11-deoxoglycyrrhetic acid methyl ester acetate | 20475-98-3

• 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: 11-deoxoglycyrrhetic acid methyl ester acetate
• 英文别名: (2S,4aS,6aS,6bR,8aR,10S,12aR,12bR,14bR)-methyl 10-acetoxy-2,4a,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-2-carboxylate；3β-O-acetoxyolean-12-en-30-oic acid methyl ester；3β-Acetoxy-Δ¹²-oleanen-30-saeuremethylester；methyl 3β-acetoxy-18βH-olean-12-en-30-oate；3β-acetoxy-oleanen-(12)-oic acid-(30)-methyl ester；methyl 3β-acetoxy-18β-olean-12-en-30-oate；3β-Acetoxy-oleanen-(12)-saeure-(30)-methylester；methyl (2S,4aS,6aR,6aS,6bR,8aR,10S,12aR,14bR)-10-acetyloxy-2,4a,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-2-carboxylate
• CAS: 20475-98-3
• 化学式: C₃₃H₅₂O₄
• 分子量: 512.773
• InChiKey: KZTMPTOSZBKPSI-YBZWEUEASA-N

物化性质

• 熔点：
  263-265 °C
• 沸点：
  539.1±50.0 °C(predicted)
• 密度：
  1.07±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.4
• 重原子数：
  37
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  11-deoxoglycyrrhetic acid methyl ester acetate 在 selenium(IV) oxide 、 溶剂黄146 作用下， 生成 3β-acetoxy-oleanadien-(11.13(18))-oic acid-(30)-methyl ester
  参考文献：
  名称：

  Fire blight of pears in Israel: infection, prevalence, intensity and efficacy of management actions

  摘要：

  The Pear production area in Israel is 1500 ha, most of which (ca 1200 ha) is located in the northern part of the country. Fire blight (caused by the bacterium Erwinia amylovora (Burrill) Winslow et al.) was first observed in Israel in that region (in 1985) and the disease has prevailed there since then. In a comprehensive survey conducted in Israel in 1996-1999, data were collected and observations were made yearly in one-third to one-half of the pear production area. The aim was to document the prevalence and intensity of fire blight in commercial orchards and to use the data to evaluate the efficacy of management measures employed for its suppression, Regionwise, a severe fire blight epidemic developed in 1996, moderate epidemics developed in 1998 and 1999, and a mild epidemic developed in 1997. The intensity of fire blight in the preceding season in a specific orchard was more influential on current season severity in a season with a mild epidemic than in a season with a moderate epidemic. Analysis of disease onset records and weather data revealed that only a few (1-3) infection episodes occurred in individual orchards each year. Comparison of fire blight intensity in orchard-plots treated before green tip with copper hydroxide with nontreated plots revealed that the treatment had no effect on disease intensity during bloom. The efficacy of bactericide sprays applied during bloom was not related to the number of sprays applied but to the timing of spraying. Adequate control was achieved in orchard-plots sprayed soon before or after the occurrence of infection episodes.

  DOI：

  10.1007/bf02981831
• 作为产物：
  描述：

  3β-acetoxy-11-oxo-olean-12-en-30-oic acid methyl ester 在 盐酸 、 锌 作用下， 生成 11-deoxoglycyrrhetic acid methyl ester acetate
  参考文献：
  名称：

  新型甘草次酸衍生物的合成及生物活性

  摘要：

  不同类型恶性肿瘤的治疗方案是基于手术方法结合高剂量多化学疗法的使用。后者的一个严重缺陷是当代抗肿瘤剂对生物体的重要器官和系统的高毒性。相关的副作用会降低疗效，并且在某些情况下会限制抗肿瘤药物的使用。残留肿瘤克隆的问题仍未解决。在化疗中存活下来的肿瘤细胞显示出对多种药物的耐药性，并经常导致疾病以更严重的形式复发。因此，当务之急是寻找具有高治疗选择性和疗效的新型抗肿瘤药物。使用通过植物代谢物的合成转化获得的物质，尤其是那些已知能可靠地显示生物活性并且现在或将来可用作原料来源的药物是药物化学的一个重要趋势，旨在开发新的高效抗肿瘤剂。这些类型的化合物涉及五环三萜，其广泛的药理活性吸引并扩大了研究人员对这些化合物的兴趣 (1-5)。

  DOI：

  10.1134/s0012500810020011

文献信息

• Synthesis and Pro-Apoptotic Activity of Novel Glycyrrhetinic Acid Derivatives
  作者：Evgeniya B. Logashenko、Oksana V. Salomatina、A. V. Markov、Dina V. Korchagina、Nariman F. Salakhutdinov、Genrikh A. Tolstikov、Valentin V. Vlassov、Marina A. Zenkova

  DOI：10.1002/cbic.201000618

  日期：2011.3.21

  A new killer of cancer: Glycyrrhetinic acid derivatives were screened for their potential as inducers of human cancer cell death. Compound 1 displayed potent single‐agent activity at micromolar concentrations, and induced death in various human cancer cells. Further analysis indicated that cell death was caused by the intrinsic caspase‐dependent apoptosis pathway.

