3β-acetoxy-11-oxo-18β-olean-12-en-30-oyl chloride | 30151-31-6

• 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-acetoxy-11-oxo-18β-olean-12-en-30-oyl chloride
• 英文别名: 3-O-acetyl-18βH-glycyrrhetyl chloride；3β-acetylglycyrrhetic acid chloroanhydride；3-O-acetylglycyrrhetic acid chloride；glycyrrhetinic acid chloride；3-acetylglycyrrhetinic acid chloride；(3β,18β,20β)-3-(acetyloxy)-11-oxoolean-12-en-29-oyl chloride；(3β,18β,20β)-3-(acetoxy)-11-oxo-olean-12-en-29-oyl chloride；3β-acetoxy-11-oxo-olean-12-en-30-oyl chloride；3-acetoxyglycyrrhetinic acid chloride；3-O-Acetylglycyrrhetinoyl chloride；[(3S,4aR,6aR,6bS,8aS,11S,12aR,14aR,14bS)-11-carbonochloridoyl-4,4,6a,6b,8a,11,14b-heptamethyl-14-oxo-2,3,4a,5,6,7,8,9,10,12,12a,14a-dodecahydro-1H-picen-3-yl] acetate
• CAS: 30151-31-6
• 化学式: C₃₂H₄₇ClO₄
• 分子量: 531.176
• InChiKey: DZFQWGGVBUZFSA-XWEVEMRCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8
• 重原子数：
  37
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  60.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3β-acetoxy-11-oxo-18β-olean-12-en-30-oyl chloride 在 sodium azide 作用下， 以 二氯甲烷 、 氯仿 、 丙酮 为溶剂， 反应 15.5h， 生成 N',N'-bis(2-hydroxyethyl)-N-[(3β,18β,20β)-3-(acetoxy)-11-oxo-30-norolean-12-en-20-yl]urea
  参考文献：
  名称：

  Synthesis of new glycyrrhetinic acid derived ring A azepanone, 29-urea and 29-hydroxamic acid derivatives as selective 11β-hydroxysteroid dehydrogenase 2 inhibitors

  摘要：

  Glycyrrhetinic acid, the metabolite of the natural product glycyrrhizin, is a well known nonselective inhibitor of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) type 1 and type 2. Whereas inhibition of 11 beta-HSD1 is currently under consideration for treatment of metabolic diseases, such as obesity and diabetes, 11 beta-HSD2 inhibitors may find therapeutic applications in chronic inflammatory diseases and certain forms of cancer. Recently, we published a series of hydroxamic acid derivatives of glycyrrhetinic acid showing high selectivity for 11 beta-HSD2. The most potent and selective compound is active against human 11 beta-HSD2 in the low nanomolar range with a 350-fold selectivity over human 11 beta-HSD1. Starting from the lead compounds glycyrrhetinic acid and the hydroxamic acid derivatives, novel triterpene type derivatives were synthesized and analyzed for their biological activity against overexpressed human 11 beta-HSD1 and 11 beta-HSD2 in cell lysates. Here we describe novel 29-urea- and 29-hydroxamic acid derivatives of glycyrrhetinic acid as well as derivatives with the Beckman rearrangement of the 3-oxime to a seven-membered ring, and the rearrangement of the C-ring from 11-keto-12-ene to 12-keto-9(11)-ene. The combination of modifications on different positions led to compounds comprising further improved selective inhibition of 11 beta-HSD2 in the lower nanomolar range with up to 3600-fold selectivity. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.02.005
• 作为产物：
  描述：

  甘草酸 在 吡啶 、 甲醇 、 氯化亚砜 、 硫酸 作用下， 以 二氯甲烷 为溶剂， 反应 72.0h， 生成 3β-acetoxy-11-oxo-18β-olean-12-en-30-oyl chloride
  参考文献：
  名称：

  甘草甜素作为选择性抗阿尔茨海默病药物的衍生化，分子对接和体外乙酰胆碱酯酶抑制活性。

  摘要：

  乙酰胆碱酯酶抑制剂（AChE-Is）可增加乙酰胆碱（ACh）的作用水平和作用持续时间；因此，减轻了阿尔茨海默氏病（AD）的症状。甘草甜素是甘草根中的主要活性化合物。它的糖苷配基，甘草次酸显示出几种有益的药理活性。该研究报告了一系列甘草次酸类似物AChE-Is的合成和筛选。制备了十四个衍生物，其中五个衍生物被记录为新的，即3-苯基氨基甲酰基-18β-甘草次酸（J9），3-乙酰基-18β-甘草次酸-30-苯胺（J10），3-乙酰基-18β -甘草次酸30-乙醇酰胺（J11），3-乙酰基18β-甘草次酸30-正丁酰胺（J12）和18β-甘草次酸30-异戊二烯酯（J14），以及九种已知衍生物（J1 - J8和J13）。化合物J12，J11，J0和J3表现出显着的AChE-1活性，IC 50值分别为3.43、5.39、6.27和8.68μM。这些结果与对接研究完全一致。活性化合物对正常细胞（WI-38）无细胞毒性。

  DOI：

  10.1080/14786419.2018.1462177

文献信息

• Novel triterpene derivatives
  申请人：onepharm Research & Development GmbH

  公开号：EP2228380A1

  公开（公告）日：2010-09-15

  The present invention encompasses novel triterpene compounds of general formula I wherein R3a R3b R11a R11b R31 and R32 are defined as in claim 1, which are suitable for the prevention and/or treatment of diseases mediated by 11β-HSD and the use thereof for preparing a medicament having the above-mentioned properties.

