【作者】 张丹；

【导师】 何仰清；

【作者基本信息】 西安理工大学 ， 化学工程与技术， 2022， 硕士

【摘要】 黄苞大戟(Euphorbia sikkimensis)是大戟科(Euphorbiaceae)大戟属(Euphorbia)植物,在中国广西、贵州、湖北、四川、云南和西藏等地广泛分布。其根入药,常用于肾炎水肿、腹胀、便秘、疟疾、风湿和黄疸等疾病的治疗。该属植物的主要有效成分为二萜类化合物,具有抗肿瘤、抗炎、抗菌、抗HIV等药理活性。黄毛翠雀花(Delphinium chrysotrichum)是毛茛科(Ranunculaceae)翠雀属(Delphinium)植物,分布于中国四川西部(康定以南)、西藏东部(朗县、察隅)地区。根据文献报道,该植物可供药用,可用于治疗跌打损伤、风湿、牙痛、肠炎等疾病。本文以黄苞大戟的根和黄毛翠雀花为研究对象,通过现代色谱分离技术,对两种植物进行了化学成分研究,并测试了部分化合物的抗乳腺癌活性。主要工作总结如下:综述了大戟属(Euphorbia)植物的化学成分和生物活性的研究进展,对来源于该属植物的茎、枝、叶等部位分离得到189个化合物按照结构类型进行了归纳和整理,并总结了其药理活性。运用常压柱色谱和高效液色谱(HPLC)等多种现代色谱分离手段,从黄苞大戟的根中分离得到6个化合物(1-6)。应用1H,13C NMR,质谱数据,并结合参考文献分别将其鉴定为:10-epi-e nt-(13S)-hydroxyatis-16-ene-3,14-dione(1)、ent-(5β,8α 9β,10α,11α,12α)-11-hydroxyatis-16-ene-3,14-di one(2)、ent-kaurane-3-oxo-16β,17-diol(3)、ent-kaurane-3-oxo-16α,17-diol(4)、ent-16α,17-dihydrox yatisane-3-one(5)、(2R 3S,4R,5R,6R,9S.11S,15R)-15b-cinna-moyloxy-5α,6β-epoxy-3β,16-dihydroxy-14-oxolathyr-12E-ene(6)。其中,化合物2,4,6为首次从黄苞大戟中分离得到的化合物。另外,从黄毛翠雀花中共分离得到9个化合物(7-15)。通过1D、2D NMR,高分辨质谱,并结合参考文献分别鉴定为:delphatisine D(7)、chrysotrichumine A(8)、sharwuphinine A(9)、davidisine B(10)、delsemineA(11)、delavaine A(12)、isodelpheline(13)、delpheline(14)、delcorine(15)。其中,化合物7和8为未见报道过的新化合物。化合物delphatisine D(7)为从翠雀属种分离得到的在C-7和C-20间具有甲醇胺醚(N-C-O-C)官能团的稀有阿替生型二萜生物碱。化合物chrysotrichumine A(8)为一个在C-17和C-19间具有硝酮结构单元稀有C19型二萜生物碱。采用MTT法,对黄毛翠雀花中分离得到的化合物7、9-11测试了抗人乳腺癌细胞系MCF-7和MDA-MB-231的细胞毒性。实验结果表明,所有的化合物都对MCF-7和MDA-MB-231细胞系均无细胞毒抑制活性,但化合物11在100μM时,对MDAMB-231细胞系表现出轻微的抑制活性,但未达到EC50。更多还原

【Abstract】 Euphorbia sikkimensis is a plant of the genus Euphorbia belonging to the tamily Euphorbiaceae,whicn is widely distributed in Guangxi,Guizhou,Hubei,Sichuan,Yunnan and Tibe of China.Its roots have been used in the treatment of nephritis,edema,bloating,constipation,malaria,rheumatism and jaundice.The major active ingredients of this genus are diterpene compounds with wide range pharmacological activities,such as anti-tumour,anti-inflammatory,anti-bacterial and anti-HIV activity.Delphinium chrysotrichum is one species of genus Delphinium from the family Ranunculaceae,which is mainly distributed in northwest of Sichuan(south of Kangding)and the eastern district of the Tibetan region(Langxian,Tsum)of mainland China.The plant has been used as Tibetan folk medicine for to treat bruises,rheumatism,toothache and enteritis disease.In this thesis,the roots of Euphorbia sikkimensis and the whole plant of Delphinium chrysotrichum were studied for exploring structural new and bioactivity compounds through modem chromatographic separation techniques,and some isolated compounds were tested for their anti-breast cancer activity.The major research works are summarized as following:First of all,we have reviewed the research progress of the chemical composition and biological activity of genus Euphorbia,and summarizes the 189 compounds isolated from the stem,branches and leaves of this genus according to their structural types,and their pharmacological activities.In charpter two,six compounds were isolated from the roots of Euphorbia sikkimensis(1-6)by silica gel column chromatography and high performance liquid chromatography(HPLC).They are:10-epi-ent-(13S)-hydroxyatis-16-ere-3,14-dione(1),ent-(5β,8α,9β,10α,11α,12α)-11-hydroxyatis-16ene-3,14-dione(2),ent-kaurane-3-oxo-16β,17-diol(3),ent-kaurane-3-oxo-16α,17-diol(4),ent-16α,17dihydroxyatisane-3-one(5),(2R,3S,4R,5R,6R,9S,11S,15R)-15b-cinna-moyloxy-5α,6β-epoxy-3β,16-dihy droxy-14-oxolathyr-12E-ene(6).Their structures were elucidated based on the extensive spectrosco pic analysis,including 1D,NMR,high resolution mass spectrum(HRMS),IR,and in comparison with the literatures.Among them,compounds 2,4 and 6 are the first time isolated from Euphor bia sikkimensis.In charpter three,we have investigated the aerial parts of D.chrysotrichum,which led to the isolation of a new C20-diterpenoid alkaloid,delphatisine D(7)and a new C19-diterpenoid alkaloid,chrysotrichumine A(8),along with seven known compounds:sharwuphinine A(9),davidisine B(10),delsemine A(11),delavaine A(12),isodelpheline(13),delpheline(14),delcorine(15).Their structures were elucidated on the basis of extensive spectroscopic analysis,including 1D,2D NMR,high resolution mass spectrometry,as well as in comparision with the data previously reported in literatures.Delphatisine D(7)is a rare atisinetype alkaloid from genus Delphinium and is the C-15 epimer of spiramine C which bears an internal carbinolamine ether linkage(N-C-O-C)between C-7 and C-20.Chrysotrichumine A(8)is a rare natural C19-diterpenoid alkaloid possessing a nitrone group between C-17 and C-19.Finally,the cytotoxicity of compounds 7,9-11 isolated from D.chrysotrichum was evaluated against human breast cancer cell lines MCF-7 and MDA-MB-231 using the MTT method,and the results indicated that all compounds were non-cytotoxic against both MCF-7 and MDA-MB-231 cell lines,but compound 11 showed slight activity against MDAMB-231 at 100μM,but did not reach the EC50.更多还原