WO2019114525A1 - Cucurbitacin derivative and preparation method therefor - Google Patents

Cucurbitacin derivative and preparation method therefor Download PDF

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WO2019114525A1
WO2019114525A1 PCT/CN2018/117201 CN2018117201W WO2019114525A1 WO 2019114525 A1 WO2019114525 A1 WO 2019114525A1 CN 2018117201 W CN2018117201 W CN 2018117201W WO 2019114525 A1 WO2019114525 A1 WO 2019114525A1
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formula
cucurbitacin
added
dissolved
derivative
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PCT/CN2018/117201
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French (fr)
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张南
钟荣
谭国良
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张南
钟荣
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C07J41/0005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring the nitrogen atom being directly linked to the cyclopenta(a)hydro phenanthrene skeleton
    • C07J41/0011—Unsubstituted amino radicals

Definitions

  • the present application relates to various derivatives of cucurbitacin, in particular to various derivatives of cucurbitacin B and cucurbitacin E, and to a process for the preparation of these derivatives.
  • Cucurbitacin belongs to the class of tetracyclic triterpenoids with a 19-methyl group at the C-9 position. It is mainly distributed in the cucurbitaceae plant, in the cruciferae, Scrophulariaceae, Begonia, Du Yingke, and the number four. It has also been found in higher plants such as wood and some large fungi.
  • Cucurbita melon L. cucurbita extract which has a variety of biological activities, has detoxification and heat, dampness and yellowing effect, and is clinically effective for treating chronic hepatitis and primary liver cancer. Chinese patent medicine.
  • the reported pharmacological effects include: cytotoxicity and anticancer effects; anti-chemical carcinogenesis; liver protection, anti-hepatitis effect; improving immune function; cardiovascular effects; anti-inflammatory; inhibiting liver fibrosis; Intestinal exercise, but also contraception.
  • the first object of the present application is to provide various new derivatives of cucurbitacin B and cucurbitacin E and salts thereof; the second object of the present application is to provide a method for preparing a new derivative of cucurbitacin B and cucurbitacin E .
  • the present application provides 20 new derivatives of cucurbitacin B, 20 new derivatives of cucurbitacin E and pharmaceutically acceptable salts thereof.
  • the chemical structures of these new derivatives are as follows:
  • the cucurbitacin E derivative of formula E-2 which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
  • a cucurbitacin E derivative of formula E-8 which is characterized by nuclear magnetic resonance spectroscopy to determine its molecular weight:
  • a cucurbitacin E derivative of formula E-10 which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
  • the cucurbitacin E derivative of formula E-11 which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
  • a cucurbitacin E derivative of formula E-12 which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
  • the cucurbitacin E derivative of formula E-13 which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
  • a cucurbitacin E derivative of formula E-14 which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
  • a cucurbitacin E derivative of formula E-15 which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
  • the cucurbitacin E derivative of formula E-17 which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
  • the cucurbitacin E derivative of formula E-18 which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
  • the cucurbitacin E derivative of formula E-19 which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
  • the cucurbitacin E derivative of formula E-21 which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
  • a cucurbitacin E derivative of formula E-22 which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
  • a cucurbitacin E derivative of formula E-23 which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
  • a cucurbitacin E derivative of formula B-10 which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
  • the cucurbitacin E derivative of formula B-13 which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
  • the cucurbitacin E derivative of formula B-15 which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
  • the cucurbitacin E derivative of formula B-19 which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
  • the cucurbitacin E derivative of formula B-21 which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
  • the compound B-15, the formula B-16, the formula E-15 and the formula E-16 are obtained by hydrolyzing lithium hydroxide of the formula B-11, the formula B-12, the formula E-11 and the formula E-12, respectively.
  • the compound formula B-17, formula B-18, formula B-19, formula B-20, and formula B-23 are respectively from formula E-17, formula E-18, formula E-19, formula E-20, formula E- 23 is obtained by reduction, and the formula E-24 is obtained by catalytic hydrogenation reduction of the formula E-23, and the formula B-24 is obtained by reduction of the formula E-24.
  • the compound of the formula E-25 and the formula E-26 are respectively obtained by hydrolysis of the formula E-21 and the formula E-22, and the compound of the formula B-21, the formula B-22, the formula B-25 and the formula B-26 are respectively obtained from the compound formula E- 21.
  • Formula E-22, E-25, and E-26 are obtained by reduction.
  • the newly discovered 20 kinds of cucurbitacin B derivatives and 20 kinds of cucurbitacin E derivatives and their salts have the same basic structure with cucurbitacin B and cucurbitacin E respectively, so the properties are basically the same with cucurbitacin B and gourd. Like E, it has good anti-cancer, anti-viral, anti-inflammatory and liver-protecting effects, and has low toxic side effects.
  • E-16 synthesis E-12 (73 mg, 0.1 mmol) was dissolved in 5 methanol, then 1N aqueous lithium hydroxide solution (100 ⁇ L, 0.1 mmol), stirred at room temperature for 1 hour, the reaction After completion, the residue was evaporated to dichloromethane.
  • E-23 synthesis E-23-02 was dissolved in methanol, then added 1N aqueous lithium hydroxide solution, stirred at room temperature for 2 hours, concentrated, the residue was dissolved in dichloromethane, washed with alkaline water, organic layer Dry and concentrated to give a white solid as E-23.
  • Human vascular endothelial cell line (HUVEC) cells were cultured for 8 hours in human recombinant vascular endothelial growth factor culture medium supplemented with different concentrations of cucurbitacin E or cucurbitacin E derivative and containing 10 nM at the same time. The cells were treated to detect STAT3 phosphorylation activity in HUVEC cells. The results were as follows:
  • the new derivative of cucurbitacin B and the new derivative of cucurbitacin E have the same functions as the existing cucurbitacin B and cucurbitacin E, and have anti-cancer, anti-viral, anti-inflammatory and hepatoprotective effects.
  • the pharmacological methods for studying these new cucurbitacin B and E derivatives are the same as the existing cucurbitacin B and cucurbitacin E, so the pharmacological effects of the existing cucurbitacin B and cucurbitacin E are not described here.
  • the report specifically refers to the documents disclosed below:

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  • Organic Chemistry (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present application discloses a plurality of novel derivatives of cucurbitacin B and cucurbitacin E, and salts thereof, and also discloses methods for preparing these novel derivatives. These new derivatives and their salts have common basic structures with cucurbitacin B and cucurbitacin E, respectively, and therefore have basically the same properties as those of cucurbitacin B and cucurbitacin E, i.e., good anti-cancer, anti-viral, anti-inflammatory, and liver-protecting effects, and low toxic side effects.

Description

葫芦素衍生物及其制备方法Cucurbitacin derivative and preparation method thereof
本申请是以申请号为201711347172.6，申请日为2017年12月15日的中国专利申请为基础，并主张其优先权，该申请的全部内容在此作为整体引入本申请中。The present application is based on a Chinese patent application filed on Jan. 15, 2017, the entire disclosure of which is hereby incorporated by reference.
技术领域Technical field
本申请涉及葫芦素的多种衍生物，具体涉及葫芦素B和葫芦素E的多种衍生物，还涉及这些衍生物的制备方法。The present application relates to various derivatives of cucurbitacin, in particular to various derivatives of cucurbitacin B and cucurbitacin E, and to a process for the preparation of these derivatives.
背景技术Background technique
葫芦素(cucurbitacin)属于19-甲基出现在C-9位上的一类四环三萜化合物，主要分布于葫芦科植物中，在十字花科、玄参科、秋海棠科、杜英科、四数木科等高等植物及一些大型真菌中也有发现。葫芦素系葫芦科植物甜瓜(Cucumis melo L.)瓜蒂的提取物，它具有多种生物活性，具有解毒清热，利湿退黄作用，是临床上用于治疗慢性肝炎和原发性肝癌有效中成药。Cucurbitacin belongs to the class of tetracyclic triterpenoids with a 19-methyl group at the C-9 position. It is mainly distributed in the cucurbitaceae plant, in the cruciferae, Scrophulariaceae, Begonia, Du Yingke, and the number four. It has also been found in higher plants such as wood and some large fungi. Cucurbita melon L. cucurbita extract, which has a variety of biological activities, has detoxification and heat, dampness and yellowing effect, and is clinically effective for treating chronic hepatitis and primary liver cancer. Chinese patent medicine.
我国古代就采用中药甜瓜(Cucumis melo L.)蒂治黄疸病，又能催吐、祛痰，用于痰涎宿食，60年代开始随着葫芦素化学结构的确立，国外有人研究其抗肿瘤作用。国内70年代初从中药甜瓜蒂中分离出葫芦素B、E等成分，并进行了抗肿瘤、免疫增强和抗肝炎等药理研究。报道的药理作用有：细胞毒与抗癌作用；抗化学致癌作用；保肝、抗肝炎作用；提高免疫功能；对心血管的作用；抗炎；抑制肝纤维增生的作用；此外还有刺激胃肠运动，还可避孕。In ancient China, Chinese traditional medicine melon (Cucumis melo L.) was used to treat jaundice, and it can induce vomiting and phlegm. It was used for sputum feeding. In the 1960s, with the establishment of cucurbitacin chemical structure, foreign people studied its anti-tumor effect. . In the early 1970s, cucurbitacin B and E were separated from the Chinese medicine melon stalk, and pharmacological studies such as anti-tumor, immune enhancement and anti-hepatitis were carried out. The reported pharmacological effects include: cytotoxicity and anticancer effects; anti-chemical carcinogenesis; liver protection, anti-hepatitis effect; improving immune function; cardiovascular effects; anti-inflammatory; inhibiting liver fibrosis; Intestinal exercise, but also contraception.
申请内容Application content
本申请的第一个目的是提供葫芦素B和葫芦素E的多种新衍生物和它们的盐；本申请的第二个目的是提供葫芦素B和葫芦素E的新衍生物的制备方法。The first object of the present application is to provide various new derivatives of cucurbitacin B and cucurbitacin E and salts thereof; the second object of the present application is to provide a method for preparing a new derivative of cucurbitacin B and cucurbitacin E .
本申请提供了20种葫芦素B的新衍生物、20种葫芦素E的新衍生物以及它们的药学上可接受的盐，这些新衍生物的化学结构如下：The present application provides 20 new derivatives of cucurbitacin B, 20 new derivatives of cucurbitacin E and pharmaceutically acceptable salts thereof. The chemical structures of these new derivatives are as follows:
Figure PCTCN2018117201-appb-000001
Figure PCTCN2018117201-appb-000001
Figure PCTCN2018117201-appb-000002
Figure PCTCN2018117201-appb-000002
Figure PCTCN2018117201-appb-000003
Figure PCTCN2018117201-appb-000003
Figure PCTCN2018117201-appb-000004
Figure PCTCN2018117201-appb-000004
Figure PCTCN2018117201-appb-000005
Figure PCTCN2018117201-appb-000005
式E-1的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula E-1, which is characterized by nuclear magnetic resonance spectroscopy, and its molecular weight is calculated by mass spectrometry:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.66(s，1H)，6.29(d，J＝12Hz，1H)，5.51(t，J＝8.4Hz，1H)，3.23(m，1H)，2.85(m，1H)，2.29-2.27(m，3H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.36(s，6H)，1.30(s，3H)，1.14(t，J＝8.4，3H)，1.04(s，6H)；MS 571[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.66 (s, 1H), 6.29 (d, J = 12 Hz, 1H), 5.51 (t, J = 8.4 Hz, 1H), 3.23 (m, 1H), 2.85 (m, 1H), 2.29-2.27 (m, 3H), 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 4H) , 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.36 (s, 6H), 1.30 (s, 3H), 1.14 (t, J = 8.4, 3H), 1.04 (s, 6H); MS 571 [M+H] + .
式E-2的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula E-2, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.66(s，1H)，6.29(d，J＝12Hz，1H)，5.51(t，J＝8.4Hz，1H)，3.23(m，1H)，2.85(m，1H)，2.32-2.27(m，3H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，6H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.36(s，6H)，1.30(s，3H)，1.04(s，6H)，0.90(t，J＝8.4，3H)；MS 585[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.66 (s, 1H), 6.29 (d, J = 12 Hz, 1H), 5.51 (t, J = 8.4 Hz, 1H), 3.23 (m, 1H), 2.85 (m, 1H), 2.32-2.27 (m, 3H), 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 6H) , 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.36 (s, 6H), 1.30 (s, 3H), 1.04 (s, 6H), 0.90 (t, J = 8.4, 3H); MS 585 [M+H] + .
式E-5的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula E-5, which is characterized by nuclear magnetic resonance spectroscopy and its mass spectrometry:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.66(s，1H)，6.29(d，J＝12Hz，1H)，5.51(t，J＝8.4Hz，1H)，5.03(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，3.23(m，1H)，2.85(m，1H)，2.29-2.27(m，6H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.36(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 719[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.66 (s, 1H), 6.29 (d, J = 12 Hz, 1H), 5.51 (t, J = 8.4 Hz, 1H), 5.03 (m, 1H), 3.79-3.49 (m, 5H), 3.40 (m, 1H), 3.23 (m, 1H), 2.85 (m, 1H), 2.29-2.27 (m, 6H), 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 4H), 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.36 (s , 6H), 1.30 (s, 3H), 1.04 (s, 6H); MS 719 [M+H] + .
式E-7的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula E-7, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ16.77(s，1H)，7.01(d，J＝12Hz，1H)，6.29(d，J＝12Hz，1H)，5.71(s，1H)，5.51(t，J＝8.4Hz，1H)，5.01(t，2H)，3.65-3.6(m， 2H)，3.32-3.23(m，2H)，2.85(m，1H)，2.29-2.27(m，3H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.36(s，6H)，1.30(s，3H)，1.14(t，J＝8.4，3H)，1.04(s，6H)；MS 572[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 16.77 (s, 1H), 7.01 (d, J = 12 Hz, 1H), 6.29 (d, J = 12 Hz, 1H), 5.71 (s, 1H), 5.51 ( t, J = 8.4 Hz, 1H), 5.01 (t, 2H), 3.65-3.6 (m, 2H), 3.32-3.23 (m, 2H), 2.85 (m, 1H), 2.29-2.27 (m, 3H) , 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 4H), 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.36 (s, 6H), 1.30 (s, 3H), 1.14 (t, J = 8.4, 3H), 1.04 (s, 6H); MS 572 [M+H] + .
式E-8的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：A cucurbitacin E derivative of formula E-8, which is characterized by nuclear magnetic resonance spectroscopy to determine its molecular weight:
1H-NMR(400MHz，CDCl 3)δ16.77(s，1H)，7.01(d，J＝12Hz，1H)，6.29(d，J＝12Hz，1H)，5.71(s，1H)，5.51(t，J＝8.4Hz，1H)，5.01(t，2H)，3.65-3.6(m，2H)，3.32-3.23(m，2H)，2.85(m，1H)，2.29-2.27(m，3H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，6H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.36(s，6H)，1.30(s，3H)，1.14(t，J＝8.4，3H)，1.04(s，6H)；MS 586[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 16.77 (s, 1H), 7.01 (d, J = 12 Hz, 1H), 6.29 (d, J = 12 Hz, 1H), 5.71 (s, 1H), 5.51 ( t, J = 8.4 Hz, 1H), 5.01 (t, 2H), 3.65-3.6 (m, 2H), 3.32-3.23 (m, 2H), 2.85 (m, 1H), 2.29-2.27 (m, 3H) , 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 6H), 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.36 (s, 6H), 1.30 (s, 3H), 1.14 (t, J = 8.4, 3H), 1.04 (s, 6H); MS 586 [M+H] + .
式E-9的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula E-9, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ15.72(s，1H)，5.71(m，1H)，5.37(t，J＝8.4Hz，1H)，4.91(m，2H)，3.63-3.55(m，3H)，3.44(m，1H)，3.23(m，1H)，2.29-2.27(m，3H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，12H)，1.60-1.46(m，2H)，1.43(s，6H)，1.38(s，3H)，1.25(s，6H)，1.30(s，3H)，1.14(t，J＝8.4，3H)，1.04(s，6H)；MS 574[M+H] +。 1 H-NMR (400MHz, CDCl 3) δ15.72 (s, 1H), 5.71 (m, 1H), 5.37 (t, J = 8.4Hz, 1H), 4.91 (m, 2H), 3.63-3.55 (m , 3H), 3.44 (m, 1H), 3.23 (m, 1H), 2.29-2.27 (m, 3H), 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 12H) ), 1.60-1.46 (m, 2H), 1.43 (s, 6H), 1.38 (s, 3H), 1.25 (s, 6H), 1.30 (s, 3H), 1.14 (t, J = 8.4, 3H), 1.04 (s, 6H); MS 574 [M+H] + .
式E-10的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：A cucurbitacin E derivative of formula E-10, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ15.72(s，1H)，5.71(m，1H)，5.37(t，J＝8.4Hz，1H)，4.91(m，2H)，3.63-3.55(m，3H)，3.44(m，1H)，3.23(m，1H)，2.29-2.27(m，3H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，14H)，1.60-1.46(m，2H)，1.43(s，6H)，1.38(s，3H)，1.25(s，6H)，1.30(s，3H)，1.14(t，J＝8.4，3H)，1.04(s，6H)；MS 588[M+H] +。 1 H-NMR (400MHz, CDCl 3) δ15.72 (s, 1H), 5.71 (m, 1H), 5.37 (t, J = 8.4Hz, 1H), 4.91 (m, 2H), 3.63-3.55 (m , 3H), 3.44 (m, 1H), 3.23 (m, 1H), 2.29-2.27 (m, 3H), 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 14H) ), 1.60-1.46 (m, 2H), 1.43 (s, 6H), 1.38 (s, 3H), 1.25 (s, 6H), 1.30 (s, 3H), 1.14 (t, J = 8.4, 3H), 1.04 (s, 6H); MS 588 [M+H] + .
