benzyl 3β-[(3-carboxy)propionyloxy]olean-12-en-28-oate | 1043913-97-8

• 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: benzyl 3β-[(3-carboxy)propionyloxy]olean-12-en-28-oate
• 英文别名: 3β-((3-carboxypropanoyl)oxy)olean-12-en-28-oic acid benzyl ester；4-[[(3S,4aR,6aR,6bS,8aS,12aS,14aR,14bR)-8a-benzyloxycarbonyl-4,4,6a,6b,11,11,14b-heptamethyl-1,2,3,4a,5,6,7,8,9,10,12,12a,14,14a-tetradecahydropicen-3-yl]oxy]-4-oxo-butanoic acid；4-[[(3S,4aR,6aR,6bS,8aS,12aS,14aR,14bR)-4,4,6a,6b,11,11,14b-heptamethyl-8a-phenylmethoxycarbonyl-1,2,3,4a,5,6,7,8,9,10,12,12a,14,14a-tetradecahydropicen-3-yl]oxy]-4-oxobutanoic acid
• CAS: 1043913-97-8
• 化学式: C₄₁H₅₈O₆
• 分子量: 646.908
• InChiKey: UWXFJMKVPQLTQY-QIDXFHPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.3
• 重原子数：
  47
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  89.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  benzyl 3β-[(3-carboxy)propionyloxy]olean-12-en-28-oate 在 三乙胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 25.0h， 生成 benzyl 3β-{4-oxo-4-[(2-sulfoethyl)amino]butyryloxy}olean-12-en-28-oate
  参考文献：
  名称：

  Synthesis and cytotoxicity evaluation of oleanolic acid derivatives

  摘要：

  Twelve derivatives of oleanolic acid (1) have been synthesized and evaluated for their inhibitory activities against the growth of prostate PC3, breast MCF-7, lung A549, and gastric BGC-823 cancer cells by MU assays. Within these series of derivatives, compound 17 exhibited the most potent cytotoxicity against PC3 cell line (IC50 = 0.39 mu M) and compound 28 displayed the best activity against A549 cell line (IC50 = 0.22 mu M). SAR analysis indicates that H-donor substitution at C-3 position of oleanolic acid may be advantageous for improvement of cytotoxicity against PC3, A549 and MCF-7 cell lines. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.01.129
• 作为产物：
  描述：

  齐墩果酸 在 吡啶 、 4-二甲氨基吡啶 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 benzyl 3β-[(3-carboxy)propionyloxy]olean-12-en-28-oate
  参考文献：
  名称：

  基于片段的新型五环三萜衍生物作为胆固醇酯转移蛋白抑制剂的发现

  摘要：

  胆固醇酯转移蛋白（CETP）是治疗动脉粥样硬化性心血管疾病的重要治疗靶标。我们的分子建模研究表明，五环三萜化合物可通过占据内源性配体胆固醇酯（CE）的结合位点来模拟其蛋白质-配体相互作用。齐墩果酸（OA），熊果酸（UA）的对接构象和已知CETP抑制剂Torcetrapib在活性位点的晶体构象的比对提出了基于片段的药物设计（FBDD）方法在本研究中的适用性。因此，已经设计并合成了一系列五环三萜类衍生物作为新型CETP抑制剂。最有效的化合物12e（IC 50：0.28μM）验证了我们的分子设计策略。分子动力学模拟表明，与OA衍生物12b相比，UA衍生物12e与Ser191的氢键相互作用更稳定，与Val198，Phe463的疏水相互作用更强，这主要导致了它们对CETP的抑制活性显着不同。这些基于乌桑烷型支架的新型有效CETP抑制剂值得进一步研究。

  DOI：

  10.1016/j.ejmech.2016.09.098

文献信息

• Discovery of pentacyclic triterpene 3β-ester derivatives as a new class of cholesterol ester transfer protein inhibitors
  作者：Dongyin Chen、Xin Huang、Hongwen Zhou、Hanqiong Luo、Pengfei Wang、Yongzhi Chang、Xinyi He、Suiying Ni、Qingqing Shen、Guoshen Cao、Hongbin Sun、Xiaoan Wen、Jun Liu

  DOI：10.1016/j.ejmech.2017.08.012

  日期：2017.10

  A series of pentacyclic triterpene 3β-ester derivatives were designed, synthesized and evaluated as a new class of cholesteryl ester transfer protein (CETP) inhibitors for the treatment of dyslipidemia. In vitro screening assay showed that 5 out of 30 compounds displayed moderate inhibiting human CETP activity with IC50s less than 10 μM. Among them, compound 20 (IC50 = 2.3 μM) had the most potent biological

