11-hydroxymethyl-4,4a,6a,6b,8a,11,14b-heptamethyl-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-eicosahydropicene-3,14-diol | 77397-93-4

• 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-hydroxymethyl-4,4a,6a,6b,8a,11,14b-heptamethyl-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-eicosahydropicene-3,14-diol
• 英文别名: olean-12-en-3β,11ξ,30-triol；18β-olean-12-ene-3β,11,30-triol；11-hydroxymethyl-4,4,6a,6b,8a,11,14b-heptamethyl-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-eicosahydro-picene-3,14-diol；(3S,4aR,6aR,6bS,8aS,11S,12aR,14aR,14bS)-11-(hydroxymethyl)-4,4,6a,6b,8a,11,14b-heptamethyl-1,2,3,4a,5,6,7,8,9,10,12,12a,14,14a-tetradecahydropicene-3,14-diol
• CAS: 77397-93-4
• 化学式: C₃₀H₅₀O₃
• 分子量: 458.725
• InChiKey: LOBOMSGBFMNHBJ-GXNWASMWSA-N

物化性质

• 沸点：
  557.9±50.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  33
• 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：
  60.7
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  11-hydroxymethyl-4,4a,6a,6b,8a,11,14b-heptamethyl-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-eicosahydropicene-3,14-diol 在 palladium on activated charcoal 咪唑 、 4-二甲氨基吡啶 、 potassium permanganate 、 sodium dihydrogenphosphate 、 四丁基氟化铵 、 氢气 、 potassium carbonate 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 乙醇 、 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 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 生成 11-hydroxymethyl-4,4a,6a,6b,8a,11,14b-heptamethyl-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-eicosahydropicene-3,14-diol
  参考文献：
  名称：

  枯草芽孢杆菌ATCC 6633和巨大芽孢杆菌CGMCC 1.1741对甘草次酸衍生物的微生物转化。

  摘要：

  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

  DOI：

  10.1016/j.bmc.2020.115465

文献信息

• 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。
• Chemical modification of glycyrrhetinic acid in relation to the biological activities.
  作者：KUNIO TAKAHASHI、SHOJI SHIBATA、SHINGO YANO、MASATOSHI HARADA、HIROSHI SAITO、YASUSHI TAMURA、AKIRA KUMAGAI

  DOI：10.1248/cpb.28.3449

  日期：——

  Several modified derivatives of glycyrrhetinic acid were prepared for obtaining compounds which are devoid of aldosterone-like properties and retain or enhance the therapeutic activities of the mother compound. Among them, olean-12-en-3β, 30-diol showed antiallergic and antiulcerous activities without inhibition of Δ4-5α- and Δ4-5β-reductases of 3-keto-Δ4-steroids. This compound was prepared in a good yield from glycyrrhetinic acid by reduction with sodium bis (2-methoxyethoxy) aluminum hydride followed by catalytic hydrogenation of the intermediate with Pd-C.

  几种甘草酸的改性衍生物被制备出来，以获得不具醛固酮样特性的化合物，并保留或增强母体化合物的治疗活性。其中，olean-12-en-3β, 30-diol显示了抗过敏和抗溃疡活性，而不抑制3-酮-Δ4类固醇的Δ4-5α和Δ4-5β还原酶。该化合物由甘草酸通过与二甲氧基乙氧基铝氢化钠还原后，再用Pd-C催化加氢中间体制备，收率良好。
• Synthesis of hairpin siRNA using 18β-glycyrrhetinic acid derivative as a loop motif
  作者：Eun-Kyoung Bang、Byeang Hyean Kim

  DOI：10.1016/j.tetlet.2009.03.049

  日期：2009.5

  We synthesized a new phosphoramidite building block from 18 beta-glycyrrhetinic acid. This compound was introduced in the middle of the palindromic oligonucleotides and they formed hairpin structure. This 18 beta-glycyrrhetinic acid derivative excellently performed its role as hairpin loop. These hairpin ODNs had higher T-m values than the natural one and formed stable hairpin structure without any structural distortion. We found that stability of hairpin ODNs was changed according to the length of hairpin stem and modified hairpin ODNs, which had longer than seven base pair stem, were more stable than natural one based on T-m values. The shRNAs bearing similar modified loop were also synthesized. These modified shRNAs could suppress their target gene expression without losing their RNAi efficiency. (C) 2009 Elsevier Ltd. All rights reserved.