式E-11的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula E-11, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ16.35(s，1H)，7.01(d，J＝12Hz，1H)，6.29(d，J＝12Hz，1H)，5.71(s，1H)，5.37(t，J＝8.4Hz，1H)，5.13(m，2H)，5.03(m，1H)，4.08(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，2.85(m，1H)，2.27-2.02(m，8H)，1.85-1.69(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.31(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 720[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 16.35 (s, 1H), 7.01 (d, J = 12 Hz, 1H), 6.29 (d, J = 12 Hz, 1H), 5.71 (s, 1H), 5.37 ( t, J = 8.4 Hz, 1H), 5.13 (m, 2H), 5.03 (m, 1H), 4.08 (m, 1H), 3.79-3.49 (m, 5H), 3.40 (m, 1H), 2.85 (m) , 1H), 2.27-2.02 (m, 8H), 1.85-1.69 (m, 4H), 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.31 (s, 6H) ), 1.30 (s, 3H), 1.04 (s, 6H); MS 720 [M+H] + .
式E-12的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：A cucurbitacin E derivative of formula E-12, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)15.82(s，1H)，5.71(s，1H)，5.35(t，J＝8.4Hz，1H)，5，09(b，2H)，5.03(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，3.23(m，1H)，2.85(m，1H)，2.29-2.27(m，10H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.36(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 722[M+H] +。 1 H-NMR (400MHz, CDCl 3 ) 15.82 (s, 1H), 5.71 (s, 1H), 5.35 (t, J = 8.4 Hz, 1H), 5, 09 (b, 2H), 5.03 (m, 1H) ), 3.79-3.49 (m, 5H), 3.40 (m, 1H), 3.23 (m, 1H), 2.85 (m, 1H), 2.29-2.27 (m, 10H), 2.16 (m, 1H), 2.04- 2.02(m,2H),1.86-1.71(m,4H),1.60-1.46(m,2H), 1.47(s,6H), 1.38(s,3H), 1.36(s,6H),1.30(s, 3H), 1.04 (s, 6H); MS 722 [M+H] + .
式E-13的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula E-13, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ16.77(s，1H)，7.01(d，J＝12Hz，1H)，6.29(d，J＝12Hz，1H)，5.71(s，1H)，5.51(t，J＝8.4Hz，1H)，5.01(t，2H)，3.65-3.6(m，2H)，3.32-3.23(m，2H)，2.85(m，1H)，2.29-2.27(m，3H)，2.16(m，1H)，1.86-1.71(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.36(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 516[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 16.77 (s, 1H), 7.01 (d, J = 12 Hz, 1H), 6.29 (d, J = 12 Hz, 1H), 5.71 (s, 1H), 5.51 ( t, J = 8.4 Hz, 1H), 5.01 (t, 2H), 3.65-3.6 (m, 2H), 3.32-3.23 (m, 2H), 2.85 (m, 1H), 2.29-2.27 (m, 3H) , 2.16(m,1H),1.86-1.71(m,4H),1.60-1.46(m,2H), 1.47(s,6H), 1.38(s,3H), 1.36(s,6H),1.30(s , 3H), 1.04 (s, 6H); MS 516 [M+H] + .
式E-14的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：A cucurbitacin E derivative of formula E-14, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ16.77(s，1H)，7.01(d，J＝12Hz，1H)，6.29(d，J＝12Hz，1H)，5.71(s，1H)，5.51(t，J＝8.4Hz，1H)，5.01(t，2H)，3.65-3.6(m，2H)，3.32-3.23(m，2H)，2.85(m，1H)，2.29-2.27(m，3H)，2.16(m，1H)，1.86-1.71(m，6H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.36(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 518[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 16.77 (s, 1H), 7.01 (d, J = 12 Hz, 1H), 6.29 (d, J = 12 Hz, 1H), 5.71 (s, 1H), 5.51 ( t, J = 8.4 Hz, 1H), 5.01 (t, 2H), 3.65-3.6 (m, 2H), 3.32-3.23 (m, 2H), 2.85 (m, 1H), 2.29-2.27 (m, 3H) , 2.16(m,1H),1.86-1.71(m,6H),1.60-1.46(m,2H), 1.47(s,6H), 1.38(s,3H), 1.36(s,6H),1.30(s , 3H), 1.04 (s, 6H); MS 518 [M+H] + .
式E-15的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：A cucurbitacin E derivative of formula E-15, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ16.35(s，1H)，7.01(d，J＝12Hz，1H)，6.29(d，J＝12Hz，1H)，5.71(s，1H)，5.37(t，J＝8.4Hz，1H)，5.13(m，2H)，5.03(m，1H)，4.08(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，2.85(m，1H)，2.27-2.02(m，5H)，1.85-1.69(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.31(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 678[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 16.35 (s, 1H), 7.01 (d, J = 12 Hz, 1H), 6.29 (d, J = 12 Hz, 1H), 5.71 (s, 1H), 5.37 ( t, J = 8.4 Hz, 1H), 5.13 (m, 2H), 5.03 (m, 1H), 4.08 (m, 1H), 3.79-3.49 (m, 5H), 3.40 (m, 1H), 2.85 (m) , 1H), 2.27-2.02 (m, 5H), 1.85-1.69 (m, 4H), 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.31 (s, 6H) ), 1.30 (s, 3H), 1.04 (s, 6H); MS 678 [M+H] + .
式E-16的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula E-16, which is characterized by NMR techniques to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ15.82(s，1H)，5.71(s，1H)，5.35(t，J＝8.4Hz， 1H)，5，09(b，2H)，5.03(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，3.23(m，1H)，2.85(m，1H)，2.29-2.27(m，7H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.36(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 680[M+H] +。 1 H-NMR (400MHz, CDCl 3 ) δ 15.82 (s, 1H), 5.71 (s, 1H), 5.35 (t, J = 8.4 Hz, 1H), 5, 09 (b, 2H), 5.03 (m) , 1H), 3.79-3.49 (m, 5H), 3.40 (m, 1H), 3.23 (m, 1H), 2.85 (m, 1H), 2.29-2.27 (m, 7H), 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 4H), 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.36 (s, 6H), 1.30 ( s, 3H), 1.04 (s, 6H); MS 680 [M+H] + .
式E-17的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula E-17, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ5.37(t，J＝8.4Hz，1H)，5.08(b，2H)，5.03(m，1H)，4.08(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，2.85(m，1H)，2.27-2.02(m，10H)，1.85-1.69(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.31(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 570[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 5.37 (t, J = 8.4 Hz, 1H), 5.08 (b, 2H), 5.03 (m, 1H), 4.08 (m, 1H), 3.79 - 3.49 (m) , 5H), 3.40 (m, 1H), 2.85 (m, 1H), 2.27-2.02 (m, 10H), 1.85-1.69 (m, 4H), 1.60-1.46 (m, 2H), 1.47 (s, 6H) ), 1.38 (s, 3H), 1.31 (s, 6H), 1.30 (s, 3H), 1.04 (s, 6H); MS 570 [M+H] + .
式E-18的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula E-18, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.66(s，1H)，6.29(d，J＝12Hz，1H)，5.51(t，J＝8.4Hz，1H)，5.03(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，3.23(m，1H)，2.85(m，1H)，2.29-2.27(m，6H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.36(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 584[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.66 (s, 1H), 6.29 (d, J = 12 Hz, 1H), 5.51 (t, J = 8.4 Hz, 1H), 5.03 (m, 1H), 3.79-3.49 (m, 5H), 3.40 (m, 1H), 3.23 (m, 1H), 2.85 (m, 1H), 2.29-2.27 (m, 6H), 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 4H), 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.36 (s , 6H), 1.30 (s, 3H), 1.04 (s, 6H); MS 584 [M+H] + .
式E-19的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula E-19, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.66(s，1H)，6.29(d，J＝12Hz，1H)，5.51(t，J＝8.4Hz，1H)，5.03(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，3.23(m，1H)，2.85(m，1H)，2.29-2.27(m，6H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.36(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 572[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.66 (s, 1H), 6.29 (d, J = 12 Hz, 1H), 5.51 (t, J = 8.4 Hz, 1H), 5.03 (m, 1H), 3.79-3.49 (m, 5H), 3.40 (m, 1H), 3.23 (m, 1H), 2.85 (m, 1H), 2.29-2.27 (m, 6H), 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 4H), 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.36 (s , 6H), 1.30 (s, 3H), 1.04 (s, 6H); MS 572 [M+H] + .
式E-20的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula E-20, which is characterized by NMR techniques to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.66(s，1H)，6.29(d，J＝12Hz，1H)，5.51(t，J＝8.4Hz，1H)，5.03(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，3.23(m，1H)，2.85(m，1H)，2.29-2.27(m，6H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.36(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 586[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.66 (s, 1H), 6.29 (d, J = 12 Hz, 1H), 5.51 (t, J = 8.4 Hz, 1H), 5.03 (m, 1H), 3.79-3.49 (m, 5H), 3.40 (m, 1H), 3.23 (m, 1H), 2.85 (m, 1H), 2.29-2.27 (m, 6H), 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 4H), 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.36 (s , 6H), 1.30 (s, 3H), 1.04 (s, 6H); MS 586 [M+H] + .
式E-21的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula E-21, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.29(d，J＝12Hz，1H)，5.51(t，J＝8.4Hz，1H)，5.03(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，3.23(m，1H)，2.85(m，1H)，2.29-2.27(m，6H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.36(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 718[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.29 (d, J = 12 Hz, 1H), 5.51 (t, J = 8.4 Hz, 1H), 5.03 (m, 1H), 3.79-3.49 (m, 5H), 3.40 (m, 1H), 3.23 (m, 1H), 2.85 (m, 1H), 2.29-2.27 (m, 6H), 2.16 (m, 1H), 2.04 -2.02(m,2H),1.86-1.71(m,4H),1.60-1.46(m,2H), 1.47(s,6H), 1.38(s,3H), 1.36(s,6H),1.30(s , 3H), 1.04 (s, 6H); MS 718 [M+H] + .
式E-22的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：A cucurbitacin E derivative of formula E-22, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.66(s，1H)，6.29(d，J＝12Hz，1H)，5.51(t，J＝8.4Hz，1H)，5.03(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，3.23(m，1H)，2.85(m，1H)，2.29-2.27(m，6H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.36(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 720[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.66 (s, 1H), 6.29 (d, J = 12 Hz, 1H), 5.51 (t, J = 8.4 Hz, 1H), 5.03 (m, 1H), 3.79-3.49 (m, 5H), 3.40 (m, 1H), 3.23 (m, 1H), 2.85 (m, 1H), 2.29-2.27 (m, 6H), 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 4H), 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.36 (s , 6H), 1.30 (s, 3H), 1.04 (s, 6H); MS 720 [M+H] + .
式E-23的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：A cucurbitacin E derivative of formula E-23, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.66(s，1H)，6.29(d，J＝12Hz，1H)，5.51(t，J＝8.4Hz，1H)，5.03(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，3.23(m，1H)，2.85(m，1H)，2.29-2.27(m，6H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.36(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 514[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.66 (s, 1H), 6.29 (d, J = 12 Hz, 1H), 5.51 (t, J = 8.4 Hz, 1H), 5.03 (m, 1H), 3.79-3.49 (m, 5H), 3.40 (m, 1H), 3.23 (m, 1H), 2.85 (m, 1H), 2.29-2.27 (m, 6H), 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 4H), 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.36 (s , 6H), 1.30 (s, 3H), 1.04 (s, 6H); MS 514 [M+H] + .
式E-24的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula E-24, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.29(d，J＝12Hz，1H)，5.37(t，J＝8.4Hz，1H)，5.11(b，2H)，3.65-3.58(m，3H)，3.44(m，1H)，3.23(m，1H)，2.71(m，1H)，2.29-2.27(m，3H)，2.16(m，1H)，1.86-1.71(m，8H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.31(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 516[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.29 (d, J = 12 Hz, 1H), 5.37 (t, J = 8.4 Hz, 1H), 5.11 (b, 2H), 3.65-3.58 (m, 3H), 3.44 (m, 1H), 3.23 (m, 1H), 2.71 (m, 1H), 2.29-2.27 (m, 3H), 2.16 (m, 1H), 1.86 -1.71 (m, 8H), 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.31 (s, 6H), 1.30 (s, 3H), 1.04 (s, 6H) ); MS 516 [M+H] + .
式E-25的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula E-25, which is characterized by NMR techniques to determine the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.66(s，1H)，6.29(d， J＝12Hz，1H)，5.51(t，J＝8.4Hz，1H)，5.03(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，3.23(m，1H)，2.85(m，1H)，2.29-2.27(m，6H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.36(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 676[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.66 (s, 1H), 6.29 (d, J = 12 Hz, 1H), 5.51 (t, J = 8.4 Hz, 1H), 5.03 (m, 1H), 3.79-3.49 (m, 5H), 3.40 (m, 1H), 3.23 (m, 1H), 2.85 (m, 1H), 2.29-2.27 (m, 6H), 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 4H), 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.36 (s , 6H), 1.30 (s, 3H), 1.04 (s, 6H); MS 676 [M+H] + .
式E-26的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula E-26, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.66(s，1H)，6.29(d，J＝12Hz，1H)，5.51(t，J＝8.4Hz，1H)，5.03(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，3.23(m，1H)，2.85(m，1H)，2.29-2.27(m，6H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.36(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 678[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.66 (s, 1H), 6.29 (d, J = 12 Hz, 1H), 5.51 (t, J = 8.4 Hz, 1H), 5.03 (m, 1H), 3.79-3.49 (m, 5H), 3.40 (m, 1H), 3.23 (m, 1H), 2.85 (m, 1H), 2.29-2.27 (m, 6H), 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 4H), 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.36 (s , 6H), 1.30 (s, 3H), 1.04 (s, 6H); MS 678 [M+H] + .
式B-1的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula B-1, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.29(d，J＝12Hz，1H)，5.51(t，J＝8.4Hz，1H)，4.08(m，1H)，3.23(m，1H)，2.29-2.27(m，3H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，6H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.31(s，6H)，1.30(s，3H)，1.14(t，J＝8.4，3H)，1.04(s，6H)；MS 573[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.29 (d, J = 12 Hz, 1H), 5.51 (t, J = 8.4 Hz, 1H), 4.08 (m, 1H), 3.23 (m, 1H), 2.29-2.27 (m, 3H), 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 6H), 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.31 (s, 6H), 1.30 (s, 3H), 1.14 (t, J = 8.4, 3H), 1.04 (s, 6H); 573[M+H] + .
式B-2的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula B-2, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.29(d，J＝12Hz，1H)，5.51(t，J＝8.4Hz，1H)，4.08(m，1H)，3.23(m，1H)，2.29-2.27(m，3H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，8H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.31(s，6H)，1.30(s，3H)，1.04(s，6H)，0.9(t，J＝8.4，3H)；MS 587[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.29 (d, J = 12 Hz, 1H), 5.51 (t, J = 8.4 Hz, 1H), 4.08 (m, 1H), 3.23 (m, 1H), 2.29-2.27 (m, 3H), 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 8H), 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.31 (s, 6H), 1.30 (s, 3H), 1.04 (s, 6H), 0.9 (t, J = 8.4, 3H); 587[M+H] + .
式B-5的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula B-5, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.29(d，J＝12Hz，1H)，5.51(t，J＝8.4Hz，1H)，5.03(m，1H)，4.08(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，2.85(m，1H)，2.27-2.02(m，8H)，1.85-1.69(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.31(s，6H)，1.30(s，3H)，1.04(s，6H)； MS 721[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.29 (d, J = 12 Hz, 1H), 5.51 (t, J = 8.4 Hz, 1H), 5.03 (m, 1H), 4.08 (m, 1H), 3.79-3.49 (m, 5H), 3.40 (m, 1H), 2.85 (m, 1H), 2.27-2.02 (m, 8H), 1.85-1.69 (m, 4H) , 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.31 (s, 6H), 1.30 (s, 3H), 1.04 (s, 6H); MS 721 [M+ H] + .
式B-7的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula B-7, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ5.37(t，J＝8.4Hz，1H)，4.91(m，2H)，3.63-3.55(m，3H)，3.44(m，1H)，3.23(m，1H)，2.29-2.27(m，3H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，12H)，1.60-1.46(m，2H)，1.43(s，6H)，1.38(s，3H)，1.25(s，6H)，1.30(s，3H)，1.14(t，J＝8.4，3H)，1.04(s，6H)；MS 576[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 5.37 (t, J = 8.4 Hz, 1H), 4.91 (m, 2H), 3.63-3.55 (m, 3H), 3.44 (m, 1H), 3.23 (m) , 1H), 2.29-2.27 (m, 3H), 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 12H), 1.60-1.46 (m, 2H), 1.43 (s ,6H), 1.38 (s, 3H), 1.25 (s, 6H), 1.30 (s, 3H), 1.14 (t, J = 8.4, 3H), 1.04 (s, 6H); MS 576 [M+H] + .
式B-8的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula B-8, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.29(d，J＝12Hz，1H)，5.37(t，J＝8.4Hz，1H)，5.11(b，2H)，3.65-3.58(m，3H)，3.44(m，1H)，3.23(m，1H)，2.71(m，1H)，2.29-2.27(m，3H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，8H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.31(s，6H)，1.30(s，3H)，1.14(t，J＝8.4，3H)，1.04(s，6H)；MS 588[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.29 (d, J = 12 Hz, 1H), 5.37 (t, J = 8.4 Hz, 1H), 5.11 (b, 2H), 3.65-3.58 (m, 3H), 3.44 (m, 1H), 3.23 (m, 1H), 2.71 (m, 1H), 2.29-2.27 (m, 3H), 2.16 (m, 1H), 2.04 -2.02(m,2H),1.86-1.71(m,8H),1.60-1.46(m,2H), 1.47(s,6H), 1.38(s,3H),1.31(s,6H),1.30(s , 3H), 1.14 (t, J = 8.4, 3H), 1.04 (s, 6H); MS 588 [M+H] + .
