methyl 2α-hydroxy-3β,23-isopropylidenedioxyurs-12-ene-28-oate | 19533-98-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: methyl 2α-hydroxy-3β,23-isopropylidenedioxyurs-12-ene-28-oate
• 英文别名: Methyl 3,23-O-isopropylideneasiatate；methyl (1R,2R,4R,5R,10R,11R,14R,15S,18S,21R,22S,23S)-4-hydroxy-2,7,7,10,14,15,21,22-octamethyl-6,8-dioxahexacyclo[12.12.0.02,11.05,10.015,24.018,23]hexacos-24-ene-18-carboxylate
• CAS: 19533-98-3
• 化学式: C₃₄H₅₄O₅
• 分子量: 542.8
• InChiKey: VAIJHUIHWZDTEZ-TWXGOCSMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  39
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 2α-hydroxy-3β,23-isopropylidenedioxyurs-12-ene-28-oate 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 13.0h， 生成 methyl 2-α-O-[4-(1-piperazinyl)-4-oxobutyryl]-3β,23-isopropylidenedioxyurs-12-ene-28-oate
  参考文献：
  名称：

  设计，合成和生物功能评价新型五环三萜带有O- [4-（1-哌嗪基）-4-氧代-丁酰基部分作为抗增殖剂。

  摘要：

  合成了一系列带有O- [4-（1-哌嗪基）-4-氧代-丁酰基部分的五环三萜衍生物，并研究了它们潜在的抗增殖活性。五环三萜类化合物的衍生物是通过四步或六步合成程序合成的。使用Cell Counting Kit-8方法评估活性研究，并对A549细胞，MCF-7细胞和Hela细胞进行Western印迹分析。化合物3-O- [4-（1-哌嗪基）-4-氧代-丁酰基] olean-12-ene-28-oate（OA-4）和化合物2-O- [4-（1-哌嗪基）-发现4-氧代-丁酰基] -3，23-二羟基urs-12-烯-28-油酸酯（AA-5）是有前途的抗增殖剂。这些化合物显示出进一步优化作为抗肿瘤药物的潜力。

  DOI：

  10.1016/j.bmcl.2015.08.076
• 作为产物：
  描述：

  积雪草苷 在 potassium carbonate 、 对甲苯磺酸 、 sodium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 methyl 2α-hydroxy-3β,23-isopropylidenedioxyurs-12-ene-28-oate
  参考文献：
  名称：

  设计，合成和生物功能评价新型五环三萜带有O- [4-（1-哌嗪基）-4-氧代-丁酰基部分作为抗增殖剂。

  摘要：

  合成了一系列带有O- [4-（1-哌嗪基）-4-氧代-丁酰基部分的五环三萜衍生物，并研究了它们潜在的抗增殖活性。五环三萜类化合物的衍生物是通过四步或六步合成程序合成的。使用Cell Counting Kit-8方法评估活性研究，并对A549细胞，MCF-7细胞和Hela细胞进行Western印迹分析。化合物3-O- [4-（1-哌嗪基）-4-氧代-丁酰基] olean-12-ene-28-oate（OA-4）和化合物2-O- [4-（1-哌嗪基）-发现4-氧代-丁酰基] -3，23-二羟基urs-12-烯-28-油酸酯（AA-5）是有前途的抗增殖剂。这些化合物显示出进一步优化作为抗肿瘤药物的潜力。

  DOI：

  10.1016/j.bmcl.2015.08.076

文献信息

• Antiproliferative, Cell-Cycle Dysregulation Effects of Novel Asiatic Acid Derivatives on Human Non-small Cell Lung Cancer Cells
  作者：Liang Wang、Jie Xu、Chunhui Zhao、Longxuan Zhao、Bin Feng

  DOI：10.1248/cpb.c13-00328

  日期：——

  Asiatic acid (AA) is a pentacyclic triterpene in Centella asiatica known to inhibit proliferation and induce apoptosis in several tumor cell lines. In the current study, we synthesized five AA derivatives and examined their inhibitory activities on growth in non-small cell lung cancer cell lines, A549 and PC9/G. Four derivatives were found to have stronger cell growth inhibitory activity than AA. Among them, compound A-3 showed the most significant antiproliferative effects on tumor. Growth of A549 and PC9/G cells was inhibited by A-3 in a dose- and time-dependent manner. To determine the cellular gene expression changes in A549 and PC9/G cells treated with A-3, Affymetrix GeneChip® Human Genome U133 Plus 2.0 Array were used to screen transcriptome differences. Expression levels of 1121 genes in A549 and 1873 genes in PC9/G were significantly altered upon treatment with 10 µM A-3 after 48 h, with 357 overlapping genes. The signaling pathways molecules involved in the antiproliferative and cell cycle dysregulation effects of A-3 identified using microarray were further validated via Western blot analyses. The results collectively indicate that A-3 induces inhibition of cell proliferation via downregulation of the Ras/Raf/MEK/ERK pathway and cell cycle arrest at G1/S and G2/M.

