(3β,12α) 3,12-dihydroxy-18β-olean-28-oic acid 28,13-lactone | 19897-43-9

• 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: (3β,12α) 3,12-dihydroxy-18β-olean-28-oic acid 28,13-lactone
• 英文别名: 3β,12α-dihydroxy-oleanane-28,13β-olide；3β,12α-dihydroxyolean-13β,28-olide；3β,12α-dihydroxyolean-28,13β-olide；3,12-dihydroxy-28,13-oleananolide；oleanderolide；3β,12α,13-trihydroxy-oleanan-28-oic acid-13-lactone；(1S,4S,5R,8R,10S,13R,14R,16S,17S,18R)-10,16-dihydroxy-4,5,9,9,13,20,20-heptamethyl-24-oxahexacyclo[15.5.2.01,18.04,17.05,14.08,13]tetracosan-23-one
• CAS: 19897-43-9；38611-70-0
• 化学式: C₃₀H₄₈O₄
• 分子量: 472.709
• InChiKey: CXELEGXSGVFEND-NVTHVPAHSA-N

物化性质

• 熔点：
  247-249 °C
• 沸点：
  592.3±50.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  34
• 可旋转键数：
  0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.97
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	(3β,12α) 3,12-diacetoxy-olean-28-oic acid 28,13-lactone	85031-73-8	C34H52O6	556.783
  齐墩果酸 3-乙酸酯	oleanolic acid 3-acetate	4339-72-4	C32H50O4	498.747

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	(3β,12α) 3-acetyl-12-hydroxy-18β-olean-28-oic acid 28,13-lactone	62498-83-3	C32H50O5	514.746
  ——	(3β,12α) 3,12-diacetoxy-olean-28-oic acid 28,13-lactone	85031-73-8	C34H52O6	556.783
  ——	2-[[(1S,4S,5R,8R,10S,13R,14R,16S,17S,18R)-16-hydroxy-4,5,9,9,13,20,20-heptamethyl-23-oxo-24-oxahexacyclo[15.5.2.01,18.04,17.05,14.08,13]tetracosan-10-yl]oxycarbonyl]benzoic acid	1255647-25-6	C38H52O7	620.827
  ——	olean-12-oxo-4-hydroxy-3-carboxy-28-oic acid γ-lactone	1255647-24-5	C30H46O6	502.692
  ——	3,12-dioxooleanano-28,13-lactone	38611-69-7	C30H44O4	468.677
  ——	2-[[(1S,4S,5R,8R,10S,13R,14R,16S,17S,18R)-16-(2-carboxybenzoyl)oxy-4,5,9,9,13,20,20-heptamethyl-23-oxo-24-oxahexacyclo[15.5.2.01,18.04,17.05,14.08,13]tetracosan-10-yl]oxycarbonyl]benzoic acid	1255647-26-7	C46H56O10	768.945
  ——	[(1S,4S,5R,8R,10S,13S,17S,18R)-4,5,9,9,13,20,20-heptamethyl-16,23-dioxo-24-oxahexacyclo[15.5.2.01,18.04,17.05,14.08,13]tetracos-14-en-10-yl] acetate	676248-15-0	C32H46O5	510.714
  ——	(4aS,6aS,6bR,10S,12aR)-methyl 10-acetoxy-2,2,6a,6b,9,9,12a-heptamethyl-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-4a-carboxylate	——	C33H52O4	512.773
  齐墩果酸 3-乙酸酯	oleanolic acid 3-acetate	4339-72-4	C32H50O4	498.747
  ——	3β-hydroxy-12-oxoolean-28-oic acid methyl ester	108776-85-8	C31H50O4	486.736

反应信息

• 作为反应物：
  描述：

  (3β,12α) 3,12-dihydroxy-18β-olean-28-oic acid 28,13-lactone 在 氨 、 lithium 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 生成 齐墩果酸
  参考文献：
  名称：