式B-9的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula B-9, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ5.37(t，J＝8.4Hz，1H)，4.91(m，2H)，3.63-3.55(m，3H)，3.44(m，1H)，3.23(m，1H)，2.29-2.27(m，3H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，12H)，1.60-1.46(m，2H)，1.43(s，6H)，1.38(s，3H)，1.25(s，6H)，1.30(s，3H)，1.14(t，J＝8.4，3H)，1.04(s，6H)；MS 576[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 5.37 (t, J = 8.4 Hz, 1H), 4.91 (m, 2H), 3.63-3.55 (m, 3H), 3.44 (m, 1H), 3.23 (m) , 1H), 2.29-2.27 (m, 3H), 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 12H), 1.60-1.46 (m, 2H), 1.43 (s ,6H), 1.38 (s, 3H), 1.25 (s, 6H), 1.30 (s, 3H), 1.14 (t, J = 8.4, 3H), 1.04 (s, 6H); MS 576 [M+H] + .
式B-10的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：A cucurbitacin E derivative of formula B-10, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ5.37(t，J＝8.4Hz，1H)，4.91(m，2H)，3.63-3.55(m，3H)，3.44(m，1H)，3.23(m，1H)，2.29-2.27(m，3H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，14H)，1.60-1.46(m，2H)，1.43(s，6H)，1.38(s，3H)，1.25(s，6H)，1.30(s，3H)，1.14(t，J＝8.4，3H)，1.04(s，6H)；MS 590[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 5.37 (t, J = 8.4 Hz, 1H), 4.91 (m, 2H), 3.63-3.55 (m, 3H), 3.44 (m, 1H), 3.23 (m) , 1H), 2.29-2.27 (m, 3H), 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 14H), 1.60-1.46 (m, 2H), 1.43 (s , 6H), 1.38 (s, 3H), 1.25 (s, 6H), 1.30 (s, 3H), 1.14 (t, J = 8.4, 3H), 1.04 (s, 6H); MS 590 [M+H] + .
式B-11的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula B-11, which is characterized by nuclear magnetic resonance spectroscopy and its mass spectrometry:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.29(d，J＝12Hz，1H)，5.37(t，J＝8.4Hz，1H)，5.13(m，2H)，5.03(m，1H)，4.08(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，2.85(m，1H)，2.27-2.02(m，8H)，1.85-1.69(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.31(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 722[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.29 (d, J = 12 Hz, 1H), 5.37 (t, J = 8.4 Hz, 1H), 5.13 (m, 2H), 5.03 (m, 1H), 4.08 (m, 1H), 3.79-3.49 (m, 5H), 3.40 (m, 1H), 2.85 (m, 1H), 2.27-2.02 (m, 8H), 1.85 -1.69 (m, 4H), 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.31 (s, 6H), 1.30 (s, 3H), 1.04 (s, 6H) ); MS 722 [M+H] + .
式B-12的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula B-12, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ5.37(t，J＝8.4Hz，1H)，5.08(b，2H)，5.03(m，1H)，4.08(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，2.85(m，1H)，2.27-2.02(m，12H)，1.85-1.69(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.31(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 724[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 5.37 (t, J = 8.4 Hz, 1H), 5.08 (b, 2H), 5.03 (m, 1H), 4.08 (m, 1H), 3.79 - 3.49 (m) , 5H), 3.40 (m, 1H), 2.85 (m, 1H), 2.27-2.02 (m, 12H), 1.85-1.69 (m, 4H), 1.60-1.46 (m, 2H), 1.47 (s, 6H) ), 1.38 (s, 3H), 1.31 (s, 6H), 1.30 (s, 3H), 1.04 (s, 6H); MS 724 [M+H] + .
式B-13的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula B-13, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.29(d，J＝12Hz，1H)，5.37(t，J＝8.4Hz，1H)，5.11(b，2H)，3.65-3.58(m，3H)，3.44(m，1H)，3.23(m，1H)，2.71(m，1H)，2.29-2.27(m，3H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.31(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 518[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.29 (d, J = 12 Hz, 1H), 5.37 (t, J = 8.4 Hz, 1H), 5.11 (b, 2H), 3.65-3.58 (m, 3H), 3.44 (m, 1H), 3.23 (m, 1H), 2.71 (m, 1H), 2.29-2.27 (m, 3H), 2.16 (m, 1H), 2.04 -2.02(m,2H),1.86-1.71(m,4H),1.60-1.46(m,2H), 1.47(s,6H), 1.38(s,3H),1.31(s,6H),1.30(s , 3H), 1.04 (s, 6H); MS 518 [M+H] + .
式B-14的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula B-14, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.29(d，J＝12Hz，1H)，5.37(t，J＝8.4Hz，1H)，5.11(b，2H)，3.65-3.58(m，3H)，3.44(m，1H)，3.23(m，1H)，2.71(m，1H)，2.29-2.27(m，3H)，2.16(m，1H)，1.86-1.71(m，8H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.31(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 520[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.29 (d, J = 12 Hz, 1H), 5.37 (t, J = 8.4 Hz, 1H), 5.11 (b, 2H), 3.65-3.58 (m, 3H), 3.44 (m, 1H), 3.23 (m, 1H), 2.71 (m, 1H), 2.29-2.27 (m, 3H), 2.16 (m, 1H), 1.86 -1.71 (m, 8H), 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.31 (s, 6H), 1.30 (s, 3H), 1.04 (s, 6H) ); MS 520 [M+H] + .
式B-15的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula B-15, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.29(d，J＝12Hz，1H)，5.37(t，J＝8.4Hz，1H)，5.13(m，2H)，5.03(m，1H)，4.08(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，2.85(m，1H)，2.27-2.02(m，5H)，1.85-1.69(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.31(s，6H)，1.30(s，3H)，1.04(s，6H)； MS 681[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.29 (d, J = 12 Hz, 1H), 5.37 (t, J = 8.4 Hz, 1H), 5.13 (m, 2H), 5.03 (m, 1H), 4.08 (m, 1H), 3.79-3.49 (m, 5H), 3.40 (m, 1H), 2.85 (m, 1H), 2.27-2.02 (m, 5H), 1.85 -1.69 (m, 4H), 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.31 (s, 6H), 1.30 (s, 3H), 1.04 (s, 6H) ); MS 681 [M+H] + .
式B-16的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula B-16, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ5.37(t，J＝8.4Hz，1H)，5.08(b，2H)，5.03(m，1H)，4.08(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，2.85(m，1H)，2.27-2.02(m，10H)，1.85-1.69(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.31(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 683[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 5.37 (t, J = 8.4 Hz, 1H), 5.08 (b, 2H), 5.03 (m, 1H), 4.08 (m, 1H), 3.79 - 3.49 (m) , 5H), 3.40 (m, 1H), 2.85 (m, 1H), 2.27-2.02 (m, 10H), 1.85-1.69 (m, 4H), 1.60-1.46 (m, 2H), 1.47 (s, 6H) ), 1.38 (s, 3H), 1.31 (s, 6H), 1.30 (s, 3H), 1.04 (s, 6H); MS 683 [M+H] + .
式B-17的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula B-17, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.66(s，1H)，6.29(d，J＝12Hz，1H)，5.51(t，J＝8.4Hz，1H)，5.03(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，3.23(m，1H)，2.85(m，1H)，2.29-2.27(m，6H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.36(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 572[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.66 (s, 1H), 6.29 (d, J = 12 Hz, 1H), 5.51 (t, J = 8.4 Hz, 1H), 5.03 (m, 1H), 3.79-3.49 (m, 5H), 3.40 (m, 1H), 3.23 (m, 1H), 2.85 (m, 1H), 2.29-2.27 (m, 6H), 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 4H), 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.36 (s , 6H), 1.30 (s, 3H), 1.04 (s, 6H); MS 572 [M+H] + .
式B-18的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula B-18, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.66(s，1H)，6.29(d，J＝12Hz，1H)，5.51(t，J＝8.4Hz，1H)，5.03(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，3.23(m，1H)，2.85(m，1H)，2.29-2.27(m，6H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.36(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 586[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.66 (s, 1H), 6.29 (d, J = 12 Hz, 1H), 5.51 (t, J = 8.4 Hz, 1H), 5.03 (m, 1H), 3.79-3.49 (m, 5H), 3.40 (m, 1H), 3.23 (m, 1H), 2.85 (m, 1H), 2.29-2.27 (m, 6H), 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 4H), 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.36 (s , 6H), 1.30 (s, 3H), 1.04 (s, 6H); MS 586 [M+H] + .
式B-19的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula B-19, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.66(s，1H)，6.29(d，J＝12Hz，1H)，5.51(t，J＝8.4Hz，1H)，5.03(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，3.23(m，1H)，2.85(m，1H)，2.29-2.27(m，6H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.36(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 574[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.66 (s, 1H), 6.29 (d, J = 12 Hz, 1H), 5.51 (t, J = 8.4 Hz, 1H), 5.03 (m, 1H), 3.79-3.49 (m, 5H), 3.40 (m, 1H), 3.23 (m, 1H), 2.85 (m, 1H), 2.29-2.27 (m, 6H), 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 4H), 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.36 (s , 6H), 1.30 (s, 3H), 1.04 (s, 6H); MS 574 [M+H] + .
式B-20的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula B-20, which is characterized by nuclear magnetic resonance spectroscopy and its mass spectrometry:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.66(s，1H)，6.29(d， J＝12Hz，1H)，5.51(t，J＝8.4Hz，1H)，5.03(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，3.23(m，1H)，2.85(m，1H)，2.29-2.27(m，6H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.36(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 588[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.66 (s, 1H), 6.29 (d, J = 12 Hz, 1H), 5.51 (t, J = 8.4 Hz, 1H), 5.03 (m, 1H), 3.79-3.49 (m, 5H), 3.40 (m, 1H), 3.23 (m, 1H), 2.85 (m, 1H), 2.29-2.27 (m, 6H), 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 4H), 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.36 (s , 6H), 1.30 (s, 3H), 1.04 (s, 6H); MS 588 [M+H] + .
式B-21的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula B-21, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.66(s，1H)，6.29(d，J＝12Hz，1H)，5.51(t，J＝8.4Hz，1H)，5.03(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，3.23(m，1H)，2.85(m，1H)，2.29-2.27(m，6H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.36(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 720[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.66 (s, 1H), 6.29 (d, J = 12 Hz, 1H), 5.51 (t, J = 8.4 Hz, 1H), 5.03 (m, 1H), 3.79-3.49 (m, 5H), 3.40 (m, 1H), 3.23 (m, 1H), 2.85 (m, 1H), 2.29-2.27 (m, 6H), 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 4H), 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.36 (s , 6H), 1.30 (s, 3H), 1.04 (s, 6H); MS 720 [M+H] + .
式B-22的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula B-22, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.66(s，1H)，6.29(d，J＝12Hz，1H)，5.51(t，J＝8.4Hz，1H)，5.03(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，3.23(m，1H)，2.85(m，1H)，2.29-2.27(m，6H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.36(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 722[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.66 (s, 1H), 6.29 (d, J = 12 Hz, 1H), 5.51 (t, J = 8.4 Hz, 1H), 5.03 (m, 1H), 3.79-3.49 (m, 5H), 3.40 (m, 1H), 3.23 (m, 1H), 2.85 (m, 1H), 2.29-2.27 (m, 6H), 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 4H), 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.36 (s , 6H), 1.30 (s, 3H), 1.04 (s, 6H); MS 722 [M+H] + .
式B-23的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula B-23, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.66(s，1H)，6.29(d，J＝12Hz，1H)，5.51(t，J＝8.4Hz，1H)，5.03(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，3.23(m，1H)，2.85(m，1H)，2.29-2.27(m，6H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.36(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 516[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.66 (s, 1H), 6.29 (d, J = 12 Hz, 1H), 5.51 (t, J = 8.4 Hz, 1H), 5.03 (m, 1H), 3.79-3.49 (m, 5H), 3.40 (m, 1H), 3.23 (m, 1H), 2.85 (m, 1H), 2.29-2.27 (m, 6H), 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 4H), 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.36 (s , 6H), 1.30 (s, 3H), 1.04 (s, 6H); MS 516 [M+H] + .
式B-24的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula B-24, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.66(s，1H)，6.29(d，J＝12Hz，1H)，5.51(t，J＝8.4Hz，1H)，5.03(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，3.23(m，1H)，2.85(m，1H)，2.29-2.27(m，6H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.36(s， 6H)，1.30(s，3H)，1.04(s，6H)；MS 518[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.66 (s, 1H), 6.29 (d, J = 12 Hz, 1H), 5.51 (t, J = 8.4 Hz, 1H), 5.03 (m, 1H), 3.79-3.49 (m, 5H), 3.40 (m, 1H), 3.23 (m, 1H), 2.85 (m, 1H), 2.29-2.27 (m, 6H), 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 4H), 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.36 (s , 6H), 1.30 (s, 3H), 1.04 (s, 6H); MS 518 [M+H] + .
式B-25的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula B-25, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.29(d，J＝12Hz，1H)，5.32(t，J＝8.4Hz，1H)，5.15(b，2H)，5.03(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，3.23(m，1H)，2.85(m，1H)，2.29-2.27(m，6H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.36(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 678[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.29 (d, J = 12 Hz, 1H), 5.32 (t, J = 8.4 Hz, 1H), 5.15 (b, 2H), 5.03 (m, 1H), 3.79-3.49 (m, 5H), 3.40 (m, 1H), 3.23 (m, 1H), 2.85 (m, 1H), 2.29-2.27 (m, 6H), 2.16 (m, 1H), 2.04-2.02 (m, 2H), 1.86-1.71 (m, 4H), 1.60-1.46 (m, 2H), 1.47 (s, 6H), 1.38 (s, 3H), 1.36 (s , 6H), 1.30 (s, 3H), 1.04 (s, 6H); MS 678 [M+H] + .
式B-26的葫芦素E衍生物，通过核磁共振技术阐明其结构和质谱计算化合物分子量：The cucurbitacin E derivative of formula B-26, which is characterized by nuclear magnetic resonance to elucidate its structure and mass spectrometry to calculate the molecular weight of the compound:
1H-NMR(400MHz，CDCl 3)δ7.01(d，J＝12Hz，1H)，6.29(d，J＝12Hz，1H)，5.36(t，J＝8.4Hz，1H)，5.03(m，1H)，3.79-3.49(m，5H)，3.40(m，1H)，3.23(m，1H)，2.85(m，1H)，2.29-2.27(m，6H)，2.16(m，1H)，2.04-2.02(m，2H)，1.86-1.71(m，4H)，1.60-1.46(m，2H)，1.47(s，6H)，1.38(s，3H)，1.36(s，6H)，1.30(s，3H)，1.04(s，6H)；MS 680[M+H] +。 1 H-NMR (400 MHz, CDCl 3 ) δ 7.01 (d, J = 12 Hz, 1H), 6.29 (d, J = 12 Hz, 1H), 5.36 (t, J = 8.4 Hz, 1H), 5.03 (m, 1H), 3.79-3.49 (m, 5H), 3.40 (m, 1H), 3.23 (m, 1H), 2.85 (m, 1H), 2.29-2.27 (m, 6H), 2.16 (m, 1H), 2.04 -2.02(m,2H),1.86-1.71(m,4H),1.60-1.46(m,2H), 1.47(s,6H), 1.38(s,3H), 1.36(s,6H),1.30(s , 3H), 1.04 (s, 6H); MS 680 [M+H] + .
化合物式E-7、式E-8、式E-9、式E-10与式B-7、式B-8、式B-9、式B-10的合成路线如下图：The synthetic route of the compound formula E-7, formula E-8, formula E-9, formula E-10 and formula B-7, formula B-8, formula B-9 and formula B-10 is as follows:
Figure PCTCN2018117201-appb-000006
Figure PCTCN2018117201-appb-000006
其中，式E-1、式E-2、式B-1、式B-2结构式如下：Wherein, the structural formulas of the formula E-1, the formula E-2, the formula B-1, and the formula B-2 are as follows:
Figure PCTCN2018117201-appb-000007
Figure PCTCN2018117201-appb-000007
化合物式E-11、式E-12与式B-11、式B-12的合成路线如下图：The synthetic route of the compound formula E-11, formula E-12 and formula B-11 and formula B-12 is as follows:
Figure PCTCN2018117201-appb-000008
Figure PCTCN2018117201-appb-000008
其中，式E-5、式B-5结构式如下：Among them, the structural formula of E-5 and B-5 is as follows:
Figure PCTCN2018117201-appb-000009
Figure PCTCN2018117201-appb-000009
化合物式E-13、式E-14与式B-13、式B-14的合成路线如下图：The synthetic route of the compound formula E-13, formula E-14 and formula B-13 and formula B-14 is as follows:
Figure PCTCN2018117201-appb-000010
Figure PCTCN2018117201-appb-000010
化合物式B-15、式B-16、式E-15、式E-16分别由式B-11、式B-12、式E-11、式E-12经氢氧化锂水解而得。The compound B-15, the formula B-16, the formula E-15 and the formula E-16 are obtained by hydrolyzing lithium hydroxide of the formula B-11, the formula B-12, the formula E-11 and the formula E-12, respectively.
化合物式E-17、式E-18、式E-19、式E-20、式E-23的合成路线如下图：The synthetic route of the compound formula E-17, formula E-18, formula E-19, formula E-20, and formula E-23 is as follows:
Figure PCTCN2018117201-appb-000011
Figure PCTCN2018117201-appb-000011
上式中的合成条件：a)对甲苯磺酰氯，DABCO，二氯甲烷，0℃；b)叠氮钠，DMF，70℃；c)氢氧化锂，甲醇，室温；d)丙酰氯或丁酰氯，二氯甲烷，吡啶，0℃至室温；e)10％钯碳，氢气，乙醇。The synthesis conditions in the above formula: a) p-toluenesulfonyl chloride, DABCO, dichloromethane, 0 ° C; b) sodium azide, DMF, 70 ° C; c) lithium hydroxide, methanol, room temperature; d) propionyl chloride or butyl Acid chloride, dichloromethane, pyridine, 0 ° C to room temperature; e) 10% palladium on carbon, hydrogen, ethanol.
化合物式B-17、式B-18、式B-19、式B-20、式B-23分别由式E-17、式E-18、式E-19、式E-20、式E-23还原而得，式E-24由式E-23催化加氢还原而得，式B-24由式E-24还原而得。The compound formula B-17, formula B-18, formula B-19, formula B-20, and formula B-23 are respectively from formula E-17, formula E-18, formula E-19, formula E-20, formula E- 23 is obtained by reduction, and the formula E-24 is obtained by catalytic hydrogenation reduction of the formula E-23, and the formula B-24 is obtained by reduction of the formula E-24.
