18β-olean-12-ene-3β,30-diol | 6813-59-8

• 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: 18β-olean-12-ene-3β,30-diol
• 英文别名: deoxoglycyrrhetol；11-deoxoglycyrrhetol；3β,30-Dihydroxy-Δ¹²-oleanen；(3S,4aR,6aR,6bS,8aS,11S,12aR,14aR,14bR)-11-(hydroxymethyl)-4,4,6a,6b,8a,11,14b-heptamethyl-1,2,3,4a,5,6,7,8,9,10,12,12a,14,14a-tetradecahydropicen-3-ol
• CAS: 6813-59-8
• 化学式: C₃₀H₅₀O₂
• 分子量: 442.726
• InChiKey: OYONPFUYHNGECE-UBWAPJCPSA-N

物化性质

• 熔点：
  240-241 °C
• 沸点：
  524.8±50.0 °C(Predicted)
• 密度：
  1.05±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.6
• 重原子数：
  32
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  18β-olean-12-ene-3β,30-diol 在 咪唑 、 4-二甲氨基吡啶 、 potassium permanganate 、 sodium dihydrogenphosphate 、 四丁基氟化铵 、 potassium carbonate 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 24.0h， 生成 11-脱氧-18beta-甘草亭酸
  参考文献：
  名称：

  Synthesis of new glycyrrhetinic acid (GA) derivatives and their effects on tyrosinase activity

  摘要：

  To synthesize glycyrrhetinic acid (GA) derivatives (3, 4, 5, 10, 13, 14, 15, and 16), we first removed the ketonic group in the C-11 position, and the carboxylic function at the C-30 position was kept intact, reduced to an alcohol, or transformed to an aldehyde corresponding derivatives 10 and 13. Glycyrrhetinic acid (GA) derivatives (3, 4, 5, 15, and 16) were coupled with 4-amino piperpyridine derivatives (12 and 14) and 4-fluorobenzyl bromide at C-30 carboxylic acid position of glycyrrhetinic acid. In subsequent tyrosinase assays, we found that GA derivatives 4, 5, and 16 were not active at early time points, but strongly inhibited tyrosinase activity at late time points. Of the GA derivatives examined, derivative 5 was most active, with an IC50 value of 50 muM after 2 h reaction. IC50 values of derivatives 4 and 16 were 120 and 170 muM respectively. Further kinetic data indicated that these derivatives are slow-binding inhibitors of tyrosinase. The time-dependent inhibition was reversed when vitamin C or kojic acid was used, that is, both compounds showed active inhibition at early time points. These results suggest that GA derivatives are much more stable than vitamin C or kojic acid, although their intrinsic inhibitory potentials are relatively low. Higher stability and activity suggest that GA derivative 5 might be a useful candidate for skin whitening. (C) 2003 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2003.09.046
• 作为产物：
  描述：

  甘草次酸 在 palladium on activated charcoal 氢气 、 碳酸氢钠 、 红铝 作用下， 以 四氢呋喃 、 乙醇 、 甲苯 为溶剂， 反应 1.0h， 生成 18β-olean-12-ene-3β,30-diol
  参考文献：
  名称：

  Chemical modification of glycyrrhetinic acid in relation to the biological activities.

  摘要：

  18β-烯-12-烯-3β, 30-醇（去氧甘草醇）（4a）的制备旨在消除甘草酸（1b）的副作用假性醛固酮症，这是甘草皂苷甘草苷（1a）的薯蓣皂苷，同时保持或增强其治疗活性。通过用NaAlH2-(OCH2CH2OCH3)2还原1b的11-酮和30-羧基，获得了烯-12-烯-3β, 11β, 30-三醇（9）和烯-12-烯-3β, 11α, 30-三醇（10）。用Pd-C作为催化剂对9和10进行催化氢化反应，最终产率为80%得到了4a。用浓盐酸处理9时，生成了18β-烯-9（11）-12-烯-3β, 30-醇（11a），而10则生成了烯-11, 13（18）-烯-3β, 30-醇（12a）。制备了4a、11a和12a的单-和双-β-羧基-丙酰基及单-和双-邻-苯二甲酰基酯，以增强其亲水性。与1b引起的假性醛固酮症不同，在4a的情况下未观察到在肝脏中对皮质类固醇的5β, Δ4-还原酶的竞争抑制。化合物4a、11a和12a及其β-羧基丙酰基和邻-苯二甲酰基酯在药理学上进行了研究，显示出抗溃疡生成、抗过敏和抗炎活性。