  The chemical and biological potential of C ring modified triterpenoids

  摘要：

  A convenient and elegant route has been developed to separate the natural regioisomers triterpenoids ursolic acid (UA) and oleanolic acid (OA) as well as derivatives thereof. Eleven unknown derivatives of OA were designed, synthesized, and their cytotoxicity was investigated. Further sixteen compounds were prepared to correlate all compounds in a SAR study. It could be shown that C-ring modifications of OA and UA have only a moderate influence onto the cytotoxic activity of the compounds but a significant impact onto the ability to trigger apoptosis in ovarian cancer cells (cell line A2780). (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.11.025
• 作为产物：
  描述：

  齐墩果酸 在 间氯过氧苯甲酸 作用下， 以 氯仿 为溶剂， 以26.3 mg的产率得到(3β,12α) 3,12-dihydroxy-18β-olean-28-oic acid 28,13-lactone
  参考文献：
  名称：

  基于三氟甲磺酸铋（III）的齐墩果酸羟基-γ-内酯催化直接开放给Afford 12-Oxo-28-羧酸

  摘要：

  齐墩果酸羟基-γ-内酯的基于三氟甲磺酸铋（III）的催化直接打开以高收率在乙腈和二氯甲烷中提供了相应的在乙腈和二氯甲烷中的12-氧代-28-羧酸衍生物。的参与原位生成从铋（III），三氟甲磺酸是最有可能参与反应机理布朗斯台德酸物质。已通过1D和2D NMR技术对所得产物进行了完整的结构阐明。

  DOI：

  10.1002/adsc.201100155

文献信息

• Synthesis of novel heterocyclic oleanolic acid derivatives with improved antiproliferative activity in solid tumor cells
  作者：Ana S. Leal、Rui Wang、Jorge A. R. Salvador、Yongkui Jing

  DOI：10.1039/c3ob00011g

  日期：——

  A series of new oleanane imidazole carbamates, N-acylimidazoles or N-alkylimidazoles were synthesized, characterized and evaluated for their antiproliferative activity in AsPC-1 pancreatic cancer cells. Structure–activity relationship analysis revealed that the N-alkylimidazole 27 was the most active compound with apoptosis induction abilities correlated with upregulation of NOXA and downregulation of Bcl-xL. The antiproliferative activity of compound 27 was further tested in more solid tumor cell lines with IC50 values lower than 1 μM.

  合成了一系列新的齐墩果烷咪唑碳酸酯、N-酰基咪唑或N-烷基咪唑，并对其在AsPC-1胰腺癌细胞中的抗增殖活性进行了表征和评估。构效关系分析显示，N-烷基咪唑27是最具活性的化合物，其诱导凋亡的能力与NOXA的上调和Bcl-xL的下调相关。进一步测试了化合物27在更多实体瘤细胞系中的抗增殖活性，其IC50值低于1 μM。
• Partial synthesis of C-ring derivatives from oleanolic and maslinic acids. Formation of several triene systems by chemical and photochemical isomerization processes
  作者：Andrés Garcı́a-Granados、Pilar E López、Enrique Melguizo、Andrés Parra、Yolanda Simeó

  DOI：10.1016/j.tet.2003.12.023

  日期：2004.2

  Some triterpenic compounds modified in C-ring were semi-synthesised from oleanolic acid contained in the solid waste of olive-oil pressing. The corresponding esters of oleanolic and maslinic acids rendered products with a diene system, which led to oleantrienes resembling previtamin D2 by an electrocyclic reaction. Chemical and photochemical isomerization of these compounds yielded two different trienes

  从橄榄油压榨固体废物中所含的齐墩果酸半合成了一些在C环上改性的三萜类化合物。齐墩果酸和山lin酸的相应酯使产物具有二烯体系，其通过电环反应产生类似于维生素原D 2的油烯酮。这些化合物的化学和光化学异构化反应产生了两种不同的三烯，其结构与速甾醇和维生素D 2相似。
• Synthesis and Biological Evaluation of Oleanolic Acid Derivatives As Inhibitors of Protein Tyrosine Phosphatase 1B
  作者：Shan Qian、Haijiao Li、Yin Chen、Weiyu Zhang、Shengyong Yang、Yong Wu