化合物式E-21、式E-22的合成路线如下图：The synthetic route of the compound formula E-21 and formula E-22 is as follows:
Figure PCTCN2018117201-appb-000012
Figure PCTCN2018117201-appb-000012
上式中化合物式E-21-01的合成同式B-5-1。The synthesis of the compound of the formula E-21-01 in the above formula is the same as the formula B-5-1.
化合物式E-25、式E-26分别由式E-21、式E-22水解得到，化合物式B-21、式B-22、式B-25、式B-26分别由化合物式E-21、式E-22、式E-25、式E-26还原而得。The compound of the formula E-25 and the formula E-26 are respectively obtained by hydrolysis of the formula E-21 and the formula E-22, and the compound of the formula B-21, the formula B-22, the formula B-25 and the formula B-26 are respectively obtained from the compound formula E- 21. Formula E-22, E-25, and E-26 are obtained by reduction.
新发现的上述20种葫芦素B衍生物与20种葫芦素E衍生物以及它们的盐，由于分别与葫芦素B、葫芦素E具有共同的基本结构，所以性质也基本与葫芦素B、葫芦素E一样，具有较好的抗癌、抗病毒、抗炎症和保肝脏作用，而且毒副作用较低。The newly discovered 20 kinds of cucurbitacin B derivatives and 20 kinds of cucurbitacin E derivatives and their salts have the same basic structure with cucurbitacin B and cucurbitacin E respectively, so the properties are basically the same with cucurbitacin B and gourd. Like E, it has good anti-cancer, anti-viral, anti-inflammatory and liver-protecting effects, and has low toxic side effects.
具体实施方式Detailed ways
下面结合具体的实施例对本申请做进一步详细的说明，但本申请不限于以下实施例。The present application will be further described in detail below with reference to specific embodiments, but the application is not limited to the following embodiments.
实施例一化合物的制备Preparation of the compound of Example 1
1、B-1-1的合成：将葫芦素B(559毫克，1.0毫摩尔)溶解在10毫升甲醇中，然后加入1N的氢氧化锂水溶液(1毫升)，室温搅拌2小时，浓缩，残余物以二氯甲烷溶解，以碱水洗涤，有机层干燥浓缩，得502毫克白色固体，收率97.2％。1. Synthesis of B-1-1: Dissolve cucurbitacin B (559 mg, 1.0 mmol) in 10 ml of methanol, then add 1N aqueous lithium hydroxide solution (1 ml), stir at room temperature for 2 hours, concentrate, residue The product was dissolved in dichloromethane, washed with EtOAc EtOAc (EtOAc)
2、B-1的合成：将化合物B-1-1(51.6毫克，0.1毫摩尔)溶解在10毫升二氯甲烷中，然后加入吡啶(10毫克)，再加入丙酰氯(10毫克)，室温反应2小时，反应完毕，反应液以酸水洗涤，有机层干燥浓缩，残余物柱层析纯化得到42毫克白色固体，收率74％。2. Synthesis of B-1: Compound B-1-1 (51.6 mg, 0.1 mmol) was dissolved in 10 ml of dichloromethane, then pyridine (10 mg) was added, followed by propionyl chloride (10 mg), room temperature After reacting for 2 hours, the reaction was completed, the reaction mixture was washed with aqueous acid, and the organic layer was dried and concentrated, and the residue was purified by column chromatography.
3、B-7的合成：将化合物B-1(57.3毫克，0.1毫摩尔)溶解在10毫升甲醇中，然后加入氨甲醇溶液(4摩尔/升，3毫升)，室温搅拌半小时后，加入三乙酰氧基硼氢化钠(64毫克，0.3毫摩尔)，继续搅拌4小时，反应完毕，浓缩，将残余物分散于二氯甲烷与水中，水层再以二氯甲烷提取一次，合并有机层，无水硫酸钠干燥，过滤，浓缩，柱层析纯化，得到52.3毫克白色固体，收率91％。3. Synthesis of B-7: Compound B-1 (57.3 mg, 0.1 mmol) was dissolved in 10 ml of methanol, then added with ammonia methanol solution (4 mol/L, 3 ml), stirred at room temperature for half an hour, and then added. Sodium triacetoxyborohydride (64 mg, 0.3 mmol), stirring was continued for 4 hours, the reaction was completed, concentrated, and the residue was taken from dichloromethane and water. The organic layer was dried over anhydrous sodium sulfate, filtered, and evaporated.
4、B-9的合成：将化合物B-7(57.4毫克)溶解在10毫升乙醇中，然后加入0.3克10％的钯碳，氮气置换，然后氢气置换，保持2atm压力，搅拌反应1小时，过滤，浓缩，得57.6毫克白色固体，收率100％。4. Synthesis of B-9: Compound B-7 (57.4 mg) was dissolved in 10 ml of ethanol, then 0.3 g of 10% palladium carbon was added, replaced with nitrogen, then replaced with hydrogen, maintained at a pressure of 2 atm, and stirred for 1 hour. Filtration and concentration gave 57.6 mg of a white solid.
5、E-1-1的合成：将葫芦素E(557毫克，1.0毫摩尔)溶解在10毫升甲醇中，然后加入1N的氢氧化锂水溶液(1毫升)，室温搅拌2小时，浓缩，残余物以二氯甲烷溶解，以碱水洗涤，有机层干燥浓缩，得498毫克白色固体， 收率96.8％。5. Synthesis of E-1-1: Dissolve cucurbitacin E (557 mg, 1.0 mmol) in 10 ml of methanol, then add 1N aqueous lithium hydroxide solution (1 ml), stir at room temperature for 2 hours, concentrate, residue The product was dissolved in dichloromethane, washed with EtOAc (EtOAc)EtOAc.
6、E-1的合成：将化合物E-1-1(51.4毫克，0.1毫摩尔)溶解在10毫升二氯甲烷中，然后加入吡啶(10毫克)，再加入丙酰氯(10毫克)，室温反应2小时，反应完毕，反应液以酸水洗涤，有机层干燥浓缩，残余物柱层析纯化得到47毫克白色固体，收率83％。6. Synthesis of E-1: Compound E-1-1 (51.4 mg, 0.1 mmol) was dissolved in 10 ml of dichloromethane, then pyridine (10 mg) was added followed by propionyl chloride (10 mg) at room temperature. After reacting for 2 hours, the reaction was completed, the reaction mixture was washed with aqueous acid, and the organic layer was dried and concentrated, and the residue was purified by column chromatography to yield 47 mg of white solid.
7、E-7的合成：将化合物E-1(57毫克，0.1毫摩尔)溶解在10毫升甲醇中，然后加入氨甲醇溶液(4摩尔/升，3毫升)，室温搅拌半小时后，加入三乙酰氧基硼氢化钠(64毫克，0.3毫摩尔)，继续搅拌4小时，反应完毕，浓缩，将残余物分散于二氯甲烷与水中，水层再以二氯甲烷提取一次，合并有机层，无水硫酸钠干燥，过滤，浓缩，柱层析纯化，得到51.5毫克白色固体，收率90％。7. Synthesis of E-7: Compound E-1 (57 mg, 0.1 mmol) was dissolved in 10 ml of methanol, then added with ammonia methanol solution (4 mol/L, 3 ml), stirred at room temperature for half an hour, and then added. Sodium triacetoxyborohydride (64 mg, 0.3 mmol), stirring was continued for 4 hours, the reaction was completed, concentrated, and the residue was taken from dichloromethane and water. Drying over anhydrous sodium sulfate, filtration, concentration and purification by column chromatography to give 51.5 mg of white solid.
8、E-9的合成：将化合物B-7(57.4毫克)溶解在10毫升乙醇中，然后加入0.3克10％的钯碳，氮气置换，然后氢气置换，保持2atm压力，搅拌反应1小时，过滤，浓缩，得57.6毫克白色固体，收率100％。8. Synthesis of E-9: Compound B-7 (57.4 mg) was dissolved in 10 ml of ethanol, then 0.3 g of 10% palladium carbon was added, replaced with nitrogen, then replaced with hydrogen, maintained at a pressure of 2 atm, and stirred for 1 hour. Filtration and concentration gave 57.6 mg of a white solid.
9、B-2的合成：将化合物B-1-1(51.6毫克，0.1毫摩尔)溶解在10毫升二氯甲烷中，然后加入吡啶(10毫克)，再加入丁酰氯(10毫克)，室温反应2小时，反应完毕，反应液以酸水洗涤，有机层干燥浓缩，残余物柱层析纯化得到45毫克白色固体，收率77％。9. Synthesis of B-2: Compound B-1-1 (51.6 mg, 0.1 mmol) was dissolved in 10 ml of dichloromethane, then pyridine (10 mg) was added, then butyryl chloride (10 mg) was added at room temperature. After reacting for 2 hours, the reaction was completed, the reaction mixture was washed with aqueous acid, and the organic layer was dried and concentrated, and the residue was purified by column chromatography to afford 45 mg of white solid.
10、B-8的合成：将化合物B-2(57.3毫克，0.1毫摩尔)溶解在10毫升甲醇中，然后加入氨甲醇溶液(4摩尔/升，3毫升)，室温搅拌半小时后，加入三乙酰氧基硼氢化钠(64毫克，0.3毫摩尔)，继续搅拌4小时，反应完毕，浓缩，将残余物分散于二氯甲烷与水中，水层再以二氯甲烷提取一次，合并有机层，无水硫酸钠干燥，过滤，浓缩，柱层析纯化，得到52.3毫克白色固体，收率91％。10. Synthesis of B-8: Compound B-2 (57.3 mg, 0.1 mmol) was dissolved in 10 ml of methanol, then added with ammonia methanol solution (4 mol/L, 3 ml), stirred at room temperature for half an hour, and then added. Sodium triacetoxyborohydride (64 mg, 0.3 mmol), stirring was continued for 4 hours, the reaction was completed, concentrated, and the residue was taken from dichloromethane and water. The organic layer was dried over anhydrous sodium sulfate, filtered, and evaporated.
11、B-10的合成：将化合物B-8(58.7毫克)溶解在10毫升乙醇中，然后加入0.3克10％的钯碳，氮气置换，然后氢气置换，保持2atm压力，搅拌反应1小时，过滤，浓缩，得58.9毫克白色固体，收率100％。11. Synthesis of B-10: Compound B-8 (58.7 mg) was dissolved in 10 ml of ethanol, then 0.3 g of 10% palladium carbon was added, replaced with nitrogen, then replaced with hydrogen, maintained at a pressure of 2 atm, and stirred for 1 hour. Filtration and concentration gave 58.9 mg of a white solid.
12、E-2的合成：将化合物E-1-1(51.4毫克，0.1毫摩尔)溶解在10毫升二氯甲烷中，然后加入吡啶(10毫克)，再加入丁酰氯(11毫克)，室温反应2小时，反应完毕，反应液以酸水洗涤，有机层干燥浓缩，残余物柱层析纯化得到50毫克白色固体，收率86％。12. Synthesis of E-2: Compound E-1-1 (51.4 mg, 0.1 mmol) was dissolved in 10 ml of dichloromethane, then pyridine (10 mg) was added, then butyryl chloride (11 mg) was added at room temperature. After reacting for 2 hours, the reaction was completed, the reaction mixture was washed with aqueous acid, and the organic layer was dried and concentrated, and the residue was purified by column chromatography to afford 50 mg of white solid.
13、E-8的合成：将化合物E-2(58.4毫克，0.1毫摩尔)溶解在10毫升甲醇中，然后加入氨甲醇溶液(4摩尔/升，3毫升)，室温搅拌半小时后，加入三乙酰氧基硼氢化钠(64毫克，0.3毫摩尔)，继续搅拌4小时，反应完毕，浓缩，将残余物分散于二氯甲烷与水中，水层再以二氯甲烷提取一次，合并有机层，无水硫酸钠干燥，过滤，浓缩，柱层析纯化，得到56.3毫克白色固体。13. Synthesis of E-8: Compound E-2 (58.4 mg, 0.1 mmol) was dissolved in 10 ml of methanol, then an ammonia methanol solution (4 mol/L, 3 ml) was added, and stirred at room temperature for half an hour, then added. Sodium triacetoxyborohydride (64 mg, 0.3 mmol), stirring was continued for 4 hours, the reaction was completed, concentrated, and the residue was taken from dichloromethane and water. Dry over anhydrous sodium sulfate, filtered, concentrated and purified elut
14、E-10的合成：将化合物E-7(57.4毫克)溶解在10毫升乙醇中，然后加入0.3克10％的钯碳，氮气置换，然后氢气置换，保持2atm压力，搅拌反应1小时，过滤，浓缩，得57.6毫克白色固体。14. Synthesis of E-10: Compound E-7 (57.4 mg) was dissolved in 10 ml of ethanol, then 0.3 g of 10% palladium carbon was added, replaced with nitrogen, then replaced with hydrogen, maintained at a pressure of 2 atm, and stirred for 1 hour. Filtration and concentration gave 57.6 mg of a white solid.
15、G-1的合成：将葡萄糖(1.8克，10毫摩尔)溶解在20毫升丙酮中，然后加入1，1-二甲氧基丙烷(2.1克，20毫摩尔)以及硫酸(1滴)，室温搅拌1小时，浓缩至尽，残余物以乙酸乙酯溶解，以水洗涤，有机层干燥浓缩，得到2.13克无色油状物，收率82％。15. Synthesis of G-1: Glucose (1.8 g, 10 mmol) was dissolved in 20 ml of acetone, then 1,1-dimethoxypropane (2.1 g, 20 mmol) and sulfuric acid (1 drop) were added. The mixture was stirred at room temperature for 1 hr. EtOAc was evaporated.
16、B-5-1的合成：将葫芦素B(559毫克，1毫摩尔)、G-1(260毫克，1毫摩尔)、氧化锌(81.5毫克，1毫摩尔)溶解在10毫升甲醇中，室温搅拌一小时，浓缩至尽，残余物以乙酸乙酯溶解，以饱和盐水洗涤，有机层干燥浓缩，剩余物以柱层析纯化，得到624毫克白色固体，收率78％。16. Synthesis of B-5-1: Dissolve cucurbitacin B (559 mg, 1 mmol), G-1 (260 mg, 1 mmol), zinc oxide (81.5 mg, 1 mmol) in 10 ml of methanol The mixture was stirred at room temperature for 1 hr. EtOAc was evaporated.
17、B-5的合成：将化合物B-5-1(400毫克，0.5毫摩尔)溶解在10毫升甲苯中，然后加入对甲苯磺酸(86毫克，0.5毫摩尔)，室温搅拌18小时，反应完毕，往反应液中加入饱和碳酸氢钠水溶液洗涤，有机层干燥浓缩，残余物以柱层析纯化，得到248毫克白色固体，收率69％。17. Synthesis of B-5: Compound B-5-1 (400 mg, 0.5 mmol) was dissolved in 10 ml of toluene, then p-toluenesulfonic acid (86 mg, 0.5 mmol) was added and stirred at room temperature for 18 hours. After the reaction was completed, a saturated aqueous solution of sodium hydrogencarbonate was added, and the organic layer was dried and evaporated.
18、B-11的合成：将化合物B-5(72毫克，0.1毫摩尔)溶解在10毫升甲醇中，然后加入氨甲醇溶液(4摩尔/升，3毫升)，室温搅拌半小时后，加入三乙酰氧基硼氢化钠(64毫克，0.3毫摩尔)，继续搅拌4小时，反应完毕，浓缩，将残余物分散于二氯甲烷与水中，水层再以二氯甲烷提取一次，合并有机层，无水硫酸钠干燥，过滤，浓缩，柱层析纯化，得到64毫克白色固体。18. Synthesis of B-11: Compound B-5 (72 mg, 0.1 mmol) was dissolved in 10 ml of methanol, then added with ammonia methanol solution (4 mol/L, 3 ml), stirred at room temperature for half an hour, and then added. Sodium triacetoxyborohydride (64 mg, 0.3 mmol), stirring was continued for 4 hours, the reaction was completed, concentrated, and the residue was taken from dichloromethane and water. Dry over anhydrous sodium sulfate, filtered, concentrated and purified elut
19、B-12的合成：将化合物B-11(72.1毫克)溶解在10毫升乙醇中，然后加入0.3克10％的钯碳，氮气置换，然后氢气置换，保持2atm压力，搅拌反应1小时，过滤，浓缩，得72.3毫克白色固体。19. Synthesis of B-12: Compound B-11 (72.1 mg) was dissolved in 10 ml of ethanol, then 0.3 g of 10% palladium carbon was added, replaced with nitrogen, then replaced with hydrogen, maintained at a pressure of 2 atm, and stirred for 1 hour. Filtration and concentration gave 72.3 mg of a white solid.
20、E-5-1的合成：将葫芦素E(556毫克，1毫摩尔)、G-1(260毫克，1毫摩尔)、氧化锌(81.5毫克，1毫摩尔)溶解在10毫升甲醇中，室温搅拌一小时，浓缩至尽，残余物以乙酸乙酯溶解，以饱和盐水洗涤，有机层干燥浓 缩，剩余物以柱层析纯化，得到606毫克白色固体，收率76％。20. Synthesis of E-5-1: cucurbitacin E (556 mg, 1 mmol), G-1 (260 mg, 1 mmol), zinc oxide (81.5 mg, 1 mmol) dissolved in 10 ml of methanol The mixture was stirred at room temperature for 1 hr. EtOAc was evaporated.
21、E-5的合成：将化合物E-5-1(400毫克，0.5毫摩尔)溶解在10毫升甲苯中，然后加入对甲苯磺酸(86毫克，0.5毫摩尔)，室温搅拌18小时，反应完毕，往反应液中加入饱和碳酸氢钠水溶液洗涤，有机层干燥浓缩，残余物以柱层析纯化，得到240毫克白色固体，收率67％。21, Synthesis of E-5: Compound E-5-1 (400 mg, 0.5 mmol) was dissolved in 10 ml of toluene, then p-toluenesulfonic acid (86 mg, 0.5 mmol) was added and stirred at room temperature for 18 hours. After the reaction was completed, a saturated aqueous solution of sodium hydrogencarbonate was added, and the organic layer was dried and evaporated.