  DOI：

  10.1248/cpb.35.1910

文献信息

• Microbial transformation of glycyrrhetinic acid derivatives by Bacillus subtilis ATCC 6633 and Bacillus megaterium CGMCC 1.1741
  作者：Pingping Shen、Jian Zhang、Yuyuan Zhu、Wei Wang、Boyang Yu、Weiwei Wang

  DOI：10.1016/j.bmc.2020.115465

  日期：2020.6

  ATCC 6633 and Bacillus megaterium CGMCC 1.1741. Their structures were identified on the basis of extensive spectroscopic methods and nine of them were found for the first time. Two main types of reactions, regio- and stereo-selective hydroxylation and glycosylation, especially in the unactivated C-H bonds including C-11, C-19 and C-27, were observed in the biotransformation process, which greatly expand

  甘草次酸（GA）是甘草根的主要生物活性五环三萜糖苷配基，已知在抗溃疡，抗抑郁，抗炎和抗过敏方面起着至关重要的作用。在这项研究中，我们通过一系列化学反应半合成了五种GA衍生物。它们被选作生物转化的底物，并被枯草芽孢杆菌ATCC 6633和巨大芽孢杆菌CGMCC 1.1741产生13种代谢物。根据广泛的光谱学方法鉴定了它们的结构，并且首次发现了其中的九种。在生物转化过程中观察到两种主要类型的反应，区域和立体选择性羟基化和糖基化，特别是在未激活的CH键中，包括C-11，C-19和C-27，大大扩展了GA的化学多样性衍生品。测试了所有化合物对脂多糖（LPS）刺激的RAW 264.7细胞中一氧化氮（NO）生成的抑制作用。其中，olean-12-ene-3β，7β，15α，19α，30-pentol（16）和olean-12-ene-3β，7β，15α，27,30-pentol（17）对IC50表现出明显的抑制作用值分别为0
• Synthesis and in Vitro Antioxidant Activity of Glycyrrhetinic Acid Derivatives Tested with the Cytochrome P450/NADPH System
  作者：Mourboul Ablise、Brigitte Leininger-Muller、Choi Dal Wong、Gérard Siest、Vincent Loppinet、Sophie Visvikis

  DOI：10.1248/cpb.52.1436

  日期：——

  Five glycyrrhetinic acid (Ib) derivatives have been synthesized to try to improve the antioxidant activity. Their in vitro antioxidant activities were studied using a cytochrome P450/NADPH reductase system from rat liver microsomes. The generation of microsomal free radicals was followed by oxidation of the DCFH-DA probe, while evaluating the capacity to inhibit reactive oxygen species (ROS) formation. Two hydroxylated derivatives, 18β-olean-12-ene-3β,11α,30-triol (II) and 18β-olean-12-ene-3β,11β,30-triol (IV), exhibited strong antioxidant activities. At a concentration of 1.0 mg/ml, these derivatives inhibited ROS formation by 50% and 51%, respectively. Moreover, two homo- and heterocyclic diene derivatives, 18β-olean-11,13(18)-diene-3β,30-diol (III) and 18β-olean-9(11),12-diene-3β,30-diol (V), were also effective in ROS-scavenging activity (inhibition of 41% and 44% of ROS activity, respectively). In the same conditions, the lead compound (Ib) and the reference vitamin E inhibited ROS activity by 31% and 32%, respectively. Our results suggest that the chemical reduction of the 11-keto and 30-carboxyl groups into hydroxyl function (example, II, IV) can increase the antioxidant activity of Ib significantly. In view of these results, our study represents a further approach to the development of potential therapeutic agents from Ib derivatives for use in pathologic events in which, free radical damage could be involved.

  为了提高抗氧化活性，我们合成了五种甘草次酸（Ib）衍生物。我们利用大鼠肝脏微粒体的细胞色素 P450/NADPH 还原酶系统研究了它们的体外抗氧化活性。微粒体自由基的生成是通过 DCFH-DA 探针的氧化进行的，同时还评估了抑制活性氧（ROS）形成的能力。18β-olean-12-ene-3β,11α,30 三醇（II）和 18β-olean-12-ene-3β,11β,30 三醇（IV）这两种羟基化衍生物表现出很强的抗氧化活性。在 1.0 毫克/毫升的浓度下，这些衍生物对 ROS 形成的抑制率分别为 50%和 51%。此外，18β-烯-11,13(18)-二烯-3β,30-二醇（III）和 18β-烯-9(11),12-二烯-3β,30-二醇（V）这两种同环和杂环二烯衍生物也具有有效的 ROS 清除活性（分别抑制了 41% 和 44% 的 ROS 活性）。在相同条件下，先导化合物（Ib）和参考维生素 E 对 ROS 活性的抑制率分别为 31% 和 32%。我们的研究结果表明，将 11-酮基和 30-羧基化学还原成羟基功能（例如，II、IV）可以显著提高 Ib 的抗氧化活性。鉴于这些结果，我们的研究为开发 Ib 衍生物的潜在治疗药物提供了进一步的思路，这些药物可用于可能涉及自由基损伤的病理事件。
• Synthesis and Antiproliferative Activity of Novel Heterocyclic Glycyrrhetinic Acid Derivatives
  作者：Daniela Alho、Jorge Salvador、Marta Cascante、Silvia Marin