  设计，合成和评估了一系列五环三萜3β-酯衍生物，将其作为治疗血脂异常的一类新的胆固醇酯转移蛋白（CETP）抑制剂。体外筛选试验表明，30种化合物中有5种显示出适度的抑制人CETP活性，IC 50小于10μM。其中，化合物20（IC 50  = 2.3μM）具有最强的生物学活性，可有效改善人脂肪组织特异性CETP转基因（ap2-CETPTg）小鼠和豚鼠的血浆脂质水平。额外的安全性评估（豚鼠没有血压升高）和药代动力学研究表明，化合物20的潜在可药性 这是开发用于治疗血脂异常的新型CETP抑制剂的有希望的先导。
• Design, Synthesis, and Antihepatocellular Carcinoma Activity of Nitric Oxide Releasing Derivatives of Oleanolic Acid
  作者：Li Chen、Yihua Zhang、Xiangwen Kong、Edward Lan、Zhangjian Huang、Sixun Peng、Daniel L. Kaufman、Jide Tian

  DOI：10.1021/jm800167u

  日期：2008.8.1

  Novel furoxan-based nitric oxide (NO) releasing derivatives of oleanolic acid (OA) were synthesized for potential therapy of liver cancers. Six compounds produced high levels of NO in human hepatocellular carcinoma (HCC) cells and exhibited strong cytotoxicity selectively against HCC in vitro. Treatment with 8b or 16b significantly inhibited the growth of HCC tumors in vivo. These data provide a proof-in-principle

  合成了新型呋喃基一氧化氮 (NO) 释放齐墩果酸 (OA) 衍生物，用于肝癌的潜在治疗。六种化合物在人肝细胞癌 (HCC) 细胞中产生高水平的 NO，并在体外对 HCC 表现出强烈的细胞毒性。用 8b 或 16b 处理显着抑制了体内 HCC 肿瘤的生长。这些数据提供了原则上的证明，呋喃/OA 杂化物可用于人类肝癌的治疗干预。
• The oleanolic acid derivative, 3-O-succinyl-28-O-benzyl oleanolate, induces apoptosis in B16–F10 melanoma cells via the mitochondrial apoptotic pathway
  作者：Fernando J. Reyes-Zurita、Marta Medina-O'Donnell、Rosa M. Ferrer-Martin、Eva E. Rufino-Palomares、Samuel Martin-Fonseca、Francisco Rivas、Antonio Martínez、Andrés García-Granados、Amalia Pérez-Jiménez、Leticia García-Salguero、Juan Peragón、Khalida Mokhtari、Pedro P. Medina、Andrés Parra、José A. Lupiáñez

  DOI：10.1039/c6ra18879f

  日期：——

  Antiproliferative and proapoptotic effects of 3-O-succinyl-28-O-benzyl oleanolate on B16–F10 skin-melanoma cells.

  3-O-琥珀酰基-28-O-苄基齐墩果酸对B16-F10皮肤黑色素瘤细胞的抗增殖和促凋亡作用。
• Semi-synthesis of acylated triterpenes from olive-oil industry wastes for the development of anticancer and anti-HIV agents
  作者：Andres Parra、Samuel Martin-Fonseca、Francisco Rivas、Fernando J. Reyes-Zurita、Marta Medina-O'Donnell、Antonio Martinez、Andres Garcia-Granados、Jose A. Lupiañez、Fernando Albericio

  DOI：10.1016/j.ejmech.2013.12.049

  日期：2014.3

  A broad set of potential bioactive conjugate compounds has been semi-synthesized through solution and solid-phase organic procedures, coupling two natural pentacyclic triterpene acids, oleanolic (OA) and maslinic acids (MA), at the hydroxyl groups of the A-ring of the triterpene skeleton, with 10 different acyl groups. These acyl OA and MA derivatives have been tested for their anti-proliferative (against the bl6f10 murine melanoma cancer cells) and antiviral (as inhibitors of the HIV-1-protease) effects. Several derivatives have shown high levels of early and total apoptosis (up to 90%). Most of the compounds that exhibited anti-proliferative effects also generated ROS, probably involving the activation of an intrinsic apoptotic route. The only four compounds that did not cause the release of ROS could be related to the participation of a probable extrinsic activation of the apoptosis mechanism. A great number of these acyl OA and MA derivatives have proved to be potent inhibitors of the HIV-1-protease, the most active inhibitors having IC50 values between 0.31 and 15.6 mu M, these values being between 4 and 186 times lower than their non-acylated precursors. The potent activities exhibited in the apoptosis-activation processes and in the inhibition of the HIV-1-protease by some OA and MA acylated derivatives imply that these compounds could be used as new, safe, and effective anticancer and/or antiviral drugs. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Synthesis and cytotoxicity evaluation of oleanolic acid derivatives
  作者：Jia Hao、Jun Liu、Xiaoan Wen、Hongbin Sun

  DOI：10.1016/j.bmcl.2013.01.129

  日期：2013.4

  Twelve derivatives of oleanolic acid (1) have been synthesized and evaluated for their inhibitory activities against the growth of prostate PC3, breast MCF-7, lung A549, and gastric BGC-823 cancer cells by MU assays. Within these series of derivatives, compound 17 exhibited the most potent cytotoxicity against PC3 cell line (IC50 = 0.39 mu M) and compound 28 displayed the best activity against A549 cell line (IC50 = 0.22 mu M). SAR analysis indicates that H-donor substitution at C-3 position of oleanolic acid may be advantageous for improvement of cytotoxicity against PC3, A549 and MCF-7 cell lines. (C) 2013 Elsevier Ltd. All rights reserved.