22、E-11的合成：将化合物E-5(72毫克，0.1毫摩尔)溶解在10毫升甲醇中，然后加入氨甲醇溶液(4摩尔/升，3毫升)，室温搅拌半小时后，加入三乙酰氧基硼氢化钠(64毫克，0.3毫摩尔)，继续搅拌4小时，反应完毕，浓缩，将残余物分散于二氯甲烷与水中，水层再以二氯甲烷提取一次，合并有机层，无水硫酸钠干燥，过滤，浓缩，柱层析纯化，得到65毫克白色固体，收率92％。22. Synthesis of E-11: Compound E-5 (72 mg, 0.1 mmol) was dissolved in 10 ml of methanol, then an ammonia methanol solution (4 mol/L, 3 ml) was added, and stirred at room temperature for half an hour, then added. Sodium triacetoxyborohydride (64 mg, 0.3 mmol), stirring was continued for 4 hours, the reaction was completed, concentrated, and the residue was taken from dichloromethane and water. Drying over anhydrous sodium sulfate, filtration, concentration and purification by column chromatography to give 65 mg of white solid.
23、E-12的合成：将化合物E-11(72毫克)溶解在10毫升乙醇中，然后加入0.3克10％的钯碳，氮气置换，然后氢气置换，保持2atm压力，搅拌反应1小时，过滤，浓缩，得69.8毫克白色固体，收率97％。23. Synthesis of E-12: Compound E-11 (72 mg) was dissolved in 10 ml of ethanol, then 0.3 g of 10% palladium carbon was added, replaced with nitrogen, then replaced with hydrogen, maintained at a pressure of 2 atm, and stirred for 1 hour. Filtration and concentration gave 69.8 mg of a white solid.
24、B-13的合成：将化合物B-1-1(57.3毫克，0.1毫摩尔)溶解在10毫升甲醇中，然后加入氨甲醇溶液(4摩尔/升，3毫升)，室温搅拌半小时后，加入三乙酰氧基硼氢化钠(64毫克，0.3毫摩尔)，继续搅拌4小时，反应完毕，浓缩，将残余物分散于二氯甲烷与水中，水层再以二氯甲烷提取一次，合并有机层，无水硫酸钠干燥，过滤，浓缩，柱层析纯化，得到52.3毫克白色固体，收率91％。24. Synthesis of B-13: Compound B-1-1 (57.3 mg, 0.1 mmol) was dissolved in 10 ml of methanol, then a solution of ammonia (4 mol/L, 3 ml) was added and stirred at room temperature for half an hour. Add sodium triacetoxyborohydride (64 mg, 0.3 mmol), stir for 4 hours, complete the reaction, concentrate, disperse the residue in dichloromethane and water. The organic layer was dried with anhydrous sodium sulfate, filtered, evaporated,
25、B-14的合成：将化合物B-13(52毫克)溶解在10毫升乙醇中，然后加入0.3克10％的钯碳，氮气置换，然后氢气置换，保持2atm压力，搅拌反应1小时，过滤，浓缩，得52毫克白色固体，收率100％。25. Synthesis of B-14: Compound B-13 (52 mg) was dissolved in 10 ml of ethanol, then 0.3 g of 10% palladium carbon was added, replaced with nitrogen, then replaced with hydrogen, maintained at a pressure of 2 atm, and stirred for 1 hour. Filtration and concentration gave 52 mg of a white solid.
26、E-13的合成：将化合物E-1-1(0.1毫摩尔)溶解在10毫升甲醇中，然后加入氨甲醇溶液(4摩尔/升，3毫升)，室温搅拌半小时后，加入三乙酰氧基硼氢化钠(64毫克，0.3毫摩尔)，继续搅拌4小时，反应完毕，浓缩，将残余物分散于二氯甲烷与水中，水层再以二氯甲烷提取一次，合并有机层，无水硫酸钠干燥，过滤，浓缩，柱层析纯化，得到52.3毫克白色固体。26. Synthesis of E-13: Compound E-1-1 (0.1 mmol) was dissolved in 10 ml of methanol, then added with ammonia methanol solution (4 mol/L, 3 ml), stirred at room temperature for half an hour, and then added three. Sodium acetoxyborohydride (64 mg, 0.3 mmol) was stirred for 4 hours. The reaction was completed and concentrated. The residue was crystallised from dichloromethane and water. Dry over anhydrous sodium sulfate, filtered, EtOAc EtOAcqqq
27、E-14的合成：将化合物E-13(51.5毫克)溶解在10毫升乙醇中，然后加入0.3克10％的钯碳，氮气置换，然后氢气置换，保持2atm压力，搅拌反应1小时，过滤，浓缩，得57.6毫克白色固体，收率100％。27. Synthesis of E-14: Compound E-13 (51.5 mg) was dissolved in 10 ml of ethanol, then 0.3 g of 10% palladium carbon was added, replaced with nitrogen, then replaced with hydrogen, maintained at a pressure of 2 atm, and stirred for 1 hour. Filtration and concentration gave 57.6 mg of a white solid.
28、B-15的合成：将B-11(73毫克，0.1毫摩尔)溶解于5甲醇中，然后加入1N氢氧化锂水溶液(100微升，0.1毫摩尔)，室温搅拌1小时后，反应完毕，浓缩除去甲醇，残余物分散于二氯甲烷与水中，二氯甲烷层干燥，过滤，浓缩，得到67毫克白色固体，收率98.5％。28. Synthesis of B-15: B-11 (73 mg, 0.1 mmol) was dissolved in 5 methanol, then 1N aqueous lithium hydroxide solution (100 μL, 0.1 mmol) was added, and the mixture was stirred at room temperature for 1 hour. After completion, the residue was evaporated to dichloromethane.
29、B-16的合成：将B-12(73毫克，0.1毫摩尔)溶解于5甲醇中，然后加入1N氢氧化锂水溶液(100微升，0.1毫摩尔)，室温搅拌1小时后，反应完毕，浓缩除去甲醇，残余物分散于二氯甲烷与水中，二氯甲烷层干燥，过滤，浓缩，得到67毫克白色固体，收率98.5％。29. Synthesis of B-16: B-12 (73 mg, 0.1 mmol) was dissolved in 5 methanol, then 1N aqueous lithium hydroxide solution (100 μL, 0.1 mmol) was added, and the mixture was stirred at room temperature for 1 hour. After completion, the residue was evaporated to dichloromethane.
30、E-15的合成：将E-11(73毫克，0.1毫摩尔)溶解于5甲醇中，然后加入1N氢氧化锂水溶液(100微升，0.1毫摩尔)，室温搅拌1小时后，反应完毕，浓缩除去甲醇，残余物分散于二氯甲烷与水中，二氯甲烷层干燥，过滤，浓缩，得到67毫克白色固体，收率98.5％。30. Synthesis of E-15: E-11 (73 mg, 0.1 mmol) was dissolved in 5 methanol, then 1N aqueous lithium hydroxide solution (100 μL, 0.1 mmol) was added and stirred at room temperature for 1 hour. After completion, the residue was evaporated to dichloromethane.
31、E-16的合成：将E-12(73毫克，0.1毫摩尔)溶解于5甲醇中，然后加入1N氢氧化锂水溶液(100微升，0.1毫摩尔)，室温搅拌1小时后，反应完毕，浓缩除去甲醇，残余物分散于二氯甲烷与水中，二氯甲烷层干燥，过滤，浓缩，得到67毫克白色固体，收率98.5％。31, E-16 synthesis: E-12 (73 mg, 0.1 mmol) was dissolved in 5 methanol, then 1N aqueous lithium hydroxide solution (100 μL, 0.1 mmol), stirred at room temperature for 1 hour, the reaction After completion, the residue was evaporated to dichloromethane.
32、E-17的合成：将化合物E-23(51.6毫克，0.1毫摩尔)溶解在10毫升二氯甲烷中，然后加入吡啶(10毫克)，再加入丙酰氯(10毫克)，室温反应2小时，反应完毕，反应液以酸水洗涤，有机层干燥浓缩，残余物柱层析纯化得到42毫克白色固体，收率74％。32. Synthesis of E-17: Compound E-23 (51.6 mg, 0.1 mmol) was dissolved in 10 ml of dichloromethane, then pyridine (10 mg) was added, then propionyl chloride (10 mg) was added and reacted at room temperature 2 After the reaction was completed, the reaction mixture was washed with EtOAc.
33、E-18的合成：将化合物E-23(51.6毫克，0.1毫摩尔)溶解在10毫升二氯甲烷中，然后加入吡啶(10毫克)，再加入丁酰氯(10毫克)，室温反应2小时，反应完毕，反应液以酸水洗涤，有机层干燥浓缩，残余物柱层析纯化得到42毫克白色固体，收率74％。33. Synthesis of E-18: Compound E-23 (51.6 mg, 0.1 mmol) was dissolved in 10 ml of dichloromethane, then pyridine (10 mg) was added, then butyryl chloride (10 mg) was added and reacted at room temperature 2 After the reaction was completed, the reaction mixture was washed with EtOAc.
34、E-19的合成：将化合物E-17(57.4毫克)溶解在10毫升乙醇中，然后加入0.3克10％的钯碳，氮气置换，然后氢气置换，保持2atm压力，搅拌反应1小时，过滤，浓缩，得57.6毫克白色固体，收率100％。34. Synthesis of E-19: Compound E-17 (57.4 mg) was dissolved in 10 ml of ethanol, then 0.3 g of 10% palladium carbon was added, replaced with nitrogen, then replaced with hydrogen, maintained at a pressure of 2 atm, and stirred for 1 hour. Filtration and concentration gave 57.6 mg of a white solid.
35、E-20的合成：将化合物E-18(57.4毫克)溶解在10毫升乙醇中，然后加入0.3克10％的钯碳，氮气置换，然后氢气置换，保持2atm压力，搅拌反应1小时，过滤，浓缩，得57.6毫克白色固体，收率100％。35. Synthesis of E-20: Compound E-18 (57.4 mg) was dissolved in 10 ml of ethanol, then 0.3 g of 10% palladium carbon was added, replaced with nitrogen, then replaced with hydrogen, maintained at a pressure of 2 atm, and stirred for 1 hour. Filtration and concentration gave 57.6 mg of a white solid.
36、B-17的合成：将化合物E-17溶解在甲醇中，然后加入氰基硼氢化钠， 室温搅拌6小时，反应完毕后，浓缩，残余物分散于水和二氯甲烷中，二氯甲烷层干燥，过滤，浓缩，柱层析，得到目标产物B-17，呈白色固体状。36. Synthesis of B-17: Compound E-17 was dissolved in methanol, then sodium cyanoborohydride was added, and stirred at room temperature for 6 hours. After completion of the reaction, concentration was carried out, and the residue was dispersed in water and dichloromethane. The methane layer was dried, filtered, concentrated, and purified eluted elute
37、B-18的合成：将化合物E-18溶解在甲醇中，然后加入氰基硼氢化钠，室温搅拌6小时，反应完毕后，浓缩，残余物分散于水和二氯甲烷中，二氯甲烷层干燥，过滤，浓缩，柱层析，得到目标产物B-18，呈白色固体状。37. Synthesis of B-18: Compound E-18 was dissolved in methanol, then sodium cyanoborohydride was added, and stirred at room temperature for 6 hours. After completion of the reaction, concentration was carried out, and the residue was dispersed in water and dichloromethane. The methane layer was dried, filtered, concentrated, and purified tolululu
38、B-19的合成：将化合物E-19溶解在甲醇中，然后加入氰基硼氢化钠，室温搅拌6小时，反应完毕后，浓缩，残余物分散于水和二氯甲烷中，二氯甲烷层干燥，过滤，浓缩，柱层析，得到目标产物B-19，呈白色固体状。38. Synthesis of B-19: Compound E-19 was dissolved in methanol, then sodium cyanoborohydride was added, and stirred at room temperature for 6 hours. After completion of the reaction, concentration was carried out, and the residue was dispersed in water and dichloromethane. The methane layer was dried, filtered, concentrated, and then purified to afford white crystals.
39、B-20的合成：将化合物E-20溶解在甲醇中，然后加入氰基硼氢化钠，室温搅拌6小时，反应完毕后，浓缩，残余物分散于水和二氯甲烷中，二氯甲烷层干燥，过滤，浓缩，柱层析，得到目标产物B-20，呈白色固体状。39. Synthesis of B-20: Compound E-20 was dissolved in methanol, then sodium cyanoborohydride was added, and stirred at room temperature for 6 hours. After completion of the reaction, concentration was carried out, and the residue was dispersed in water and dichloromethane. The methane layer was dried, filtered, concentrated, and purified tolululu
40、E-23的合成：将E-23-02溶解在甲醇中，然后加入1N的氢氧化锂水溶液，室温搅拌2小时，浓缩，残余物以二氯甲烷溶解，以碱水洗涤，有机层干燥浓缩，得白色固体为E-23。40, E-23 synthesis: E-23-02 was dissolved in methanol, then added 1N aqueous lithium hydroxide solution, stirred at room temperature for 2 hours, concentrated, the residue was dissolved in dichloromethane, washed with alkaline water, organic layer Dry and concentrated to give a white solid as E-23.
41、E-24的合成：将化合物E-23(57.4毫克)溶解在10毫升乙醇中，然后加入0.3克10％的钯碳，氮气置换，然后氢气置换，保持2atm压力，搅拌反应1小时，过滤，浓缩，得57.6毫克白色固体，收率100％。41. Synthesis of E-24: Compound E-23 (57.4 mg) was dissolved in 10 ml of ethanol, then 0.3 g of 10% palladium carbon was added, replaced with nitrogen, then replaced with hydrogen, maintained at a pressure of 2 atm, and stirred for 1 hour. Filtration and concentration gave 57.6 mg of a white solid.
42、B-23的合成：将化合物E-23溶解在甲醇中，然后加入氰基硼氢化钠，室温搅拌6小时，反应完毕后，浓缩，残余物分散于水和二氯甲烷中，二氯甲烷层干燥，过滤，浓缩，柱层析，得到目标产物B-23，呈白色固体状。42. Synthesis of B-23: Compound E-23 was dissolved in methanol, then sodium cyanoborohydride was added, and stirred at room temperature for 6 hours. After completion of the reaction, concentration was carried out, and the residue was dispersed in water and dichloromethane. The methane layer was dried, filtered, concentrated, and purified tolululu
43、B-24的合成：将化合物E-24溶解在甲醇中，然后加入氰基硼氢化钠，室温搅拌6小时，反应完毕后，浓缩，残余物分散于水和二氯甲烷中，二氯甲烷层干燥，过滤，浓缩，柱层析，得到目标产物B-24，呈白色固体状。43. Synthesis of B-24: Compound E-24 was dissolved in methanol, then sodium cyanoborohydride was added, and stirred at room temperature for 6 hours. After completion of the reaction, concentration was carried out, and the residue was dispersed in water and dichloromethane. The methane layer was dried, filtered, concentrated, and purified eluted elute
44、E-21的合成：将化合物E-21-01(400毫克，0.5毫摩尔)溶解在10毫升甲苯中，然后加入对甲苯磺酸(86毫克，0.5毫摩尔)，室温搅拌18小时，反应完毕，往反应液中加入饱和碳酸氢钠水溶液洗涤，有机层干燥浓缩，残余物以柱层析纯化，得到248毫克白色固体，收率69％。Synthesis of E-21: Compound E-21-01 (400 mg, 0.5 mmol) was dissolved in 10 ml of toluene, then p-toluenesulfonic acid (86 mg, 0.5 mmol) was added and stirred at room temperature for 18 hours. After the reaction was completed, a saturated aqueous solution of sodium hydrogencarbonate was added, and the organic layer was dried and evaporated.
45、E-22的合成：将化合物E-21(57.4毫克)溶解在10毫升乙醇中，然后加入0.3克10％的钯碳，氮气置换，然后氢气置换，保持2atm压力，搅拌反应1小时，过滤，浓缩，得57.6毫克白色固体，收率100％。45. Synthesis of E-22: Compound E-21 (57.4 mg) was dissolved in 10 ml of ethanol, then 0.3 g of 10% palladium carbon was added, replaced with nitrogen, then replaced with hydrogen, maintained at a pressure of 2 atm, and stirred for 1 hour. Filtration and concentration gave 57.6 mg of a white solid.
46、E-25的合成：将E-21(559毫克，1.0毫摩尔)溶解在10毫升甲醇 中，然后加入1N的氢氧化锂水溶液(1毫升)，室温搅拌2小时，浓缩，残余物以二氯甲烷溶解，以碱水洗涤，有机层干燥浓缩，得502毫克白色固体，收率97.2％。46. Synthesis of E-25: E-21 (559 mg, 1.0 mmol) was dissolved in 10 ml of methanol, then 1N aqueous lithium hydroxide (1 ml), and stirred at room temperature for 2 hr. Dichloromethane was dissolved, washed with aqueous alkali and the organic layer was dried and concentrated to yield 502 g of white solid.
47、E-26的合成：将E-22(559毫克，1.0毫摩尔)溶解在10毫升甲醇中，然后加入1N的氢氧化锂水溶液(1毫升)，室温搅拌2小时，浓缩，残余物以二氯甲烷溶解，以碱水洗涤，有机层干燥浓缩，得502毫克白色固体，收率97.2％。47. Synthesis of E-26: E-22 (559 mg, 1.0 mmol) was dissolved in 10 ml of methanol, then 1N aqueous lithium hydroxide (1 ml) was added and stirred at room temperature for 2 hr. Dichloromethane was dissolved, washed with aqueous alkali and the organic layer was dried and concentrated to yield 502 g of white solid.