  DOI：10.1021/np100064m

  日期：2010.11.29

  Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator in the process of insulin signaling and a promising drug target for diabetes and obesity. Derivatives of oleanolic acid were synthesized and evaluated as PTP1B inhibitors. Several derivatives exhibited moderate to good inhibitory activities against PTP1B, with 25f displaying the most promising inhibition (IC50 = 3.12 μM). Structure−activity

  蛋白酪氨酸磷酸酶1B（PTP1B）是胰岛素信号传导过程中的负调节剂，是糖尿病和肥胖症的有希望的药物靶标。合成齐墩果酸的衍生物并评价为PTP1B抑制剂。几种衍生物对PTP1B表现出中等至良好的抑制活性，其中25f表现出最有希望的抑制作用（IC 50 = 3.12μM）。这些衍生物的结构活性关系分析表明，A环和12-烯部分的完整性在保留PTP1B酶抑制活性中很重要。此外，亲水和酸性基团以及齐墩烯与酸部分之间的距离与PTP1B抑制活性有关。25f的可能绑定模式 通过分子对接模拟进行了探索。
• Efficient oxidation of oleanolic acid derivatives using magnesium bis(monoperoxyphthalate) hexahydrate (MMPP): A convenient 2-step procedure towards 12-oxo-28-carboxylic acid derivatives
  作者：Jorge A R Salvador、Vânia M Moreira、Rui M A Pinto、Ana S Leal、José A Paixão

  DOI：10.3762/bjoc.8.17

  日期：——

  straightforward and high yielding procedure to convert oleanolic acid derivatives into the corresponding delta-hydroxy-gamma-lactones, by using the convenient oxidizing agent magnesium bis(monoperoxyphthalate) hexahydrate (MMPP) in refluxing acetonitrile, is reported. In addition, a two-step procedure for the preparation of oleanolic 12-oxo-28-carboxylic acid derivatives directly from Delta(12)-oleananes

  报道了通过在回流乙腈中使用方便的氧化剂双（单过氧邻苯二甲酸酯）六水合物 (MMPP) 镁，将齐墩果酸衍生物转化为相应的 δ-羟基-γ-内酯的一种新的、直接且高产的方法。此外，直接从 Delta(12)-齐墩果烷制备齐墩果酸 12-氧代-28-羧酸衍生物的两步程序，无需中间后处理，并在两个步骤中保持相同的反应溶剂, 被描述为应用于 3,12-dioxoolean-28-oic 酸的合成。
• Gastroprotective and ulcer-healing activity of oleanolic acid derivatives: In vitro–in vivo relationships
  作者：Marianela Sánchez、Cristina Theoduloz、Guillermo Schmeda-Hirschmann、Iván Razmilic、Tania Yáñez、Jaime A. Rodríguez

  DOI：10.1016/j.lfs.2006.03.044

  日期：2006.8

  The triterpene oleanolic acid 1 and its semisynthetic derivatives 2-7 were assessed for gastroprotective and ulcer-healing effect using human epithelial gastric cells (AGS) and human lung fibroblasts (MRC-5). The ability of the compounds to protect the AGS cells against the damage induced by sodium taurocholate (NaT), to stimulate the cellular reduced glutathione (GSH) and prostaglandin E-2 content, to enhance AGS and MRC-5 cell proliferation and to scavenge superoxide anion in vitro was studied. The cytotoxicity of the compounds was assessed towards MRC-5 and AGS cells. In addition, the gastroprotective activity of the compounds was assessed in vivo using the HCl/EtOH-induced ulcer model in mice. All the assayed compounds displayed a significant reduction of AGS cells damage after incubation with NaT. None of the studied compounds was active as a superoxide anion scavenger nor stimulated the GSH content in AGS, cell cultures. Compounds 1, 2, 4 and 6 were able to increase the prostaglandin content in AGS cell cultures. Concerning the proliferation assays, a significant stimulating effect was observed for compounds 3 and 7 on AGS cells and for 1 and 7 on MRC-5 fibroblasts. Regarding cytotoxicity, derivatives 2, 4, 6 and 7 were less toxic than the parent compound oleanolic acid. Our results strongly support the predictive capacity of the in vitro assessment of gastroprotective activity allowing the reduction of experimental animals. (c) 2006 Elsevier Inc. All rights reserved.