乌宋酸甲酯 | 32208-45-0

• 物质功能分类: 生物化工 - 提取物 - 植物提取物
• 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
• 中文名称: 乌宋酸甲酯
• 英文名称: methyl (3β)-3-hydroxyurs-12-en-28-oate
• 英文别名: ursolic acid methyl ester；methyl ursolate；methyl 3β-hydroxy-urs-12-en-28-oate；3β-hydroxy-urs-12-en-28-oic acid methyl ester；methyl (1S,2R,4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-10-hydroxy-1,2,6a,6b,9,9,12a-heptamethyl-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxylate
• CAS: 32208-45-0
• 化学式: C₃₁H₅₀O₃
• 分子量: 470.736
• InChiKey: YCBSMEKEDOHEQI-QHQGJMPNSA-N

物化性质

• 熔点：
  286°C
• 沸点：
  529.2±50.0 °C(Predicted)
• 密度：
  1.06±0.1 g/cm3(Predicted)
• LogP：
  9.470 (est)

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  34
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

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
  熊果酸	ursolic acid	77-52-1	C30H48O3	456.709
  ——	methyl 3-acetylursolate	990-89-6	C33H52O4	512.773
  3-Keto-熊果酸-28-甲酯	methyl ursonate	989-72-0	C31H48O3	468.72
  熊果酸乙酸酯	(3β)-3-acetoxy-urs-12-en-28-carboxylic acid	7372-30-7	C32H50O4	498.747

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	3α-hydroxyurs-12-en-28-oic acid methyl ester	915-32-2	C31H50O3	470.736
  科罗索酸甲酯	methyl corosolate	4518-70-1	C31H50O4	486.736
  ——	methyl 2α,3α-dihydroxyurs-12-en-28-oate	52213-28-2	C31H50O4	486.736
  熊果酸	ursolic acid	77-52-1	C30H48O3	456.709
  ——	methyl 3-acetylursolate	990-89-6	C33H52O4	512.773
  ——	3-hydroxy-11-oxo-urs-12-en-28-oic acid methyl ester	132915-43-6	C31H48O4	484.72
  3-Keto-熊果酸-28-甲酯	methyl ursonate	989-72-0	C31H48O3	468.72
  ——	methyl 3β-O-carboxypropionylurs-12-ene-28-oate	——	C35H54O6	570.81
  ——	3-oxoursa-1,12-dien-28-oic acid methyl ester	272107-91-2	C31H46O3	466.704
  ——	methyl 3β-[(aminosulfonyl)oxy]urs-12-en-28-oate	——	C31H51NO5S	549.816

反应信息

• 作为反应物：
  描述：

  乌宋酸甲酯 在 lithium 作用下， 以 乙二胺 为溶剂， 反应 4.0h， 以70%的产率得到熊果酸
  参考文献：
  名称：

  Sengupta, Pasupati; Sen, Manju; Das, Saktipada, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1980, vol. 19, # 8, p. 721 - 722

  摘要：

  DOI：
• 作为产物：
  描述：

  熊果酸 在 吡啶 、 4-二甲氨基吡啶 、 水 、 potassium carbonate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 乌宋酸甲酯
  参考文献：
  名称：

  SENP1抑制剂熊果酸衍生物的发现及放射增敏研究

  摘要：

  SUMO化和去SUMO化在DNA损伤反应和放疗抵抗的形成中发挥着重要作用。 SENP1是催化去SUMO化修饰的主要特异性异肽酶。抑制 SENP1 会上调癌细胞的放射敏感性，使其成为放射增敏的有希望的靶标。在此，基于熊果酸（UA）的结构，总共设计并合成了53个五环三萜衍生物作为SENP1抑制剂。十种衍生物表现出比UA更好的SENP1抑制活性，并讨论了初步的构效关系。大多数UA衍生物的细胞毒性较低，其中化合物36的放射增敏活性最好， SER值为1.45。这是第一项开发小分子 SENP1 抑制剂作为放射增敏剂的研究。

