brefeldin A 4,7-O-diacetate | 29129-37-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: brefeldin A 4,7-O-diacetate
• 英文别名: brefeldin A-1,13-diacetate；brefeldin A diacetate；diacetyl brefeldin A；BFA；Decumbin-diacetat；[(1R,2R,3E,7S,11E,13S,15S)-2-acetyloxy-7-methyl-5-oxo-6-oxabicyclo[11.3.0]hexadeca-3,11-dien-15-yl] acetate
• CAS: 29129-37-1
• 化学式: C₂₀H₂₈O₆
• 分子量: 364.439
• InChiKey: ILLPGJFSCLASDH-SVJSBHBHSA-N

物化性质

• 熔点：
  122 °C
• 沸点：
  493.7±45.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  78.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  brefeldin A 4,7-O-diacetate 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 生成 布雷非德菌素 A
  参考文献：
  名称：

  Gais, Hans-Joachim; Lied, Thomas, Angewandte Chemie, 1984, vol. 96, # 2, p. 143 - 145

  摘要：

  DOI：
• 作为产物：
  描述：

  布雷非德菌素 A 在 azodicarbonic acid ethylester 、 potassium carbonate 、 三苯基膦 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 为溶剂， 生成 brefeldin A 4,7-O-diacetate
  参考文献：
  名称：

  Gais, Hans-Joachim; Lied, Thomas, Angewandte Chemie, 1984, vol. 96, # 2, p. 143 - 145

  摘要：

  DOI：

文献信息

• Site-specific allylic C–H bond functionalization with a copper-bound N-centred radical
  作者：Jiayuan Li、Zhihan Zhang、Lianqian Wu、Wen Zhang、Pinhong Chen、Zhenyang Lin、Guosheng Liu

  DOI：10.1038/s41586-019-1655-8

  日期：2019.10.24

  sp 3 C–H bonds with comparable properties. If the intermediate radical could be further trapped enantioselectively, this should enable highly site- and enantioselective functionalization of C–H bonds. Here we report a copper (Cu)-catalysed site- and enantioselective allylic C–H cyanation of complex alkenes, in which a Cu(ii)-bound nitrogen (N)-centred radical plays the key role in achieving precise site-specific

  选择性 C-H 键功能化的方法为化学家提供了多功能且强大的合成工具箱，例如先导化合物的后期修饰，而无需冗长的从头合成 1-5。考虑到大量可用的 HAT 受体和生成的自由基中间体 6-17 可用的反应途径的多样性，通过氢原子转移 (HAT) 裂解 sp 3 C-H 键特别有用。然而，位点选择性仍然是一个巨大的挑战，尤其是在具有可比性质的 sp 3 C-H 键中。如果中间自由基可以进一步被对映选择性捕获，这应该能够实现 C-H 键的高度位点和对映选择性功能化。在这里，我们报告了复杂烯烃的铜 (Cu) 催化位点和对映选择性烯丙基 C-H 氰化，其中以 Cu(ii) 结合的氮 (N) 为中心的自由基在实现精确的位点特异性 HAT 中起着关键作用。这种方法被证明对各种含烯烃分子的集合有效，包括空间要求高的结构和复杂的天然产物和药物。Cu结合的以氮为中心的自由基用于控制具有合成和医学相关性的分子（例如
• Synthesis and Anticancer Activity of Brefeldin A Ester Derivatives
  作者：Nwanne O. Anadu、V. Jo Davisson、Mark Cushman