48、B-21的合成：将化合物E-21溶解在甲醇中，然后加入氰基硼氢化钠，室温搅拌6小时，反应完毕后，浓缩，残余物分散于水和二氯甲烷中，二氯甲烷层干燥，过滤，浓缩，柱层析，得到目标产物B-21，呈白色固体状。48. Synthesis of B-21: Compound E-21 was dissolved in methanol, then sodium cyanoborohydride was added, and stirred at room temperature for 6 hours. After completion of the reaction, concentration was carried out, and the residue was dispersed in water and dichloromethane. The methane layer was dried, filtered, concentrated, and purified eluted elute
49、B-22的合成：将化合物E-22溶解在甲醇中，然后加入氰基硼氢化钠，室温搅拌6小时，反应完毕后，浓缩，残余物分散于水和二氯甲烷中，二氯甲烷层干燥，过滤，浓缩，柱层析，得到目标产物B-22，呈白色固体状。49. Synthesis of B-22: Compound E-22 was dissolved in methanol, then sodium cyanoborohydride was added, and stirred at room temperature for 6 hours. After completion of the reaction, concentration was carried out, and the residue was dispersed in water and dichloromethane. The methane layer was dried, filtered, concentrated, and purified tolululu
50、B-25的合成：将化合物E-25溶解在甲醇中，然后加入氰基硼氢化钠，室温搅拌6小时，反应完毕后，浓缩，残余物分散于水和二氯甲烷中，二氯甲烷层干燥，过滤，浓缩，柱层析，得到目标产物B-25，呈白色固体状。50, B-25 synthesis: the compound E-25 was dissolved in methanol, then sodium cyanoborohydride was added, stirred at room temperature for 6 hours, after the reaction was completed, concentrated, the residue was dispersed in water and dichloromethane, dichloro The methane layer was dried, filtered, concentrated and purified tolululu
51、B-26的合成：将化合物E-26溶解在甲醇中，然后加入氰基硼氢化钠，室温搅拌6小时，反应完毕后，浓缩，残余物分散于水和二氯甲烷中，二氯甲烷层干燥，过滤，浓缩，柱层析，得到目标产物B-26，呈白色固体状。51, B-26 synthesis: the compound E-26 was dissolved in methanol, then added sodium cyanoborohydride, stirred at room temperature for 6 hours, after the reaction was completed, concentrated, the residue was dispersed in water and dichloromethane, dichloro The methane layer was dried, filtered, concentrated, and purified tolululu
实施例二Embodiment 2
人的血管内皮细胞系(HUVEC)细胞在添加有不同浓度的葫芦素E或葫芦素E衍生物并同时含有浓度为10nM的人重组血管内皮细胞生长生因子培养液中培养8个小时，对培养后的细胞进行处理，检测HUVEC细胞内STAT3磷酸化活性，结果如下：Human vascular endothelial cell line (HUVEC) cells were cultured for 8 hours in human recombinant vascular endothelial growth factor culture medium supplemented with different concentrations of cucurbitacin E or cucurbitacin E derivative and containing 10 nM at the same time. The cells were treated to detect STAT3 phosphorylation activity in HUVEC cells. The results were as follows:
表1 葫芦素E衍生物对STAT3磷酸化酶的活性的抑制作用的检测结果Table 1 Test results of inhibition of STAT3 phosphorylase activity by cucurbitacin E derivatives
化合物Compound 抑制STAT3磷酸化酶活性IC50(nM)Inhibition of STAT3 phosphorylase activity IC50 (nM)
葫芦素ECucurbitacin E 11
葫芦素E衍生物B-7Cucurbitacin E derivative B-7 0.20.2
葫芦素E衍生物B-8Cucurbitacin E derivative B-8 0.50.5
葫芦素E衍生物B-9Cucurbitacin E derivative B-9 0.70.7
葫芦素E衍生物B-10Cucurbitacin E derivative B-10 0.40.4
葫芦素E衍生物B-11Cucurbitacin E derivative B-11 0.60.6
葫芦素E衍生物B-12Cucurbitacin E derivative B-12 0.80.8
葫芦素E衍生物B-13Cucurbitacin E derivative B-13 0.40.4
葫芦素E衍生物B-14Cucurbitacin E derivative B-14 1.31.3
葫芦素E衍生物B-15Cucurbitacin E derivative B-15 0.50.5
葫芦素E衍生物B-16Cucurbitacin E derivative B-16 0.70.7
葫芦素E衍生物B-17Cucurbitacin E derivative B-17 0.40.4
葫芦素E衍生物B-18Cucurbitacin E derivative B-18 0.60.6
葫芦素E衍生物B-19Cucurbitacin E derivative B-19 0.20.2
葫芦素E衍生物B-20Cucurbitacin E derivative B-20 0.10.1
葫芦素E衍生物B-21Cucurbitacin E derivative B-21 1.51.5
葫芦素E衍生物B-22Cucurbitacin E derivative B-22 0.90.9
葫芦素E衍生物B-23Cucurbitacin E derivative B-23 5.45.4
葫芦素E衍生物B-24Cucurbitacin E derivative B-24 0.50.5
葫芦素E衍生物B-25Cucurbitacin E derivative B-25 0.80.8
葫芦素E衍生物B-26Cucurbitacin E derivative B-26 0.10.1
葫芦素E衍生物E-7Cucurbitacin E derivative E-7 7.97.9
葫芦素E衍生物E-8Cucurbitacin E derivative E-8 0.80.8
葫芦素E衍生物E-9Cucurbitacin E derivative E-9 0.30.3
葫芦素E衍生物E-10Cucurbitacin E derivative E-10 0.60.6
葫芦素E衍生物E-11Cucurbitacin E derivative E-11 0.70.7
葫芦素E衍生物E-12Cucurbitacin E derivative E-12 0.50.5
葫芦素E衍生物E-13Cucurbitacin E derivative E-13 5.45.4
葫芦素E衍生物E-14Cucurbitacin E derivative E-14 0.90.9
葫芦素E衍生物E-15Cucurbitacin E derivative E-15 0.30.3
葫芦素E衍生物E-16Cucurbitacin E derivative E-16 0.70.7
葫芦素E衍生物E-17Cucurbitacin E derivative E-17 0.40.4
葫芦素E衍生物E-18Cucurbitacin E derivative E-18 2.32.3
葫芦素E衍生物E-19Cucurbitacin E derivative E-19 0.70.7
葫芦素E衍生物E-20Cucurbitacin E derivative E-20 0.60.6
葫芦素E衍生物E-21Cucurbitacin E derivative E-21 0.40.4
葫芦素E衍生物E-22Cucurbitacin E derivative E-22 10.110.1
葫芦素E衍生物E-23Cucurbitacin E derivative E-23 0.20.2
葫芦素E衍生物E-24Cucurbitacin E derivative E-24 0.40.4
葫芦素E衍生物E-25Cucurbitacin E derivative E-25 0.90.9
葫芦素E衍生物E-26Cucurbitacin E derivative E-26 0.50.5
制得的葫芦素B新衍生物和葫芦素E新衍生物，功能分别与现有的葫芦素B、葫芦素E相同，有抗癌、抗病毒、抗炎症以及保肝的作用。换句话说，研究这些葫芦素B和E新衍生物的药理的方法同现有的葫芦素B、葫芦素E，故在此不赘述，有关现有的葫芦素B和葫芦素E的药理作用报道具体参见下述公开的文献：The new derivative of cucurbitacin B and the new derivative of cucurbitacin E have the same functions as the existing cucurbitacin B and cucurbitacin E, and have anti-cancer, anti-viral, anti-inflammatory and hepatoprotective effects. In other words, the pharmacological methods for studying these new cucurbitacin B and E derivatives are the same as the existing cucurbitacin B and cucurbitacin E, so the pharmacological effects of the existing cucurbitacin B and cucurbitacin E are not described here. The report specifically refers to the documents disclosed below:
1、Geissman，T.A.(1964).“New substances of plant origin”，Annu.Rev.Pharmacol.，4，305-316。1. Geissman, T.A. (1964). "New substances of plant origin", Annu. Rev. Pharmacol., 4, 305-316.
2、方新德.葫芦素类成份的化学与生物活性的研究进展[J].国外医学：药学分册，1985，3：132。2, Fang Xinde. Research progress in the chemical and biological activities of cucurbitacin components [J]. Foreign Medical: Pharmaceutics, 1985, 3:132.
3、Gitter S.et al.Studies on the antitumor effect of cucurbitacins.Cancer Reseach.1961，21：516。3. Gitter S. et al. Studies on the antitumor effect of cucurbitacins. Cancer Reseach. 1961, 21: 516.
4、Gallily R.et al.Further studies on the antitumor effect of cucubitacins.Cance Research.1962，22：1038。4. Gallily R. et al. Vehicle studies on the antitumor effect of cucubitacins. Cance Research. 1962, 22: 1038.
5、韩德五马学惠等.葫芦素B对实验性肝炎与肝硬变的防治作用[J].中华医学杂志，1979，59(4)：208。5, Han De Wu Ma Xuehui et al. Prevention and treatment of cucurbitacin B on experimental hepatitis and cirrhosis [J]. Chinese Medical Journal, 1979, 59 (4): 208.
6、Jian Chao Chen，Ming Hua Chiu，Rui Lin Nie，Geoffrey A.Cordell and Samuel X.Qiu(2005)，″Cucurbitacins and cucurbitane glycosides：structures and biological activities″ Natural Product Reports，volume 22，pages 386-399。6. Jian Chao Chen, Ming Hua Chiu, Rui Lin Nie, Geoffrey A. Cordell and Samuel X. Qiu (2005), "Cucurbitacins and cucurbitane glycosides: structures and biological activities" Natural Product Reports, volume 22, pages 386-399.
7、Chiy-Rong Chen，Yun-Wen Liao，Lai Wang，Yueh-Hsiung Kuo，Hung-Jen Liu，Wen-Ling Shih，Hsueh-Ling Cheng and Chi-I Chang(2010).″Cucurbitane Trit erpenoids from Momordica charantia and Their Cytoprotective Activity in tert-Butyl Hydroperoxide-Induced Hepatotoxicity of HepG2 Cells″.Chemical & pharmaceutical bulletin，volume 58，issue 12，pages 1639-1642。7. Chiy-Rong Chen, Yun-Wen Liao, Lai Wang, Yueh-Hsiung Kuo, Hung-Jen Liu, Wen-Ling Shih, Hsueh-Ling Cheng and Chi-I Chang (2010). "Cucurbitane Trit erpenoids from Momordica charantia And Their Cytoprotective Activity in tert-Butyl Hydroperoxide-Induced Hepatotoxicity of HepG2 Cells". Chemical & pharmaceutical bulletin, volume 58, issue 12, pages 1639-1642.
8、Jian-Chao Chen，Gao-Hong Zhang，Zhong-Quan Zhang，Ming-Hua Qiu，Yong-Tang Zheng，Liu-Meng Yang，Kai-Bei Yu(2008)，″Octanorcucurbitane and Cucurbitane Triterpenoids from the Tubers of Hemsleya endecaphylla with HIV-1 Inhibitory Activity″.J.Nat.Prod.volume 71，pages 153-155。8. Jian-Chao Chen, Gao-Hong Zhang, Zhong-Quan Zhang, Ming-Hua Qiu, Yong-Tang Zheng, Liu-Meng Yang, Kai-Bei Yu (2008), "Octanorcucurbitane and Cucurbitane Triterpenoids from the Tubers of Hemsleya Endecaphylla with HIV-1 Inhibitory Activity". J. Nat. Prod. volume 71, pages 153-155.
9、Da-Cheng Wang，Hong-Yu Pan，Xu-Ming Deng，Hua Xiang，Hui-Yuan Gao， Hui Cai，and Li-Jun Wu(2007)，″Cucurbitane and hexanorcucurbitane glycosides from the fruits of Cucurbita pepo cv dayangua″.Journal of Asian Natural Products Research，volume 9，issue 6，pages 525-529.9. Da-Cheng Wang, Hong-Yu Pan, Xu-Ming Deng, Hua Xiang, Hui-Yuan Gao, Hui Cai, and Li-Jun Wu (2007), "Cucurbitane and hexanorcucurbitane glycosides from the fruits of Cucurbita pepo cv dayangua ".Journal of Asian Natural Products Research, volume 9, issues 6, pages 525-529.
上述实施例只为说明本申请的技术构思及特点，其目的在于让熟悉此项技术的人士能够了解本申请的内容并据以实施，并不能以此限制本申请的保护范围，凡根据本申请精神实质所作的等效变化或修饰，都应涵盖在本申请的保护范围之内。The above embodiments are only for explaining the technical idea and the features of the present application, and the purpose of the present invention is to enable those skilled in the art to understand the contents of the present application and to implement the present application, and the scope of protection of the present application is not limited thereto. Equivalent changes or modifications made to the spirit of the spirit should be covered by the scope of this application.

Claims (11)

  1. 下式表示葫芦素E衍生物，或者其药学上可接受的盐：The following formula represents a cucurbitacin E derivative, or a pharmaceutically acceptable salt thereof:
    Figure PCTCN2018117201-appb-100001
    Figure PCTCN2018117201-appb-100001
    Figure PCTCN2018117201-appb-100002
    Figure PCTCN2018117201-appb-100002
  2. 制备式E-7、式E-8、式E-9或式E-10的葫芦素E衍生物的方法，其特征在于：Process for the preparation of a cucurbitacin E derivative of formula E-7, formula E-8, formula E-9 or formula E-10, characterized in that:
    将葫芦素E溶解在甲醇中，然后加入氢氧化锂水溶液，室温搅拌，浓缩，残余物以二氯甲烷溶解，以碱水洗涤，有机层干燥浓缩，得式E-1-1表示的白 色固体，The cucurbitacin E is dissolved in methanol, and then an aqueous solution of lithium hydroxide is added thereto, stirred at room temperature, concentrated, and the residue is dissolved in dichloromethane, washed with aqueous alkali and dried and concentrated to give a white solid of formula E-1-1. ,
    Figure PCTCN2018117201-appb-100003
    Figure PCTCN2018117201-appb-100003
    将式E-1-1的化合物溶解在二氯甲烷中，然后加入吡啶，再加入丙酰氯，室温反应，反应完毕，反应液以酸水洗涤，有机层干燥浓缩，残余物柱层析纯化得到式E-1表示的白色固体，The compound of the formula E-1-1 is dissolved in dichloromethane, then pyridine is added, then propionyl chloride is added, and the reaction is carried out at room temperature. The reaction is completed, the reaction solution is washed with acid water, the organic layer is dried and concentrated, and the residue is purified by column chromatography. a white solid represented by the formula E-1,
    Figure PCTCN2018117201-appb-100004
    Figure PCTCN2018117201-appb-100004
    将式E-1表示的化合物溶解在甲醇中，然后加入氨甲醇溶液，室温搅拌，加入三乙酰氧基硼氢化钠，继续搅拌，反应完毕，浓缩，将残余物分散于二氯甲烷与水中，水层再以二氯甲烷提取一次，合并有机层，无水硫酸钠干燥，过滤，浓缩，柱层析纯化得到白色固体，即为所述式E-7的葫芦素E的衍生物，The compound represented by the formula E-1 is dissolved in methanol, then added with an ammonia methanol solution, stirred at room temperature, sodium triacetoxyborohydride is added, stirring is continued, the reaction is completed, concentrated, and the residue is dispersed in dichloromethane and water. The aqueous layer is extracted once more with dichloromethane, and the organic layer is combined, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography to obtain a white solid, which is a derivative of the cucurbitin E of the formula E-7,
    Figure PCTCN2018117201-appb-100005
    Figure PCTCN2018117201-appb-100005
    将式E-7的葫芦素E的衍生物溶解在乙醇中，然后加入钯碳，氮气置换，然后氢气置换，保持2atm压力，搅拌反应，过滤，浓缩，得白色固体，即为所述式E-9的葫芦素E的衍生物，The derivative of cucurbitacin E of formula E-7 is dissolved in ethanol, then added with palladium carbon, replaced with nitrogen, then replaced with hydrogen, maintained at a pressure of 2 atm, stirred, filtered, and concentrated to give a white solid. a derivative of cucurbitacin E of -9,
    Figure PCTCN2018117201-appb-100006
    Figure PCTCN2018117201-appb-100006
    或者，式E-1-1的化合物溶解在二氯甲烷中，然后加入吡啶，再加入丁酰氯，室温反应，反应完毕，反应液以酸水洗涤，有机层干燥浓缩，残余物柱层析纯化得到式E-2表示的白色固体，Alternatively, the compound of the formula E-1-1 is dissolved in dichloromethane, then pyridine is added, then butyryl chloride is added, and the reaction is carried out at room temperature. The reaction is completed, the reaction solution is washed with acid water, the organic layer is dried and concentrated, and the residue is purified by column chromatography. A white solid represented by the formula E-2 is obtained,
    Figure PCTCN2018117201-appb-100007
    Figure PCTCN2018117201-appb-100007
    将式E-2表示的化合物溶解在甲醇中，然后加入氨甲醇溶液，室温搅拌后，加入三乙酰氧基硼氢化钠，继续搅拌，反应完毕，浓缩，将残余物分散于二氯甲烷与水中，水层再以二氯甲烷提取一次，合并有机层，无水硫酸钠干燥，过滤，浓缩，柱层析纯化得到白色固体，即为所述式E-8的葫芦素E的衍生物，The compound represented by the formula E-2 is dissolved in methanol, and then an ammonia methanol solution is added. After stirring at room temperature, sodium triacetoxyborohydride is added, stirring is continued, the reaction is completed, and the residue is dispersed in dichloromethane and water. The aqueous layer is extracted once more with dichloromethane, and the organic layer is combined, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography to obtain a white solid, which is a derivative of the cucurbitacin E of the formula E-8,
    Figure PCTCN2018117201-appb-100008
    Figure PCTCN2018117201-appb-100008
    将式E-8的葫芦素E的衍生物溶解在乙醇中，然后加入钯碳，氮气置换，然后氢气置换，保持2atm压力，搅拌反应，过滤，浓缩，得白色固体，即为所述式E-10的葫芦素E的衍生物，The derivative of cucurbitacin E of formula E-8 is dissolved in ethanol, then added with palladium carbon, replaced with nitrogen, then replaced with hydrogen, maintained at a pressure of 2 atm, stirred, filtered, and concentrated to give a white solid. -10 derivatives of cucurbitacin E,
    Figure PCTCN2018117201-appb-100009
    Figure PCTCN2018117201-appb-100009
  3. 制备式E-11、式E-12、式E-15或式E-16的葫芦素E衍生物的方法，其特征在于：Process for the preparation of a cucurbitacin E derivative of formula E-11, formula E-12, formula E-15 or formula E-16, characterized in that:
    将葡萄糖溶解在丙酮中，然后加入1，1-二甲氧基丙烷以及硫酸，室温搅拌，浓缩至尽，残余物用乙酸乙酯溶解，以水洗涤，有机层干燥浓缩，得到式G-1表示的无色油状物，The glucose is dissolved in acetone, then 1,1-dimethoxypropane and sulfuric acid are added, and the mixture is stirred at room temperature, and the residue is concentrated to dryness. a colorless oil,
    Figure PCTCN2018117201-appb-100010
    Figure PCTCN2018117201-appb-100010
    将葫芦素E、式G-1表示的化合物、氧化锌溶解在甲醇中，室温搅拌，浓缩至尽，残余物用乙酸乙酯溶解，以饱和盐水洗涤，有机层干燥浓缩，剩余物以柱层析纯化，得到式E-5-1表示的白色固体，The cucurbitacin E, the compound represented by the formula G-1, and the zinc oxide are dissolved in methanol, stirred at room temperature, and concentrated to the end. The residue is dissolved in ethyl acetate, washed with saturated brine, and then dried and concentrated. Purification to obtain a white solid represented by formula E-5-1.