  DOI：10.3390/molecules24040766

  日期：——

  A new series of glycyrrhetinic acid derivatives has been synthesized via the introduction of different heterocyclic rings conjugated with an α,β-unsaturated ketone in its ring A. These new compounds were screened for their antiproliferative activity in a panel of nine human cancer cell lines. Compound 10 was the most active derivative, with an IC50 of 1.1 µM on Jurkat cells, which is 96-fold more potent

  通过在其环A中引入与α，β-不饱和酮共轭的不同杂环，合成了一系列新的甘草次酸衍生物。在9种人类癌细胞系中筛选了这些新化合物的抗增殖活性。化合物10是活性最高的衍生物，在Jurkat细胞上的IC50为1.1 µM，效力比甘草次酸高96倍，对癌细胞系的选择性高4倍。在Jurkat细胞中进行的进一步生物学研究表明，化合物10是有效激活内在和外在途径的凋亡诱导剂。
• Synthesis and anti-influenza virus evaluation of triterpene-sialic acid conjugates
  作者：Mitsuru Tsuji、Nongluk Sriwilaijaroen、Hideo Inoue、Kazuhiko Miki、Kaoru Kinoshita、Kiyotaka Koyama、Kimio Furuhata、Yasuo Suzuki、Kunio Takahashi

  DOI：10.1016/j.bmc.2017.09.038

  日期：2018.1

  new non-natural glycosides with sialic acid conjugates and their biological activities. We report the synthesis of eleven non-natural occurring glycosides, which are triterpene (glycyrrhetinic acid and its derivatives)-sialic acid conjugates, and their inhibitory activities against influenza virus sialidases and influenza virus multiplication in MDCK host cells. Deoxoglycyrrhetol-sialic acid conjugates

  我们对具有唾液酸缀合物的新型非天然糖苷及其生物学活性感兴趣。我们报告了十一种非天然糖苷的合成，它们是三萜（甘草次酸及其衍生物）-唾液酸缀合物，以及它们对流感病毒唾液酸酶和MDCK宿主细胞中流感病毒繁殖的抑制活性。Deoxoglycyrrhetol-唾液酸结合物（6d和6e）和齐墩果酸-唾液酸结合物（7d和7e）显示出对三种亚型流感病毒唾液酸酶的强抑制活性。这四种化合物（6d，6e，7d和7e）对流感病毒的增殖表现出明显的抑制作用，但对MDCK宿主细胞的存活没有抑制作用。
• Folate Deficiency In Vitro Induces Uracil Misincorporation and DNA Hypomethylation and Inhibits DNA Excision Repair in Immortalized Normal Human Colon Epithelial Cells
  作者：Susan J. Duthie、Sabrina Narayanan、Stephanie Blum、Lynn Pirie、Gillian M. Brand

  DOI：10.1207/s15327914nc372_18

  日期：2000.7

  Epidemiological studies have indicated that folic acid protects against a variety of cancers, particularly cancer of the colorectum. Folate is essential for efficient DNA synthesis and repair. Moreover folate can affect cellular S-adenosylmethionine levels, which regulate DNA methylation and control gene expression. We have investigated the mechanisms through which folate affects DNA stability in immortalized normal human colonocytes (HCEC). DNA strand breakage, uracil misincorporation, and DNA repair, in response to oxidative and alkylation damage, were determined in folate-sufficient and folate-deficient colonocytes by single cell gel electrophoresis. In addition, methyl incorporation into genomic DNA was measured using the bacterial enzyme Sss1 methylase. Cultured human colonocyte DNA contained endogenous strand breaks and uracil. Folate deficiency significantly increased strand breakage and uracil misincorporation in these cells. This negative effect on DNA stability was concentration dependent at levels usually found in human plasma (1-10 ng/ml). DNA methylation was decreased in HCEC grown in the absence of folate. Conversely, hypomethylation was nor concentration dependent. Folate deficiency impaired the ability of HCEC to repair oxidative and alkylation damage. These results demonstrate that folic acid modulates DNA repair DNA strand breakage, and uracil misincorporation in immortalized human colonocytes and that folate deficiency substantially decreases DNA stability in these cells.