3Beta-乙酰氧基白桦酸 | 10376-50-8

• 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
• 中文名称: 3Beta-乙酰氧基白桦酸
• 英文名称: 3-O-acetylbetulinic acid
• 英文别名: 3β-3-(acetyloxy)lup-20(29)-en-28-oic acid；3β-acetoxylup-20(29)-en-28-oic acid；3-acetylbetulinic acid；3β-acetoxybetulinic acid；3β-acetyloxy-lup-20(29)-en-28-oic acid；(1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-acetoxy-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a] chrysene-3a-carboxylic acid；3β-acetoxy-20(29)-lupen-28-oic acid；3β-acetyl-betulinic acid；betulinic acid 3-O-acetate；acetylbetulinic acid；(1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-acetoxy-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-3aH-cyclopenta[a]chrysene-3a- carboxylic acid；3β-acetyloxylup-20(30)-en-28-oic acid；Acetobetulinic acid；(1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-acetyloxy-5a,5b,8,8,11a-pentamethyl-1-prop-1-en-2-yl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysene-3a-carboxylic acid
• CAS: 10376-50-8
• 化学式: C₃₂H₅₀O₄
• 分子量: 498.747
• InChiKey: ACWNTJJUZAIOLW-BWXYOZBYSA-N

物化性质

• 熔点：
  >265°C (dec.)
• 沸点：
  561.1±33.0 °C(Predicted)
• 密度：
  1.09±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（轻微）、甲醇（轻微、超声处理）

计算性质

• 辛醇/水分配系数(LogP)：
  8.8
• 重原子数：
  36
• 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：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3Beta-乙酰氧基白桦酸 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以88%的产率得到白桦脂酸
  参考文献：
  名称：

  A Concise Semi-Synthetic Approach to Betulinic Acid from Betulin

  摘要：

  Betulin was convert to betulinic acid using two different synthetic routes. The first approach involved an oxidation of betulin using Jones' reagent to betulonic acid and subsequent NaBH4 reduction to betulinic acid. The second approach involved steps utilizing different protecting groups on the alcohol functional groups of betulin and Jones' oxidation to circumvent the isomerization of the secondary alcohol of betulinic acid.

  DOI：

  10.1080/00397919708006099
• 作为产物：
  描述：

  白桦脂醇 在 氢氧化钾 、 jones reagent 作用下， 以 四氢呋喃 、 甲醇 、 丙酮 为溶剂， 反应 13.0h， 生成 3Beta-乙酰氧基白桦酸
  参考文献：
  名称：

  摘要：

  New derivatives of betulonic acid containing on C-28 fragments of amino acids or their methyl esters were prepared as potential biologically active agents.

  DOI：

  10.1023/a:1021621907515

文献信息

• [EN] C-3 NOVEL TRITERPENE WITH C-17 AMINE DERIVATIVES AS HIV INHIBITORS<br/>[FR] NOUVEAU TRITERPÈNE EN C3 ASSOCIÉ À DES DÉRIVÉS AMINÉS EN C17 POUR UTILISATION À DES FINS D'INHIBITION DU VIH
  申请人：HETERO LABS LTD

  公开号：WO2017149518A1

  公开（公告）日：2017-09-08

  The present invention relates to to C-3 novel triterpene with C-17 amine derivatives of formula (I); or pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, prodrugs, compositions or combination thereof, wherein R1, R2, R3, R4, R5 and 'n' are as defined herein. The present invention also relates to pharmaceutical compositions comprising compounds of formula (I) and process for preparing them, and their use for the treatment of viral diseases and particularly HIV mediated diseases.

  本发明涉及具有式(I)的C-17胺衍生物的C-3新型三萜，或其药学上可接受的盐、溶剂化合物、水合物、互变异构体、立体异构体、前药、组合物或它们的组合，其中R1、R2、R3、R4、R5和'n'如本文所定义。本发明还涉及包含式(I)化合物的药物组合物及其制备方法，以及它们用于治疗病毒性疾病，特别是HIV介导的疾病。
• Synthesis of three triterpene series and their activity against respiratory syncytial virus
  作者：Gloria N. Santos da Silva、Diana Monti Atik、Jheini L. Antunes Fernandes、Deise de Freitas do Nascimento、Tiago Fazolo、Ana Paula Duarte de Souza、Simone C. Baggio Gnoatto

  DOI：10.1002/ardp.201800108

  日期：2018.8

  without treatment were used as negative control. The triterpene esterification at the hydroxyl group resulted in 17 derivatives. The 3,28‐di‐O‐acetylbetulin derivative (1a) showed the best results for cell viability, and real‐time PCR amplification was performed for 1a treatment. Remarkably, one new anti‐hRSV prototype was obtained through an easy synthesis of BE, which shall represent an alternative for