    Figure PCTCN2018117201-appb-100011
    Figure PCTCN2018117201-appb-100011
    将式E-5-1的化合物溶解在甲苯中，然后加入对甲苯磺酸，室温搅拌，反应完毕，往反应液中加入饱和碳酸氢钠水溶液洗涤，有机层干燥浓缩，残余物以柱层析纯化，得到式E-5表示的白色固体，The compound of the formula E-5-1 is dissolved in toluene, then p-toluenesulfonic acid is added, and the mixture is stirred at room temperature. After the reaction is completed, the reaction solution is washed with a saturated aqueous solution of sodium hydrogencarbonate, and the organic layer is dried and concentrated. Purified to give a white solid of formula E-5.
    Figure PCTCN2018117201-appb-100012
    Figure PCTCN2018117201-appb-100012
    将式E-5的化合物溶解在甲醇中，然后加入氨甲醇溶液，室温搅拌后，加入三乙酰氧基硼氢化钠，继续搅拌，反应完毕，浓缩，将残余物分散于二氯甲烷与水中，水层再以二氯甲烷提取一次，合并有机层，无水硫酸钠干燥，过滤，浓缩，柱层析纯化，得白色固体，即为所述式E-11的葫芦素E的衍生物，The compound of the formula E-5 is dissolved in methanol, and then a solution of ammonia in methanol is added. After stirring at room temperature, sodium triacetoxyborohydride is added, stirring is continued, the reaction is completed, concentrated, and the residue is dispersed in dichloromethane and water. The aqueous layer is extracted once more with dichloromethane, and the organic layer is combined, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography to give a white solid, which is a derivative of cucurbitacin E of formula E-11,
    Figure PCTCN2018117201-appb-100013
    Figure PCTCN2018117201-appb-100013
    将式E-11的化合物溶解于甲醇中，然后加入氢氧化锂水溶液，室温搅拌，反应完毕，浓缩除去甲醇，残余物分散于二氯甲烷与水中，二氯甲烷层干燥，过滤，浓缩，得到白色固体，即为所述式E-15的葫芦素E的衍生物，The compound of the formula E-11 is dissolved in methanol, and then a lithium hydroxide aqueous solution is added thereto, and the mixture is stirred at room temperature. The reaction is completed, and the residue is evaporated to methylene chloride and water. The methylene chloride layer is dried, filtered and concentrated. a white solid, which is a derivative of the cucurbitacin E of the formula E-15,
    Figure PCTCN2018117201-appb-100014
    Figure PCTCN2018117201-appb-100014
    或者，将式E-11化合物溶解在乙醇中，然后加入钯碳，氮气置换，然后氢气置换，保持2atm压力，搅拌反应，过滤，浓缩，得白色固体，即为所述式E-12的葫芦素E的衍生物，Alternatively, the compound of the formula E-11 is dissolved in ethanol, then palladium carbon is added, the nitrogen is replaced, then the hydrogen is replaced, the pressure is maintained at 2 atm, the reaction is stirred, filtered, and concentrated to give a white solid, which is the cucurbit of the formula E-12. a derivative of E,
    Figure PCTCN2018117201-appb-100015
    Figure PCTCN2018117201-appb-100015
    将式E-12的化合物溶解于甲醇中，然后加入氢氧化锂水溶液，室温搅拌，反应完毕，浓缩除去甲醇，残余物分散于二氯甲烷与水中，二氯甲烷层干燥，过滤，浓缩，得到白色固体，即为所述式E-16的葫芦素E的衍生物，The compound of the formula E-12 is dissolved in methanol, and then an aqueous lithium hydroxide solution is added thereto, and the mixture is stirred at room temperature. The reaction is completed, and the mixture is evaporated to remove methanol. The residue is dissolved in dichloromethane and water. a white solid, which is a derivative of the cucurbitacin E of the formula E-16,
    Figure PCTCN2018117201-appb-100016
    Figure PCTCN2018117201-appb-100016
  4. 制备式E-13或式E-14的葫芦素E衍生物的方法，其特征在于：A process for the preparation of a cucurbitacin E derivative of formula E-13 or formula E-14, characterized in that:
    将葫芦素E溶解在甲醇中，然后加入氢氧化锂水溶液，室温搅拌，浓缩，残余物以二氯甲烷溶解，以碱水洗涤，有机层干燥浓缩，得式E-1-1表示的白色固体，The cucurbitacin E is dissolved in methanol, and then an aqueous solution of lithium hydroxide is added thereto, stirred at room temperature, concentrated, and the residue is dissolved in dichloromethane, washed with aqueous alkali and dried and concentrated to give a white solid of formula E-1-1. ,
    Figure PCTCN2018117201-appb-100017
    Figure PCTCN2018117201-appb-100017
    将式E-1-1表示的化合物溶解在甲醇中，然后加入氨甲醇溶液，室温搅拌，加入三乙酰氧基硼氢化钠，继续搅拌，反应完毕，浓缩，将残余物分散于二氯甲烷与水中，水层再以二氯甲烷提取一次，合并有机层，无水硫酸钠干燥，过滤，浓缩，柱层析纯化，得到白色固体，即为所述式E-13的葫芦素E的衍生物，The compound represented by the formula E-1-1 is dissolved in methanol, then added with a solution of ammonia in methanol, stirred at room temperature, sodium triacetoxyborohydride is added, stirring is continued, the reaction is completed, concentrated, and the residue is dispersed in dichloromethane. In water, the aqueous layer is extracted once more with dichloromethane, and the organic layer is combined, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography to give a white solid, which is a derivative of cucurbitacin E of formula E-13 ,
    Figure PCTCN2018117201-appb-100018
    Figure PCTCN2018117201-appb-100018
    将式E-13的葫芦素E的衍生物溶解在乙醇中，然后加入钯碳，氮气置换，然后氢气置换，保持2atm压力，搅拌反应，过滤，浓缩，得白色固体，即为所述式E-14的葫芦素E的衍生物，The derivative of cucurbitacin E of formula E-13 is dissolved in ethanol, then added with palladium carbon, replaced with nitrogen, then replaced with hydrogen, maintained at a pressure of 2 atm, stirred, filtered, and concentrated to give a white solid. -14 derivatives of cucurbitacin E,
    Figure PCTCN2018117201-appb-100019
    Figure PCTCN2018117201-appb-100019
  5. 制备式E-17、式E-18、式E-19、式E-20、式E-23或式E-24的葫芦素E衍生物的方法，其特征在于：Process for the preparation of a cucurbitacin E derivative of formula E-17, formula E-18, formula E-19, formula E-20, formula E-23 or formula E-24, characterized in that:
    Figure PCTCN2018117201-appb-100020
    Figure PCTCN2018117201-appb-100020
    将式E-23-02的化合物溶解在甲醇中，然后加入氢氧化锂水溶液，室温搅拌，浓缩，残余物以二氯甲烷溶解，以碱水洗涤，有机层干燥浓缩，得白色固体，即为所述式E-23的葫芦素E的衍生物，The compound of the formula E-23-02 is dissolved in methanol, then aqueous lithium hydroxide solution is added, the mixture is stirred at room temperature, and the residue is evaporated. a derivative of cucurbitacin E of the formula E-23,
    Figure PCTCN2018117201-appb-100021
    Figure PCTCN2018117201-appb-100021
    将式E-23化合物溶解在乙醇中，然后加入钯碳，氮气置换，然后氢气置换， 保持2atm压力，搅拌反应，过滤，浓缩，得白色固体，即为所述式E-24的葫芦素E的衍生物，The compound of the formula E-23 is dissolved in ethanol, then palladium carbon is added, replaced with nitrogen, then replaced with hydrogen, maintained at a pressure of 2 atm, stirred, filtered, and concentrated to give a white solid, which is the cucurbitacin E of the formula E-24. Derivatives,
    Figure PCTCN2018117201-appb-100022
    Figure PCTCN2018117201-appb-100022
    或者，将式E-23化合物溶解在二氯甲烷中，然后加入吡啶，再加入丙酰氯，室温反应，反应完毕，反应液以酸水洗涤，有机层干燥浓缩，残余物柱层析纯化得到白色固体，即为所述式E-17的葫芦素E的衍生物，Alternatively, the compound of the formula E-23 is dissolved in dichloromethane, then pyridine is added, then propionyl chloride is added, and the reaction is carried out at room temperature. The reaction is completed, the reaction solution is washed with acid water, the organic layer is dried and concentrated, and the residue is purified by column chromatography to yield white. a solid, which is a derivative of the cucurbitacin E of the formula E-17,
    Figure PCTCN2018117201-appb-100023
    Figure PCTCN2018117201-appb-100023
    将式E-17化合物溶解在乙醇中，然后加入钯碳，氮气置换，然后氢气置换，保持2atm压力，搅拌反应，过滤，浓缩，得白色固体，即为所述式E-19的葫芦素E的衍生物，Dissolving the compound of formula E-17 in ethanol, then adding palladium carbon, replacing with nitrogen, then replacing with hydrogen, maintaining a pressure of 2 atm, stirring the reaction, filtering, and concentrating to obtain a white solid, which is the cucurbitacin E of the formula E-19. Derivatives,
    Figure PCTCN2018117201-appb-100024
    Figure PCTCN2018117201-appb-100024
    或者，将式E-23化合物溶解在二氯甲烷中，然后加入吡啶，再加入丁酰氯，室温反应，反应完毕，反应液以酸水洗涤，有机层干燥浓缩，残余物柱层析纯化得到白色固体，即为所述式E-18的葫芦素E的衍生物，Alternatively, the compound of the formula E-23 is dissolved in dichloromethane, then pyridine is added, then butyryl chloride is added, and the reaction is carried out at room temperature. The reaction is completed, the reaction solution is washed with acid water, the organic layer is dried and concentrated, and the residue is purified by column chromatography. a solid, which is a derivative of the cucurbitacin E of the formula E-18,
    Figure PCTCN2018117201-appb-100025
    Figure PCTCN2018117201-appb-100025
    将式E-18化合物溶解在乙醇中，然后加入钯碳，氮气置换，然后氢气置换，保持2atm压力，搅拌反应，过滤，浓缩，得白色固体，即为所述式E-20的葫芦素E的衍生物，Dissolving the compound of formula E-18 in ethanol, then adding palladium carbon, replacing with nitrogen, then replacing with hydrogen, maintaining a pressure of 2 atm, stirring the reaction, filtering, and concentrating to obtain a white solid, which is the cucurbitacin E of the formula E-20. Derivatives,
    Figure PCTCN2018117201-appb-100026
    Figure PCTCN2018117201-appb-100026
  6. 制备式E-21、式E-22、式E-25或式E-26的葫芦素E衍生物的方法，其特征在于：Process for the preparation of a cucurbitacin E derivative of formula E-21, formula E-22, formula E-25 or formula E-26, characterized in that:
    Figure PCTCN2018117201-appb-100027
    Figure PCTCN2018117201-appb-100027
    将式E-21-01化合物溶解在甲苯中，然后加入对甲苯磺酸，室温搅拌，反应完毕，往反应液中加入饱和碳酸氢钠水溶液洗涤，有机层干燥浓缩，残余物以柱层析纯化，得白色固体，即为所述式E-21的葫芦素E的衍生物，The compound of the formula E-21-01 is dissolved in toluene, then p-toluenesulfonic acid is added, and the mixture is stirred at room temperature. After the reaction is completed, the reaction solution is washed with a saturated aqueous solution of sodium hydrogencarbonate, the organic layer is dried and concentrated, and the residue is purified by column chromatography. , a white solid, which is a derivative of the cucurbitacin E of the formula E-21,
    Figure PCTCN2018117201-appb-100028
    Figure PCTCN2018117201-appb-100028
    将式E-21化合物溶解在甲醇中，然后加入氢氧化锂水溶液，室温搅拌，浓 缩，残余物以二氯甲烷溶解，以碱水洗涤，有机层干燥浓缩，得白色固体，即为所述式E-25的葫芦素E的衍生物，The compound of the formula E-21 is dissolved in methanol, then aqueous lithium hydroxide solution is added, stirred at room temperature, concentrated, and the residue is dissolved in dichloromethane, washed with EtOAc EtOAc a derivative of cucurbitacin E of E-25,
    Figure PCTCN2018117201-appb-100029
    Figure PCTCN2018117201-appb-100029
    或者，将式E-21化合物溶解在乙醇中，然后加入钯碳，氮气置换，然后氢气置换，保持2atm压力，搅拌反应，过滤，浓缩，得白色固体，即为所述式E-22的葫芦素E的衍生物，Alternatively, the compound of the formula E-21 is dissolved in ethanol, then palladium carbon is added, the nitrogen is replaced, then the hydrogen is replaced, the pressure is maintained at 2 atm, the reaction is stirred, filtered, and concentrated to give a white solid, which is the cucurbit of the formula E-22. a derivative of E,
    Figure PCTCN2018117201-appb-100030
    Figure PCTCN2018117201-appb-100030
    将式E-22化合物溶解在甲醇中，然后加入氢氧化锂水溶液，室温搅拌，浓缩，残余物以二氯甲烷溶解，以碱水洗涤，有机层干燥浓缩，得白色固体，即为所述式E-26的葫芦素E的衍生物，The compound of the formula E-22 is dissolved in methanol, then aqueous lithium hydroxide solution is added, stirred at room temperature, concentrated, and the residue is dissolved in dichloromethane, washed with EtOAc. a derivative of cucurbitacin E of E-26,
    Figure PCTCN2018117201-appb-100031
    Figure PCTCN2018117201-appb-100031
  7. 下式表示葫芦素B衍生物，或者其药学上可接受的盐：The following formula represents a cucurbitacin B derivative, or a pharmaceutically acceptable salt thereof:
    Figure PCTCN2018117201-appb-100032
    Figure PCTCN2018117201-appb-100032
    Figure PCTCN2018117201-appb-100033
    Figure PCTCN2018117201-appb-100033
    Figure PCTCN2018117201-appb-100034
    Figure PCTCN2018117201-appb-100034
  8. 制备式B-7、式B-8、式B-9或式B-10的葫芦素B衍生物的方法，其特征在于：A process for the preparation of a cucurbitacin B derivative of the formula B-7, formula B-8, formula B-9 or formula B-10, characterized in that:
    将葫芦素B溶解在甲醇中，然后加入氢氧化锂水溶液，室温搅拌，浓缩，残余物以二氯甲烷溶解，以碱水洗涤，有机层干燥浓缩，得式B-1-1表示的白色固体，The cucurbitacin B is dissolved in methanol, and then an aqueous lithium hydroxide solution is added thereto, stirred at room temperature, concentrated, and the residue is dissolved in dichloromethane, washed with aqueous alkali and dried and concentrated to give a white solid of formula B-1-1. ,
    Figure PCTCN2018117201-appb-100035
    Figure PCTCN2018117201-appb-100035
    将式B-1-1表示的化合物溶解在二氯甲烷中，然后加入吡啶，再加入丙酰氯，室温反应，反应完毕，反应液以酸水洗涤，有机层干燥浓缩，残余物柱层析纯化得到式B-1表示的白色固体，The compound represented by the formula B-1-1 is dissolved in dichloromethane, then pyridine is added, and propionyl chloride is added thereto, and the reaction is carried out at room temperature. The reaction is completed, the reaction solution is washed with acid water, the organic layer is dried and concentrated, and the residue is purified by column chromatography. A white solid represented by the formula B-1 is obtained,
    Figure PCTCN2018117201-appb-100036
    Figure PCTCN2018117201-appb-100036
    将式B-1表示的化合物溶解在甲醇中，然后加入氨甲醇溶液，室温搅拌，加入三乙酰氧基硼氢化钠，继续搅拌，反应完毕，浓缩，将残余物分散于二氯甲烷与水中，水层再以二氯甲烷提取一次，合并有机层，无水硫酸钠干燥，过滤，浓缩，柱层析纯化得到白色固体，即为所述式B-7的葫芦素B的衍生物，The compound represented by the formula B-1 is dissolved in methanol, then added with a methanol solution of ammonia, stirred at room temperature, sodium triacetoxyborohydride is added, stirring is continued, the reaction is completed, concentrated, and the residue is dispersed in dichloromethane and water. The aqueous layer is extracted once more with dichloromethane, and the organic layer is combined, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography to give a white solid, which is a derivative of cucurbitacin B of formula B-7,
    Figure PCTCN2018117201-appb-100037
    Figure PCTCN2018117201-appb-100037
    将式B-7的葫芦素B的衍生物溶解在乙醇中，然后加入钯碳，氮气置换，然后氢气置换，保持2atm压力，搅拌反应，过滤，浓缩，得白色固体，即为所述式B-9的葫芦素B的衍生物，Dissolving the derivative of cucurbitacin B of formula B-7 in ethanol, then adding palladium carbon, replacing with nitrogen, then replacing with hydrogen, maintaining a pressure of 2 atm, stirring the reaction, filtering, and concentrating to obtain a white solid, that is, the formula B a derivative of cucurbitacin B, -9
    Figure PCTCN2018117201-appb-100038
    Figure PCTCN2018117201-appb-100038
    或者，式B-1-1的化合物溶解在二氯甲烷中，然后加入吡啶，再加入丁酰氯，室温反应，反应完毕，反应液以酸水洗涤，有机层干燥浓缩，残余物柱层析纯化得到式B-2表示的白色固体，Alternatively, the compound of the formula B-1-1 is dissolved in dichloromethane, then pyridine is added, then butyryl chloride is added, and the reaction is carried out at room temperature. The reaction is completed, the reaction solution is washed with acid water, the organic layer is dried and concentrated, and the residue is purified by column chromatography. A white solid represented by the formula B-2 is obtained,
    Figure PCTCN2018117201-appb-100039
    Figure PCTCN2018117201-appb-100039
    将式B-2表示的化合物溶解在甲醇中，然后加入氨甲醇溶液，室温搅拌后，加入三乙酰氧基硼氢化钠，继续搅拌，反应完毕，浓缩，将残余物分散于二氯甲烷与水中，水层再以二氯甲烷提取一次，合并有机层，无水硫酸钠干燥，过滤，浓缩，柱层析纯化得到白色固体，即为所述式B-8的葫芦素B的衍生物，The compound represented by the formula B-2 is dissolved in methanol, and then an ammonia methanol solution is added. After stirring at room temperature, sodium triacetoxyborohydride is added, stirring is continued, the reaction is completed, and the residue is dispersed in dichloromethane and water. The aqueous layer is extracted once more with dichloromethane, and the organic layer is combined, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography to obtain a white solid, which is a derivative of cucurbitacin B of the formula B-8,
    Figure PCTCN2018117201-appb-100040
    Figure PCTCN2018117201-appb-100040
    将式B-8的葫芦素B的衍生物溶解在乙醇中，然后加入钯碳，氮气置换，然后氢气置换，保持2atm压力，搅拌反应，过滤，浓缩，得白色固体，即为所述式B-10的葫芦素B的衍生物，Dissolving the derivative of cucurbitacin B of formula B-8 in ethanol, then adding palladium carbon, replacing with nitrogen, then replacing with hydrogen, maintaining a pressure of 2 atm, stirring the reaction, filtering, and concentrating to obtain a white solid, that is, the formula B -10 derivatives of cucurbitacin B,
    Figure PCTCN2018117201-appb-100041
    Figure PCTCN2018117201-appb-100041
  9. 制备式B-11、式B-12、式B-15或式B-16的葫芦素B衍生物的方法，其特征在于，A method for producing a cucurbitacin B derivative of the formula B-11, formula B-12, formula B-15 or formula B-16, characterized in that
    将葡萄糖溶解在丙酮中，然后加入1，1-二甲氧基丙烷以及硫酸，室温搅拌，浓缩至尽，残余物用乙酸乙酯溶解，以水洗涤，有机层干燥浓缩，得到式G-1表示的无色油状物，The glucose is dissolved in acetone, then 1,1-dimethoxypropane and sulfuric acid are added, and the mixture is stirred at room temperature, and the residue is concentrated to dryness. a colorless oil,
    Figure PCTCN2018117201-appb-100042
    Figure PCTCN2018117201-appb-100042
    将葫芦素B、式G-1表示的化合物、氧化锌溶解在甲醇中，室温搅拌，浓缩至尽，残余物用乙酸乙酯溶解，以饱和盐水洗涤，有机层干燥浓缩，剩余物以柱层析纯化，得到式B-5-1表示的白色固体，The cucurbitacin B, the compound represented by the formula G-1, and the zinc oxide are dissolved in methanol, stirred at room temperature, and concentrated to the end. The residue is dissolved in ethyl acetate, washed with saturated brine, and then dried and concentrated. Purification to obtain a white solid represented by formula B-5-1.