  DOI：

  10.1016/j.ejmech.2021.113918

文献信息

• Structure-dependent inhibition of bladder and pancreatic cancer cell growth by 2-substituted glycyrrhetinic and ursolic acid derivatives
  作者：Gayathri Chadalapaka、Indira Jutooru、Alan McAlees、Tom Stefanac、Stephen Safe

  DOI：10.1016/j.bmcl.2008.03.031

  日期：2008.4

  Derivatives of oleanolic acid, ursolic acid and glycyrrhetinic acid substituted with electron-withdrawing groups at the 2-position in the A-ring which also contains a 1-en-3-one structure are potent inhibitors of cancer cell growth. In this study, we have compared the effects of several 2-substituted analogs of triterpenoid acid methyl esters derived from ursolic and glycyrrhetinic acid on proliferation

  齐墩果酸、熊果酸和甘草次酸的衍生物在 A 环的 2 位被吸电子基团取代，其中也包含 1-en-3-one 结构，是癌细胞生长的有效抑制剂。在这项研究中，我们比较了几种衍生自熊果酸和甘草次酸的三萜酸甲酯的 2-取代类似物对 KU7 和 253JB-V 膀胱以及 Panc-1 和 Panc-28 胰腺癌细胞增殖的影响。结果表明，2-氰基和2-三氟甲基衍生物是活性最强的化合物。具有包含 9(11)-en-12-one 结构的重排 C 环的甘草次酸衍生物通常比相应的 12-en-11-one 异构体更具活性。然而，
• 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。
• Inhibitory Effects of Constituents from Cynomorium songaricum and Related Triterpene Derivatives on HIV-1 Protease.
  作者：Chaomei MA、Norio NAKAMURA、Hirotsugu MIYASHIRO、Masao HATTORI、Kunitada SHIMOTOHNO

  DOI：10.1248/cpb.47.141

  日期：——

  From CH2Cl2 and MeOH extracts of the stems of Cynomorium songaricum RUPR. (Cynomoriaceae), ursolic acid and its hydrogen malonate were isolated as inhibitors of human immunodeficiency virus type 1 (HIV-1) protease, with 50% inhibitory concentrations (IC50) of 8 and 6 μM, respectively. Amongst various synthesized dicarboxylic acid hemiesters of related triterpenes, inhibitory activity tended to increase in the order of oxalyl, malonyl, succinyl and glutaryl hemiesters, for triterpenes such as ursolic acid, oleanolic acid and betulinic acid. The most potent inhibition was observed for the glutaryl hemiesters, with an IC50 of 4 μM.From the water extract of the stems of C. songaricum, flavan-3-ol polymers, consisting of epicatechin as their extender flavan units, were also found to be potent inhibitory principles against HIV-1 protease.

  从锁阳（Cynomorium songaricum RUPR.）茎的CH2Cl2和MeOH提取物中，分离得到了熊果酸及其丙二酸氢化物，它们是人类免疫缺陷病毒1型（HIV-1）蛋白酶的抑制剂，其半数抑制浓度（IC50）分别为8和6微摩尔。在合成的各种相关三萜二羧酸半酯中，对于熊果酸、齐墩果酸和白桦脂酸等三萜类化合物，抑制活性倾向于按草酰、丙二酰、琥珀酰和戊二酰半酯的顺序增加。其中，戊二酰半酯显示出最强的抑制作用，IC50为4微摩尔。从锁阳茎的水提取物中，还发现了由表儿茶素构成扩展单元的黄烷-3-醇聚合物，它们也是HIV-1蛋白酶的强效抑制剂。
• Synthesis and anti-cancer activity of some novel C-17 analogs of ursolic and oleanolic acids
  作者：Uppuluri V. Mallavadhani、Anita Mahapatra、Banita Pattnaik、Nagireddy Vanga、Nitasha Suri、Ajit K. Saxena