  人类呼吸道合胞病毒 (hRSV) 是导致急性下呼吸道感染住院的主要原因，尤其是在婴儿和幼儿中，有时会导致致命病例。单克隆抗体帕利珠单抗是预防这种病毒的可用选择之一，目前有几个 hRSV 疫苗试验正在进行中。不幸的是，治疗 hRSV 感染的唯一药物选择是利巴韦林，可用于严重的高危病例。出于这个原因，需要新的药物，在这种情况下，三萜及其衍生物是有希望的替代品，因为它们中的许多已经显示出重要的抗病毒活性，例如 bevirimat。因此，我们报告了针对 hRSV 测试的三个系列的三萜（桦木 (BE)、桦木酸 (BA) 和熊果酸 (UA)）衍生物。这些衍生物是通过使用商业酸酐在简单且廉价的分步反应中合成的。对于抗病毒试验，A549 细胞被 hRSV 感染，在化合物或利巴韦林（阳性对照）处理 96 小时后，通过 MTT 试验测试细胞活力。DMSO、未感染的细胞和未经处理的感染细胞用作阴性对照。羟基处的三萜酯化产生了
• [EN] NOVEL BETULINIC ACID PROLINE DERIVATIVES AS HIV INHIBITORS<br/>[FR] NOUVEAUX DÉRIVÉS PROLINE DE L'ACIDE BÉTULINIQUE UTILISÉS COMME INHIBITEURS DU VIH
  申请人：HETERO RESEARCH FOUNDATION

  公开号：WO2014105926A1

  公开（公告）日：2014-07-03

  The invention relates to novel betulinic acid derivatives and related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases. These compounds are esterified in position 3 and are substituted in position 17 of the betulinic acid structure, via a linking group W, by a saturated 5-7 membered nitrogen-heterocycle.

  这项发明涉及新型苦药酸衍生物和相关化合物，以及用于治疗病毒性疾病特别是HIV介导疾病的药物组合物。这些化合物在苦药酸结构的3位酯化，并且在17位通过连接基团W被取代，取代基是饱和的5-7元氮杂环。
• Picolyl amides of betulinic acid as antitumor agents causing tumor cell apoptosis
  作者：Uladzimir Bildziukevich、Lucie Rárová、David Šaman、Zdeněk Wimmer

  DOI：10.1016/j.ejmech.2017.12.096

  日期：2018.2

  compared to normal cells with therapeutic index (TI) between 7 and 100 for compounds 3a and 3b. The therapeutic index (TI = 100) was calculated for human malignant melanoma cell line (G-361) versus normal human fibroblasts (BJ). The cytotoxicity of other target amides (3c and 6a–6c) revealed lower effects than 3a and 3b in the tested cancer cell lines.

  制备了一系列桦木酸的甲基吡啶甲酰胺（3a - 3c和6a - 6c），并进行了细胞毒性筛选测试。当获得并比较了3a - 3c和6a - 6c的细胞毒性数据时，结构-活性关系研究导致发现了依赖于目标酰胺中吡啶环的o-，m-和p-取代的生物活性差异。酰胺3b和3a表现出细胞毒性（在IC 50中给出）值）分别在G-361（分别为0.5±0.1μM和2.4±0.0μM），MCF7（分别为1.4±0.1μM和2.2±0.2μM），HeLa（分别为2.4±0.4μM和2.3±0.5μM）和CEM（分别为6.5±1.5μM和6.9±0.4μM）肿瘤细胞系，在正常人成纤维细胞（BJ）中显示出较弱的作用。确定针对所有测试癌细胞的选择性，并将其与化合物3a和3b的治疗指数（TI）在7至100之间的正常细胞进行比较。计算人恶性黑色素瘤细胞系（G-361）与正常人成纤维细胞（BJ）的治疗指数（TI = 100 ）。其他目标酰胺（3c和6a
• Anticancer Activity of 3-<i>O</i>-Acylated Betulinic Acid Derivatives Obtained by Enzymatic Synthesis
  作者：Faujan Bin H. AHMAD、Mansour GHAFFARI MOGHADDAM、Mahiran BASRI、Mohd Basyaruddin ABDUL RAHMAN

  DOI：10.1271/bbb.90917

  日期：2010.5.23

  An easy and efficient strategy to prepare betulinic acid esters with various anhydrides was used by the enzymatic synthesis method. It involves lipase-catalyzed acylation of betulinic acid with anhydrides as acylating agents in organic solvent. Lipase from Candida antarctica immobilized on an acrylic resin (Novozym 435) was employed as a biocatalyst. Several 3-O-acyl-betulinic acid derivatives were successfully obtained by this procedure. The anticancer activity of betulinic acid and its 3-O-acylated derivatives were then evaluated in vitro against human lung carcinoma (A549) and human ovarian (CAOV3) cancer cell lines. 3-O-glutaryl-betulinic acid, 3-O-acetyl-betulinic acid, and 3-O-succinyl-betulinic acid showed IC50<10 μg/ml against A549 cancer cell line tested and showed better cytotoxicity than betulinic acid. In an ovarian cancer cell line, all betulinic acid derivatives prepared showed weaker cytotoxicity than betulinic acid.

  一种简便高效的策略通过酶合成方法制备了白桦酸的各种酐酯。该方法涉及在有机溶剂中使用酐作为酰化剂，通过脂肪酶催化白桦酸的酰化反应。采用了固定在丙烯酸树脂上的南极假丝酵母脂肪酶（Novozym 435）作为生物催化剂。通过这一步骤成功获得了几种3-O-酰基白桦酸衍生物。随后，评估了白桦酸及其3-O-酰化衍生物对人肺腺癌（A549）和人卵巢癌（CAOV3）细胞系的体外抗癌活性。3-O-戊二酰白桦酸、3-O-乙酰白桦酸和3-O-琥珀酰白桦酸对A549癌细胞系的IC50值小于10微克/毫升，并且显示出比白桦酸更强的细胞毒性。在卵巢癌细胞系中，所有制备的白桦酸衍生物的细胞毒性均弱于白桦酸。