    Figure PCTCN2018117201-appb-100043
    Figure PCTCN2018117201-appb-100043
    将式B-5-1的化合物溶解在甲苯中，然后加入对甲苯磺酸，室温搅拌，反应完毕，往反应液中加入饱和碳酸氢钠水溶液洗涤，有机层干燥浓缩，残余物以柱层析纯化，得到式B-5表示的白色固体，The compound of the formula B-5-1 is dissolved in toluene, then p-toluenesulfonic acid is added, and the mixture is stirred at room temperature. After the reaction is completed, the reaction solution is washed with a saturated aqueous solution of sodium hydrogencarbonate, and the organic layer is dried and concentrated. Purified to give a white solid of formula B-5.
    Figure PCTCN2018117201-appb-100044
    Figure PCTCN2018117201-appb-100044
    将式B-5的化合物溶解在甲醇中，然后加入氨甲醇溶液，室温搅拌后，加入三乙酰氧基硼氢化钠，继续搅拌，反应完毕，浓缩，将残余物分散于二氯甲烷与水中，水层再以二氯甲烷提取一次，合并有机层，无水硫酸钠干燥，过滤，浓缩，柱层析纯化，得白色固体，即为所述式B-11的葫芦素B的衍生物，The compound of the formula B-5 is dissolved in methanol, and then a solution of ammonia in methanol is added. After stirring at room temperature, sodium triacetoxyborohydride is added, stirring is continued, the reaction is completed, and the residue is dispersed in dichloromethane and water. The aqueous layer is extracted once more with dichloromethane, and the organic layer is combined, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography to give a white solid, which is a derivative of cucurbitacin B of formula B-11,
    Figure PCTCN2018117201-appb-100045
    Figure PCTCN2018117201-appb-100045
    将式B-11的化合物溶解于甲醇中，然后加入氢氧化锂水溶液，室温搅拌，反应完毕，浓缩除去甲醇，残余物分散于二氯甲烷与水中，二氯甲烷层干燥，过滤，浓缩，得到白色固体，即为所述式B-15的葫芦素B的衍生物，The compound of the formula B-11 is dissolved in methanol, and then an aqueous lithium hydroxide solution is added thereto, and the mixture is stirred at room temperature. The reaction is completed, and the residue is evaporated to dichloromethane. a white solid, which is a derivative of the cucurbitacin B of the formula B-15,
    Figure PCTCN2018117201-appb-100046
    Figure PCTCN2018117201-appb-100046
    或者，将式B-11化合物溶解在乙醇中，然后加入钯碳，氮气置换，然后氢气置换，保持2atm压力，搅拌反应，过滤，浓缩，得白色固体，即为所述式B-12的葫芦素B的衍生物，Alternatively, the compound of the formula B-11 is dissolved in ethanol, then palladium carbon is added, replaced with nitrogen, then replaced with hydrogen, maintained at a pressure of 2 atm, stirred, filtered, and concentrated to give a white solid, which is the cucurbit of the formula B-12. a derivative of B,
    Figure PCTCN2018117201-appb-100047
    Figure PCTCN2018117201-appb-100047
    将式B-12的化合物溶解于甲醇中，然后加入氢氧化锂水溶液，室温搅拌，反应完毕，浓缩除去甲醇，残余物分散于二氯甲烷与水中，二氯甲烷层干燥，过滤，浓缩，得到白色固体，即为所述式B-16的葫芦素B的衍生物，The compound of the formula B-12 is dissolved in methanol, and then an aqueous lithium hydroxide solution is added thereto, and the mixture is stirred at room temperature. The reaction is completed, and the residue is evaporated to methylene chloride and water. The methylene chloride layer is dried, filtered and concentrated. a white solid, which is a derivative of the cucurbitacin B of the formula B-16,
    Figure PCTCN2018117201-appb-100048
    Figure PCTCN2018117201-appb-100048
  10. 制备式B-13或式B-14的葫芦素B衍生物的方法，其特征在于，A method for producing a cucurbitacin B derivative of the formula B-13 or the formula B-14, characterized in that
    将葫芦素B溶解在甲醇中，然后加入氢氧化锂水溶液，室温搅拌，浓缩，残余物以二氯甲烷溶解，以碱水洗涤，有机层干燥浓缩，得式B-1-1表示的白色固体，The cucurbitacin B is dissolved in methanol, and then an aqueous lithium hydroxide solution is added thereto, stirred at room temperature, concentrated, and the residue is dissolved in dichloromethane, washed with aqueous alkali and dried and concentrated to give a white solid of formula B-1-1. ,
    Figure PCTCN2018117201-appb-100049
    Figure PCTCN2018117201-appb-100049
    将式B-1-1表示的化合物溶解在甲醇中，然后加入氨甲醇溶液，室温搅拌，加入三乙酰氧基硼氢化钠，继续搅拌，反应完毕，浓缩，将残余物分散于二氯甲烷与水中，水层再以二氯甲烷提取一次，合并有机层，无水硫酸钠干燥，过滤，浓缩，柱层析纯化，得到白色固体，即为所述式B-13的葫芦素B的衍生物，The compound represented by the formula B-1-1 is dissolved in methanol, then added with an ammonia methanol solution, stirred at room temperature, sodium triacetoxyborohydride is added, stirring is continued, the reaction is completed, concentrated, and the residue is dispersed in dichloromethane. In water, the aqueous layer is extracted once more with dichloromethane, and the organic layer is combined, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography to give white solid, which is the derivative of cucurbitacin B of formula B-13 ,
    Figure PCTCN2018117201-appb-100050
    Figure PCTCN2018117201-appb-100050
    将式B-13的葫芦素E的衍生物溶解在乙醇中，然后加入钯碳，氮气置换，然后氢气置换，保持2atm压力，搅拌反应，过滤，浓缩，得白色固体，即为所述式B-14的葫芦素B的衍生物，Dissolving the derivative of cucurbitacin E of formula B-13 in ethanol, then adding palladium carbon, replacing with nitrogen, then replacing with hydrogen, maintaining a pressure of 2 atm, stirring the reaction, filtering, and concentrating to obtain a white solid, that is, the formula B -14 derivative of cucurbitacin B,
    Figure PCTCN2018117201-appb-100051
    Figure PCTCN2018117201-appb-100051
  11. 制备式B-17、式B-18、式B-19、式B-20、式B-21、式B-23、式B-23、式B-24、式B-25或式B-26的葫芦素B衍生物的方法，其特征在于，Preparation of Formula B-17, Formula B-18, Formula B-19, Formula B-20, Formula B-21, Formula B-23, Formula B-23, Formula B-24, Formula B-25 or Formula B-26 Method for cucurbitacin B derivative, characterized in that
    Figure PCTCN2018117201-appb-100052
    Figure PCTCN2018117201-appb-100052
    将式E-17化合物溶解在甲醇中，然后加入氰基硼氢化钠，室温搅拌，反应完毕后，浓缩，残余物分散于水和二氯甲烷中，二氯甲烷层干燥，过滤，浓缩，柱层析，得到白色固体，即为所述式B-17的葫芦素E的衍生物，The compound of the formula E-17 is dissolved in methanol, then sodium cyanoborohydride is added, and the mixture is stirred at room temperature. After completion of the reaction, the mixture is concentrated, the residue is crystallised in water and methylene chloride. Chromatography to obtain a white solid, which is a derivative of the cucurbitacin E of the formula B-17,
    Figure PCTCN2018117201-appb-100053
    Figure PCTCN2018117201-appb-100053
    Figure PCTCN2018117201-appb-100054
    Figure PCTCN2018117201-appb-100054
    将式E-18化合物溶解在甲醇中，然后加入氰基硼氢化钠，室温搅拌，反应完毕后，浓缩，残余物分散于水和二氯甲烷中，二氯甲烷层干燥，过滤，浓缩，柱层析，得到白色固体，即为所述式B-18的葫芦素E的衍生物，The compound of the formula E-18 is dissolved in methanol, then sodium cyanoborohydride is added, and the mixture is stirred at room temperature. After completion of the reaction, the mixture is concentrated, the residue is crystallised in water and methylene chloride. Chromatography to obtain a white solid, which is a derivative of the cucurbitacin E of the formula B-18,
    Figure PCTCN2018117201-appb-100055
    Figure PCTCN2018117201-appb-100055
    将式E-19化合物溶解在甲醇中，然后加入氰基硼氢化钠，室温搅拌，反应完毕后，浓缩，残余物分散于水和二氯甲烷中，二氯甲烷层干燥，过滤，浓缩，柱层析，得到白色固体，即为所述式B-19的葫芦素E的衍生物，The compound of the formula E-19 is dissolved in methanol, then sodium cyanoborohydride is added, and the mixture is stirred at room temperature. After completion of the reaction, the mixture is concentrated, the residue is crystallised in water and methylene chloride. Chromatography to obtain a white solid, which is a derivative of the cucurbitacin E of the formula B-19,
    Figure PCTCN2018117201-appb-100056
    Figure PCTCN2018117201-appb-100056
    Figure PCTCN2018117201-appb-100057
    Figure PCTCN2018117201-appb-100057
    将式E-20化合物溶解在甲醇中，然后加入氰基硼氢化钠，室温搅拌，反应完毕后，浓缩，残余物分散于水和二氯甲烷中，二氯甲烷层干燥，过滤，浓缩，柱层析，得到白色固体，即为所述式B-20的葫芦素E的衍生物，The compound of the formula E-20 is dissolved in methanol, then sodium cyanoborohydride is added, and the mixture is stirred at room temperature. After completion of the reaction, the mixture is concentrated, the residue is crystallised in water and methylene chloride. Chromatography to obtain a white solid, which is a derivative of the cucurbitacin E of the formula B-20,
    Figure PCTCN2018117201-appb-100058
    Figure PCTCN2018117201-appb-100058
    将式E-21化合物溶解在甲醇中，然后加入氰基硼氢化钠，室温搅拌，反应完毕后，浓缩，残余物分散于水和二氯甲烷中，二氯甲烷层干燥，过滤，浓缩，柱层析，得到白色固体，即为所述式B-21的葫芦素E的衍生物，The compound of the formula E-21 is dissolved in methanol, then sodium cyanoborohydride is added, and the mixture is stirred at room temperature. After completion of the reaction, the mixture is concentrated, and the residue is crystallised in water and dichloromethane. Chromatography to obtain a white solid, which is a derivative of the cucurbitacin E of the formula B-21,
    Figure PCTCN2018117201-appb-100059
    Figure PCTCN2018117201-appb-100059
    Figure PCTCN2018117201-appb-100060
    Figure PCTCN2018117201-appb-100060
    将式E-22化合物溶解在甲醇中，然后加入氰基硼氢化钠，室温搅拌，反应完毕后，浓缩，残余物分散于水和二氯甲烷中，二氯甲烷层干燥，过滤，浓缩，柱层析，得到白色固体，即为所述式B-22的葫芦素E的衍生物，The compound of the formula E-22 is dissolved in methanol, then sodium cyanoborohydride is added, and the mixture is stirred at room temperature. After completion of the reaction, the mixture is concentrated, the residue is crystallised in water and methylene chloride. Chromatography to obtain a white solid, which is a derivative of the cucurbitacin E of the formula B-22,
    Figure PCTCN2018117201-appb-100061
    Figure PCTCN2018117201-appb-100061
    将式E-23化合物溶解在甲醇中，然后加入氰基硼氢化钠，室温搅拌，反应完毕后，浓缩，残余物分散于水和二氯甲烷中，二氯甲烷层干燥，过滤，浓缩，柱层析，得到白色固体，即为所述式B-23的葫芦素E的衍生物，The compound of the formula E-23 is dissolved in methanol, then sodium cyanoborohydride is added, and the mixture is stirred at room temperature. After completion of the reaction, the mixture is concentrated. The residue is crystallised from water and methylene chloride. Chromatography to obtain a white solid, which is a derivative of the cucurbitacin E of the formula B-23,
    Figure PCTCN2018117201-appb-100062
    Figure PCTCN2018117201-appb-100062
    Figure PCTCN2018117201-appb-100063
    Figure PCTCN2018117201-appb-100063
    将式E-24化合物溶解在甲醇中，然后加入氰基硼氢化钠，室温搅拌，反应完毕后，浓缩，残余物分散于水和二氯甲烷中，二氯甲烷层干燥，过滤，浓缩，柱层析，得到白色固体，即为所述式B-24的葫芦素E的衍生物，The compound of the formula E-24 is dissolved in methanol, then sodium cyanoborohydride is added, and the mixture is stirred at room temperature. After completion of the reaction, the mixture is concentrated, the residue is crystallised in water and methylene chloride. Chromatography to obtain a white solid, which is a derivative of the cucurbitacin E of the formula B-24,
    Figure PCTCN2018117201-appb-100064
    Figure PCTCN2018117201-appb-100064
    将式E-25化合物溶解在甲醇中，然后加入氰基硼氢化钠，室温搅拌，反应完毕后，浓缩，残余物分散于水和二氯甲烷中，二氯甲烷层干燥，过滤，浓缩，柱层析，得到白色固体，即为所述式B-25的葫芦素E的衍生物，The compound of the formula E-25 is dissolved in methanol, then sodium cyanoborohydride is added, and the mixture is stirred at room temperature. After completion of the reaction, the mixture is concentrated, the residue is crystallised in water and methylene chloride. Chromatography to obtain a white solid, which is a derivative of the cucurbitacin E of the formula B-25,
    Figure PCTCN2018117201-appb-100065
    Figure PCTCN2018117201-appb-100065
    Figure PCTCN2018117201-appb-100066
    Figure PCTCN2018117201-appb-100066
    将式E-26化合物溶解在甲醇中，然后加入氰基硼氢化钠，室温搅拌，反应完毕后，浓缩，残余物分散于水和二氯甲烷中，二氯甲烷层干燥，过滤，浓缩，柱层析，得到白色固体，即为所述式B-26的葫芦素E的衍生物，The compound of the formula E-26 is dissolved in methanol, then sodium cyanoborohydride is added, and the mixture is stirred at room temperature. After completion of the reaction, the mixture is concentrated. The residue is crystallised from water and methylene chloride. Chromatography to obtain a white solid, which is a derivative of the cucurbitacin E of the formula B-26,
    Figure PCTCN2018117201-appb-100067
    Figure PCTCN2018117201-appb-100067
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