  本发明涵盖了一般式I的新型三萜化合物， 其中 R3a、R3b、R11a、R11b、R31和R32如权利要求1所定义，适用于预防和/或治疗由11β-HSD介导的疾病，并用于制备具有上述特性的药物。
• [EN] NOVEL TRITERPENE DERIVATIVES<br/>[FR] NOUVEAUX DÉRIVÉS TRITERPÉNIQUES
  申请人：ONEPHARM RES & DEV GMBH

  公开号：WO2012020019A1

  公开（公告）日：2012-02-16

  The present invention encompasses compounds of general formula (I) wherein R11a to R30 and X are defined as in claim 1, which are suitable for the treatment of and/or prevention of chronic inflammatory diseases, autoimmune diseases, skin diseases, bone diseases, metabolic diseases, infectious diseases and cancer.

  本发明涵盖了一般式（I）中R11a到R30和X的化合物，其中如权利要求书中所定义的，适用于治疗和/或预防慢性炎症性疾病、自身免疫疾病、皮肤疾病、骨疾病、代谢性疾病、传染病和癌症。
• Synthesis and Biological Evaluation of Novel Curcuminoid Derivatives
  作者：Ya-Kun Cao、Hui-Jing Li、Zhi-Fang Song、Yang Li、Qi-Yong Huai

  DOI：10.3390/molecules191016349

  日期：——

  Curcuminoids have been reported to possess multiple bioactivities, such as antioxidant, anticancer and anti-inflammatory properties. Three novel series of curcuminoid derivatives (11a–h, 15a–h and 19a–d) with enhanced bioactivity have been synthesized. Among the synthesized compounds, 11b exhibited the most significant activity with an MIC of 0.5 µM /mL against selected medically important Gram-positive

  据报道，类姜黄素具有多种生物活性，例如抗氧化、抗癌和抗炎特性。已经合成了三个具有增强生物活性的新型姜黄素衍生物系列（11a-h、15a-h 和 19a-d）。在合成的化合物中，11b 对选定的医学上重要的革兰氏阳性球菌（S. aureus 和 S. viridans）和革兰氏阴性杆菌（E.coli 和 E. cloacae）表现出最显着的活性，MIC 为 0.5 µM/mL . 这些衍生物在抗氧化试验中表现出显着的结果，其 IC50 比类姜黄素小 2.4 至 9.3 倍。关于对 Hep-G2、LX-2、SMMC7221 和 MDA-MB-231 的抗增殖活性，衍生物表现出比类姜黄素更强的作用，IC50 范围为 0.18 至 4.25 µM。
• Glycyrrhetinic acid and its analogs: A new class of antifilarial agents
  作者：Komal Kalani、Vikas Kushwaha、Richa Verma、P. Kalpana Murthy、S.K. Srivastava

  DOI：10.1016/j.bmcl.2013.02.115

  日期：2013.5

  program for antifilarial agents from Indian medicinal plants, the roots of G. glabra were chemically investigated, which resulted in the isolation and characterization of an antifilarial agent, glycyrrhetinic acid (GA, 1a) effective against microfilariae (mf) in vitro (LC100: 12.5 μM; IC50: 1.20 μM), but was inactive against adult worms. Further, GA (1a) was converted into six analogs (2a–7a) and their antifilarial

  尽管已从甘草中分离出许多化学物质，但仅对其化学意义进行了评估。作为我们从印度药用植物获得的抗丝虫剂药物发现计划的一部分，化学研究了G. glabra的根，从而分离并鉴定了对微丝aria虫（mf）有效的抗丝虫剂甘草次酸（GA，1a）。体外（LC100：12.5μM; IC 50：1.20μM ），但对成虫无活性。此外，GA（1a）被转化为六个类似物（2a – 7a）及其抗丝氨酸潜力进行了研究，通过研究利用MF和成虫的马来蝇（Brugia malayi）的体外活力和MTT降低试验。结果表明，在6种GA类似物中，苄基酰胺类似物（6a）分别杀死了25和50μM浓度的成虫和mf，并抑制了49％的成虫寄生虫MTT还原潜力。发现成人和mf的IC 50值分别为8.8和2.2μM。化合物的SI> 60。另一方面，辛酰胺类似物（7a）需要更高的浓度才能对寄生虫产生不利影响。最后，使用马来芽孢杆菌在体内评估了两
• Synthesis and Antiviral Activity of Amino-Acid Conjugates of Glycyrrhetic Acid
  作者：L. A. Baltina、M. V. Khudobko、L. R. Mikhailova、L. A. Baltina、V. A. Fedorova、Ya. A. Orshanskaya、V. V. Zarubaev、O. I. Kiselev

  DOI：10.1007/s10600-014-0990-0

  日期：2014.7

  Conjugates of glycyrrhetic acid (GLA) with amino acids (L-isoleucine, -leucine, -valine, and -phenylalanine) were synthesized by the acid-chloride method using methyl or tert-butyl esters of the acids. Tests in MDCK cell culture showed that the GLA conjugate with phenylalanine exhibited high antiviral activity against influenza A/H1N1/pdm09 virus (ED50 = 4.4 μg/mL, SI = 161).

  甘草次酸（GLA）与氨基酸（L-异亮氨酸、-亮氨酸、-缬氨酸和-苯丙氨酸）的共轭物通过酸氯化物法合成，使用酸的甲酯或叔丁酯作为原料。在MDCK细胞培养实验中，GLA与苯丙氨酸的共轭物显示出对甲型流感H1N1/pdm09病毒的高抗病毒活性（ED50 = 4.4 μg/mL，SI = 161）。