè)試結(jié)果表明化合物9/10、20、22、63、66和74顯示出不同程度的細(xì)胞毒活性,IC50為5.2-32.7μM。Di I-LDL細(xì)胞吞噬實(shí)驗(yàn)表明化合物19和39表現(xiàn)出中等程度的降脂活性。
[Abstract]:Natural products are often characterized by novel structure and wide biological activity. They are important sources of innovative drugs, drug candidates and drug precursors. The diterpenoids are one of the most abundant and important active components in which many famous diterpenoids such as paclitaxel Ginkgolide ginkgolide and andrographolide have good bioactivity. The discovery of these active compounds has made diterpenoids a hot spot in the field of natural medicine research. In this paper, four medicinal plants, Croton crassifolius Geisel.Or, Scutellaria barbata D. Dondonia, Sigesbeckia pubescens L., are studied. The chemical constituents of Vitex rotundifolia L. were systematically studied. The extracts of the four plants were systematically separated and purified by means of Chromatorex C18, Chromatorex C8, MCI gel CHP-20P, TSK gel Toyopearl HW-40F Sephadex LH-20, silica gel column chromatography and semi-preparative high performance liquid chromatography. A total of 108 compounds, including 86 diterpenoids, were identified by spectroscopic techniques such as X-ray single crystal diffraction and hydrolysis. The diterpenoids of kauricotaxane, diterpene, diterpene, sesquiterpene glycoside, lignin and flavonoids were selected according to the folk usage of medicinal plants and various pharmacological activity screening models. 57 compounds, including 42 diterpenoids 1-42, 12 sesquiterpenes 43-54) and lignin, were isolated and identified from the acetone extract from the roots of Croton crassifolius Geisel.Of them, compounds 1-18 were new diterpenes. Compound 1-4 is a diterpene that rearranges B or A ring, compound 18 is a rare deterpene in nature. Compound 43 is a new sesquiterpene glycoside compound. It is the first time that the plant contains sesquiterpenoid glycosides. Ten compounds were isolated from the acetone extract of Scutellaria barbata D. Don. all of them were neocoroalkane diterpenoids 58-67, among which scubatins A-F 58-63) were new compounds. Compound 61-63 was a neocoroane diterpene containing snails. 25 compounds were isolated and identified from acetone extract of Sigesbeckia pubescens L., including 18 diterpenes of kapurane and kapodine, and 4 sesquiterpenes, 86-89) and lignin, respectively. Flavonoids, etc., from 90 to 92. There are 5 new compounds. Among them, there are two enantiotaxane diterpenoids 68-69, one enantiosporine diterpene 79, one lignin 91) and one flavonoid dimer, and three new diterpenoids have been determined by copper target X-ray single crystal diffraction technique. Sixteen compounds were isolated and identified from the ethanol extract of Vitex rotundifolia L. All of them are diterpenoids, of which compound 93/94 is a new type of diterpenoid with spiroid structure. Compound 96 is a new diterpenoid containing substituted p-hydroxybenzoic acid. Further pharmacological activity of the isolated diterpenoid compounds was studied. The cytotoxic activity of IC50 was 5.2-32.7 渭 M.Di I-LDL cells phagocytosis assay showed that compounds 19 and 39 showed moderate lipid-lowering activity.
【學(xué)位授予單位】：中國(guó)科學(xué)院大學(xué)(中國(guó)科學(xué)院上海藥物研究所)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類號(hào)】：R284

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