  亚细亚酸（AA）是一种在穿心莲中发现的五环三萜，已知能抑制多种肿瘤细胞系的增殖并诱导其凋亡。在本研究中，我们合成了五种AA衍生物，并检测了它们对非小细胞肺癌细胞系A549和PC9/G生长的抑制活性。发现其中四种衍生物的细胞生长抑制活性强于AA，其中化合物A-3对肿瘤的抗增殖作用最为显著。A-3以剂量和时间依赖的方式抑制A549和PC9/G细胞的生长。为了确定A-3处理后A549和PC9/G细胞的基因表达变化，我们使用Affymetrix GeneChip®人类基因组U133 Plus 2.0阵列筛选了转录组差异。经过10 µM A-3处理48小时后，A549细胞中1121个基因和PC9/G细胞中1873个基因的表达水平显著改变，其中357个基因重叠。通过微阵列识别的与A-3抗增殖和细胞周期失调效应相关的信号通路分子，进一步通过西方印迹分析验证。结果综合表明，A-3通过下调Ras/Raf/MEK/ERK通路和使细胞周期阻滞在G1/S和G2/M阶段来抑制细胞增殖。
• Inhibition of Human Enterovirus 71 Replication by Pentacyclic Triterpenes and Their Novel Synthetic Derivatives
  作者：Chun-hui Zhao、Jie Xu、Ying-qiu Zhang、Long-xuan Zhao、Bin Feng

  DOI：10.1248/cpb.c14-00088

  日期：——

  A large number of bioactive pentacyclic triterpenoids have been shown to have multiple biological activities. This study was conducted to evaluate the inhibitory activities of 6 newly synthesized and novel pentacyclic triterpenoids against enterovirus 71 (EV71). The parent compound, ursolic acid (UA), showed the greatest inhibitory activity against EV71, while oleanolic acid (OA), asiatic acid (AA), and synthetic derivatives of 18-β-glycyrrhetinic acid (GA) and OA also exhibited inhibitory effects, although to lesser extents. The results suggest these compounds show potential for further optimization as antiviral candidates for treatment of EV71 infections.

  大量具有生物活性的五环三萜类化合物被证明具有多种生物活性。本研究评估了 6 种新合成的新型五环三萜类化合物对肠病毒 71（EV71）的抑制活性。母体化合物熊果酸（UA）对 EV71 的抑制活性最强，齐墩果酸（OA）、积雪草酸（AA）以及 18-β-甘草次酸（GA）和 OA 的合成衍生物也有抑制作用，但程度较弱。结果表明，这些化合物具有进一步优化的潜力，可作为治疗 EV71 感染的候选抗病毒药物。
• Asiatic acid derivatives its manufacturing method and dermatological
  申请人：Dong Kook Pharmaceutical Co., Ltd.

  公开号：US05834437A1

  公开（公告）日：1998-11-10

  The object of the present invention is to provide asiatic acid derivatives, its pharmaceutically acceptable salts or esters. Asiatic acid, its trisaccharide asiaticoside and mddecassic acid, extracted from Centella asiatica have been used for a long time in the management of skin scars and chronic ulcers. In this invention, asiatic acid derivatives synthesized from asiatic acid show excellent wound-healing properties.

  本发明的目的是提供亚洲酸衍生物，其药学上可接受的盐或酯。长期以来，从积雪草中提取的亚洲酸、其三糖苷亚洲苷和去甲齐墩酸已被用于治疗皮肤疤痕和慢性溃疡。在本发明中，从亚洲酸合成的亚洲酸衍生物表现出优异的伤口愈合性能。
• Design, synthesis, and biofunctional evaluation of novel pentacyclic triterpenes bearing O-[4-(1-piperazinyl)-4-oxo-butyryl moiety as antiproliferative agents
  作者：Chun-hui Zhao、Cui-li Zhang、Jin-jie Shi、Xi-yan Hou、Bin Feng、Long-xuan Zhao

  DOI：10.1016/j.bmcl.2015.08.076

  日期：2015.10

  A series of pentacyclic triterpenoids derivatives bearing O-[4-(1-piperazinyl)-4-oxo-butyryl moiety has been synthesized and investigated for their potential antiproliferative activities. Pentacyclic triterpenoids derivative compounds were synthesized by a four or six step synthetic procedure. The activity studies were evaluated using Cell Counting Kit-8 method, and Western blotting analysis on A549

  合成了一系列带有O- [4-（1-哌嗪基）-4-氧代-丁酰基部分的五环三萜衍生物，并研究了它们潜在的抗增殖活性。五环三萜类化合物的衍生物是通过四步或六步合成程序合成的。使用Cell Counting Kit-8方法评估活性研究，并对A549细胞，MCF-7细胞和Hela细胞进行Western印迹分析。化合物3-O- [4-（1-哌嗪基）-4-氧代-丁酰基] olean-12-ene-28-oate（OA-4）和化合物2-O- [4-（1-哌嗪基）-发现4-氧代-丁酰基] -3，23-二羟基urs-12-烯-28-油酸酯（AA-5）是有前途的抗增殖剂。这些化合物显示出进一步优化作为抗肿瘤药物的潜力。