4-{[(3β)-28-(benzyloxy)-28-oxolup-20(29)-en-3-yl]oxy}-4-oxobutanoic acid | 1016893-62-1

• 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: 4-{[(3β)-28-(benzyloxy)-28-oxolup-20(29)-en-3-yl]oxy}-4-oxobutanoic acid
• 英文别名: benzyl betulinate hemisuccinate
• CAS: 1016893-62-1
• 化学式: C₄₁H₅₈O₆
• 分子量: 646.908
• InChiKey: PZGURIMKWNPYBN-CNEDUANUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.16
• 重原子数：
  47.0
• 可旋转键数：
  8.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  89.9
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  4-{[(3β)-28-(benzyloxy)-28-oxolup-20(29)-en-3-yl]oxy}-4-oxobutanoic acid 在 palladium 10% on activated carbon 1,4-环己二烯 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 22.0h， 以91%的产率得到3-O-succinyl betulinic acid
  参考文献：
  名称：

  WO2008/37226

  摘要：

  公开号：
• 作为产物：
  描述：

  白桦脂酸 在 4-二甲氨基吡啶 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 4-{[(3β)-28-(benzyloxy)-28-oxolup-20(29)-en-3-yl]oxy}-4-oxobutanoic acid
  参考文献：
  名称：

  桦木酸-氮杂环衍生物：设计、合成和体外抗肿瘤评价

  摘要：

  桦木酸（BA）是五环三萜类化合物家族的明星成员，在抗肿瘤药物开发方面具有广阔的前景。为了开发新的抗肿瘤候选物，除了四种中间体外，还合成了 21 种 BA-氮杂环衍生物，其中 23 种是首次报道的。此外，通过标准甲基噻唑四唑 (MTT) 测定法筛选了它们对四种肿瘤细胞系（Hela、HepG-2、BGC-823 和 SK-SY5Y）的体外细胞毒性。大多数这些衍生物显示出比 BA 强得多的细胞毒活性。值得注意的是，最有效的化合物 7e（其半数抑制浓度 (IC50) 为 2.05 ± 0.66 μM）的体外毒性是 BA 处理的 Hela 的 12 倍。此外，多种荧光染色技术和流式细胞术共同揭示了化合物7e可以诱导Hela细胞的早期凋亡。还简要讨论了构效关系。本研究强调了将氮杂环引入桦木酸在新型抗肿瘤药物的发现和开发中的重要性。

  DOI：

  10.3390/molecules25040948

文献信息

• Polyamine derivatives of betulinic acid and β-sitosterol: A comparative investigation
  作者：Uladzimir Bildziukevich、Norbert Vida、Lucie Rárová、Milan Kolář、David Šaman、Libor Havlíček、Pavel Drašar、Zdeněk Wimmer

  DOI：10.1016/j.steroids.2015.04.005

  日期：2015.8

  beta-Sitosterol and betulinic acid were used in designing their conjugates with selected polyamines bearing either an amide bond, or an ester and an amide bond simultaneously in the target molecule. The synthesized compounds were subjected to basic cytotoxic and antimicrobial tests. The synthetic protocol is described separately for each of the three series of the target amides, because each series of compounds required a different synthetic approach. The cytotoxicity was tested on cells derived from human T-lymphoblastic leukemia, breast adenocarcinoma and cervical cancer, and compared with the tests on normal human fibroblasts. Most of the target compounds (5a-5c, 11a-11c and 16a-16c) showed medium to high cytotoxicity (0.7-7.8 mu M), however, in some cases the compounds showed high cytotoxicity even toward normal human fibroblasts (11a-11c). Two compounds of this series (11c and 16c) also displayed antimicrobial activity with high and selective microbe specificity. The compound 11c was potent against Escherichia coli (minimal inhibition concentration (MIC) 6.25 mu g mL(-1), i.e. 9.75 nM mL(-1)) and Staphylococcus aureus (MIC 12.5 mu g mL(-1), i.e. 19.5 nM mL(-1)), and showed medium activity against Pseudomonas aeruginosa. The compound 16c was highly active against Enterococcus faecalis and S. aureus (both, MIC 3.125 mu g mL(-1), i.e. 4.22 nM mL(-1)), both Gram-positive bacteria, however showed only weak activity against E. coli and no activity against P. aeruginosa, both Gram-negative bacteria, which indicates possible microbe specificity of 16c. Comparing beta-sitosterol-based series (5a-5c) and betulinic acid series (11a-11c and 16a-16c) of the target compounds, the latter one gave more promising structures. The compounds 11c and 16c showed effects which may be described as multifarious activity (pleiotropic effects). (C) 2015 Elsevier Inc. All rights reserved.
• Spectral and microscopic study of self-assembly of novel cationic spermine amides of betulinic acid
  作者：Uladzimir Bildziukevich、Eva Kaletová、David Šaman、Elina Sievänen、Erkki T. Kolehmainen、Miroslav Šlouf、Zdeněk Wimmer