  DOI：10.1007/s00044-012-0106-y

  日期：2013.3

  A series of seventeen novel analogs of ursolic and oleanolic acid were synthesized (60–98 %), and evaluated for their anti-cancer potential against a panel of eight human cancer cell lines. Compounds (3–10) showed comparable or better activities than their respective parent compounds against SiHa and HeLa (Cervix), A-549 (Lung), and IMR-32 (Neuroblastoma) cancer cell lines. Significantly, among the

  合成了一系列17种新颖的熊果酸和齐墩果酸类似物（60-98％），并评估了它们对八种人类癌细胞系的抗癌潜力。化合物（3–10）对SiHa和HeLa（宫颈），A-549（肺）和IMR-32（神经母细胞瘤）癌细胞的活性比其各自的母体化合物更好或更高。值得注意的是，在溴代烷基酯中（11-19），化合物13在10μM浓度下对白血病THP-1细胞系显示出有希望的抗癌活性。在这个系列中，有趣的是，链长的增加对活性有不利影响。
• Chemical Phenotypes of the hmg1 and hmg2 Mutants of Arabidopsis Demonstrate the In-planta Role of HMG-CoA Reductase in Triterpene Biosynthesis
  作者：Kiyoshi Ohyama、Masashi Suzuki、Kazuo Masuda、Shigeo Yoshida、Toshiya Muranaka

  DOI：10.1248/cpb.55.1518

  日期：——

  Plants produce a wide variety of cyclic triterpenes, such as sterols and triterpenoids, which are the major products of the mevalonate (MVA) pathway. It is important to understand the physiological functions of HMG-CoA reductase (HMGR) because HMGR is the rate-limiting enzyme in the MVA pathway. We have previously isolated Arabidopsis mutants in HMG1 and HMG2. Although the biochemical function of HMGR2 has been thought to be almost equal to that of HMGR1, based on similarities in their sequences, the phenotypes of mutants in these genes are quite different. Whereas hmg2 shows no abnormal phenotype under normal growth conditions, hmg1 shows pleiotropic phenotypes, including dwarfing, early senescence, and male sterility. We previously postulated that the 50% decrease in the sterol content of hmg1, as compared to that in the wild type, was a cause of these phenotypes,1) but comprehensive triterpene profiles of these mutants had not yet been determined. Here, we present the triterpene profiles of hmg1 and hmg2. In contrast to hmg1, hmg2 showed a sterol content 15% lower than that of the wild type. A precise triterpenoid quantification using synthesized deuterated compounds of β-amyrin (1), α-amyrin (2), and lupeol (3) showed that the levels of triterpenoids in hmg1 and hmg2 were 65% and 25% lower than in the wild type (WT), respectively. These results demonstrate that HMGR2 as well as HMGR1 is responsible for the biosynthesis of triterpenes in spite of the lack of visible phenotypes in hmg2.

  植物产生多种环状三萜，如固醇和三萜类化合物，这些是梅瓦龙酸（MVA）途径的主要产物。了解HMG-CoA还原酶（HMGR）的生理功能非常重要，因为HMGR是MVA途径中的限速酶。我们之前已经分离出阿拉伯芥中HMG1和HMG2的突变体。虽然基于它们序列的相似性，HMGR2的生化功能被认为几乎与HMGR1相同，但这些基因突变体的表型却大相径庭。hmg2在正常生长条件下没有显示出异常表型，而hmg1则表现出多重表型，包括矮小、早衰和雄性不育。我们之前推测，hmg1的固醇含量比野生型降低50%是这些表型的原因之一，但这些突变体的全面三萜谱尚未确定。在这里，我们呈现hmg1和hmg2的三萜谱。与hmg1相比，hmg2的固醇含量比野生型低15%。使用合成的重氢化合物β-氨瑞烯（1）、α-氨瑞烯（2）和露蓉醇（3）进行的精确三萜类化合物定量显示，hmg1和hmg2中的三萜类化合物水平分别比野生型低65%和25%。这些结果表明，虽然hmg2缺乏明显的表型，但HMGR2和HMGR1均负责三萜的生物合成。

表征谱图