  新的癌症杀手：筛选甘草次酸衍生物作为人类癌细胞死亡诱导剂的潜力。化合物1在微摩尔浓度下表现出强大的单药活性，并在各种人类癌细胞中诱导死亡。进一步的分析表明，细胞死亡是由内在的半胱天冬酶依赖性细胞凋亡途径引起的。
• Oxidation of Licorice-Root Triterpene-Acid Derivatives by m-Chloroperbenzoic Acid
  作者：L. R. Mikhailova、A. S. Budaev、L. V. Spirikhin、L. A. Baltina

  DOI：10.1007/s10600-019-02619-5

  日期：2019.1

  12(13)-dien-30-oic, and 3β-O-acetoxy-18βH-olean-12-en-30-oic acids were oxidized by meta-chloroperbenzoic acid (m-CPBA) to produce methyl esters of 3β-O-acetoxy-12α,13α-epoxy-18β-oleanan-30-oic and 3β-O-acetoxy-18β-oleanan-12-on-30-oic acids in addition to 3β-hydroxy-12-oxo-18βH-olean-9(11)-en-30-oic and 3β-O-acetoxy-18β-oleanan-12-on-30-oic acids in 70–75% yields. The structures of the synthesized compounds

  3β-O-乙酰氧基-18βH-olean-12-en-30-oic、3β-羟基-9(11​​)、12(13)-dien-30-oic和3β-O-乙酰氧基-18βH-的甲酯olean-12-en-30-oic 酸被间氯过苯甲酸 (m-CPBA) 氧化生成 3β-O-acetoxy-12α,13α-epoxy-18β-oleanan-30-oic 和 3β-O 的甲酯-acetoxy-18β-oleanan-12-on-30-oic 酸以及 3β-hydroxy-12-oxo-18βH-olean-9(11​​)-en-30-oic 和 3β-O-acetoxy-18β-oleanan -12-on-30-油酸的产率为 70-75%。合成化合物的结构经PMR和13C NMR谱确证。
• Synthesis of methyl 2-cyano-3,12-dioxo-18β-olean-1,9(11)-dien-30-oate analogues to determine the active groups for inhibiting cell growth and inducing apoptosis in leukemia cells
  作者：Xiaojing Li、Yuetong Wang、Yuan Gao、Lei Li、Xin Guo、Dan Liu、Yongkui Jing、Linxiang Zhao

  DOI：10.1039/c4ob00703d

  日期：——

  Fourteen of the methyl 2-cyano-3,12-dioxo-18β-olean-1,9(11)-dien-30-oate (CDODO-Me-12, 10d) analogues with different structures of ring C were synthesized to determine the active groups for inhibiting cell growth and inducing apoptosis in human leukemia HL-60 cells. An unsaturated group in ring C was required to maintain the ability to inhibit cell growth and induce apoptosis. Compound 10e with 9(11),12-dien in ring C displayed comparable apoptosis induction ability to 10d associated with decreased levels of c-FLIP, but not Mcl-1 and XIAP. Compound 10e had decreased ability to deplete GSH compared to compound 10d. Compound 10e represents a new active compound acting through a different mechanism from that of compound 10d.

  合成了14种具有不同C环结构的2-氰基-3,12-二氧-18β-油烯-1,9(11)-二烯-30-酸甲酯(CDODO-Me-12，10d)类似物，以确定抑制人白血病HL-60细胞增殖和诱导凋亡的活性基团。C环中需要一个不饱和基团来维持抑制细胞增殖和诱导凋亡的能力。C环中具有9(11),12-二烯的化合物10e显示出了与10d相当的诱导凋亡能力，这与其降低了c-FLIP而非Mcl-1和XIAP的水平有关。与化合物10d相比，化合物10e的耗竭谷胱甘肽能力降低。化合物10e是一种通过不同于化合物10d的作用机制发挥活性的新型活性化合物。
• Synthesis of novel 2-cyano substituted glycyrrhetinic acid derivatives as inhibitors of cancer cells growth and NO production in LPS-activated J-774 cells
  作者：Oksana V. Salomatina、Andrey V. Markov、Evgeniya B. Logashenko、Dina V. Korchagina、Marina A. Zenkova、Nariman F. Salakhutdinov、Valentin V. Vlassov、Genrikh A. Tolstikov

  DOI：10.1016/j.bmc.2013.10.049

  日期：2014.1

  Here we report the synthesis and biological activity of new semi-synthetic derivatives of naturally occurring glycyrrhetinic acid bearing a 2-cyano-3-oxo-1-en moiety in the A-ring and double bonds and carbonyl groups in the C, D and E rings. Bioassays using murine macrophage-like and tumor cells show that compound 4, which differs from Soloxolone methyl by the absence of a 9(11)-double bond in the

  在这里，我们报告了天然存在的甘草次酸的新半合成衍生物的合成和生物活性，该衍生物在A环上带有2-cyano-3-oxo-1-en部分，在C，D和C中带有双键和羰基E环。使用鼠类巨噬细胞样细胞和肿瘤细胞进行的生物分析表明，化合物4与Soloxolone甲基的不同之处在于C环中不存在9（11）双键，因此对肿瘤细胞具有抗炎和抑制活性高选择性指数值。
• GLYCYRRHETINIC ACID DERIVATIVES AND METHODS OF USE THEREOF
  申请人：AbbVie Inc.

  公开号：US20140073700A1

  公开（公告）日：2014-03-13

  The present application relates to: (a) compounds of Formula (I): and salts thereof, wherein Y and Z are as defined in the specification; (b) compositions comprising such compounds and salts; and (c) methods of use of such compounds, salts, and compositions, particularly use for the treatment and prevention of diseases such as those associated with oxidative stress and inflammation.

  本申请涉及以下内容：(a) 公式(I)化合物及其盐，其中Y和Z如规范中定义；(b) 包含此类化合物和盐的组合物；以及(c) 使用此类化合物、盐和组合物的方法，尤其用于治疗和预防与氧化应激和炎症相关的疾病。