  DOI：10.1016/j.steroids.2016.07.007

  日期：2017.1

  Supramolecular characteristics of two spermine amides of betulinic acid (1 and 2) were studied by measuring and evaluating their UV-VIS-NIR spectra in aqueous acetonitrile and DOSY-NMR spectra in tetra-deuteromethanol, accompanied by atomic force microscopy (AFM) images, scanning electron microscopy (SEM) micrographs, and transmission electron microscopy (TEM) micrographs. Fibrous supramolecular self-assembly of 1 and 2 was observed by AFM images, as well as by the SEM and TEM micrographs. Bathochromic shifts of the absorbance maximum at 870 nm to 1015-970 nm in the UV-VIS-NIR spectra were observed with increasing water content in the acetonitrile/water systems, indicating formation of fibrous J-type aggregates. Variable temperature DOSY-NMR spectral measurement showed non-linear dependence that also suggests self-assembly behavior of the studied systems. Chiral supramolecular structures were formed by self-assembling due to the chirality of the monomeric molecules. Application of aqueous media during self-assembly procedures is an important factor in the development of targeted drug delivery systems. (C) 2016 Elsevier Inc. All rights reserved.
• Antimicrobial properties of amine- and guanidine-functionalized derivatives of betulinic, ursolic and oleanolic acids: Synthesis and structure/activity evaluation
  作者：Anna Yu. Spivak、Rezeda R. Khalitova、Darya A. Nedopekina、Rinat R. Gubaidullin

  DOI：10.1016/j.steroids.2019.108530

  日期：2020.2

  A series of 34 new amine- and guanidine-functionalized derivatives of betulinic, ursolic, and oleanolic acids were synthesized and tested for their antimicrobial activity against the growth of four bacterial strains (Escherichia colt Acinetobacter baumannii, Pseudomonas aeruginosa, and Staphylococcus aureus (MESA)) and two fungal strains (Candida albicans and Cryptococcus neoformans). The obtained compounds were also tested for the cytotoxic effect against HEK293 human embryonic kidney cell line and hemolytic activity against human red blood cells. Most of the prepared amino and guanidinium derivatives of betulinic, ursolic, and oleanolic acids showed a considerably higher bacteriostatic activity against methicillin-resistant S. aureus than the parent compounds. The most active compounds (MICs <= 0.25 mu g/ml or 0.4-0.5 mu M) were superior over the clinically used antibiotic vancomycin in the antibacterial effect (MIC of 1 mu g/ml or 0.7 mu M). Apart from antibacterial activity, new triterpene acid derivatives exhibited excellent antifungal activity against Cryptococcus neoformans, with MICs values being as low as 0.25 mu g/ml (0.4 mu M), and were approximately 65 times as active as fluconazole, a known antifungal agent. Four most promising compounds we identified (7, 13, 24, and 33) showed not only high bacteriostatic effect, but also low cytotoxicity against mammalian HEK293 cells and high hemolytic selectivity.