  DOI：10.1021/jm0602817

  日期：2006.6.1

  Ester derivatives of brefeldin A ( BFA) were synthesized to determine which of its two hydroxyl groups could be modified while still maintaining biological activity. The compounds were tested for antiproliferative activity in the National Cancer Institute's 60 cancer cell line screen. Monoderivatization at the C4 and C7 alcohols was tolerated, yielding biologically active compounds, whereas the analogues derivatized at both positions were the least active in the series. Molecular modeling of the analogues revealed that both the C4 and C7 derivatives were well tolerated at the interface between ARF1 and its guanine nucleotide exchange factor ARNO. The Golgi-disruptive properties of the analogues were determined using fluorescence imaging assays. The BFA ester conjugates synthesized in this study were cytotoxic to cancer cells, and we have shown that the disruption of the Golgi complex is not necessary for cytotoxicity. The brefeldin A ester derivatives are potential anticancer agents.
• Elucidation of strict structural requirements of Brefeldin A as an inducer of differentiation and apoptosis
  作者：Ji-Wen Zhu、Hideko Nagasawa、Fumi Nagura、Saharuddin B Mohamad、Yoshihiro Uto、Kazuto Ohkura、Hitoshi Hori

  DOI：10.1016/s0968-0896(99)00297-7

  日期：2000.2

  Brefeldin A (BFA) can induce a wide variety of human cancer cells to differentiation and apoptosis and is in development as an anticancer agent. To elucidate structural requirements for cytotoxicity and induction of differentiation and apoptosis, BFA was structurally modified into various derivatives including 4-epi-BFA in this study. Their inducing activities of apoptosis were evaluated with their cytotoxicities, DNA fragmentation and morphological changes in human colon cancer cell HCT 116. The cytotoxicity of 4-epi-BFA (TX-1923) (IC50 = 60 mu M) was 300 times lower than that of BFA (IC50 = 0.2 mu M). Furthermore, 4-epi-BFA induced DNA fragmentation and apoptotic morphological changes at much higher concentrations (70 and 50 mu M, respectively) than BFA (0.11 and 0.36 mu M, respectively). These results indicated that the configuration of 4-hydroxyl group of brefeldin A plays a key role in the cytotoxicity and induction of apoptosis. On the other hand, 7-O-acetyl-BFA, 4-O-acetyl-BFA, and 4,7-di-O-acetyl-BFA exhibited potential activities in cytotoxicity and inducibility of apoptosis. We suggested that the structural determinants for BFA include the moiety of the Michael acceptor, the conformational rigidity of the 13-membered ring, and the configuration of 4-hydroxyl group. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Synthesis and Cytotoxic Evaluation of Acylated Brefeldin A Derivatives as Potential Anticancer Agents
  作者：Bingyong He、Yajun Wang、Yuguo Zheng、Wei Chen、Qing Zhu

  DOI：10.1111/cbdd.12154

  日期：2013.9

  Brefeldin A has attracted considerable attention because of its potential function in cancer prevention. However, its therapeutic use is limited by its poor bioavailability. The modifications on brefeldin A were difficult because of its low stability and selectivity toward two hydroxyl groups within the same molecule. In this study, we report the selective acylation of brefeldin A under mild conditions and the preparation of a series of monoacylated and diacylated brefeldin A derivatives. Their cytotoxicity, antitumor activity against TE‐1 cell, and molecular properties of adsorption, distribution, metabolism, and elimination were evaluated. Brefeldin A 7‐O‐benzoate, brefeldin A 4,7‐O‐dibenzoate, and brefeldin A 7‐O‐biotin carboxylate showed the most potent cytotoxic activity, with GI50 values of 0.39, 0.46, and 0.50 μm, respectively. Molecular docking of these analogs revealed that the derivatives were well tolerated at the interface between ARF1 and its guanine nucleotide exchange factor ARNO. Our results may serve as a basis for the development of novel potential anticancer agents from brefeldin A derivatives.
• Synthesis and activity of brefeldin a analogs as inducers of cancer cell differentiation and apoptosis
  作者：Ji-Wen Zhu、Hitoshi Hori、Hisao Nojiri、Takahiko Tsukuda、Zenei Taira

  DOI：10.1016/s0960-894x(96)00588-4

  日期：1997.1

  We designed and synthesized several brefeldin A (BFA) analogs. These compounds were evaluated for the ability to induce differentiation and apoptosis in human colonic carcinoma cell line HCT116. Diacetyl BFA (2a), 4-acetyl BFA (2b), 7-acetyl BFA (2c), and 10,11-epoxy BFA (3b) were active but tetrahydro BFA (3a) and other analogs could not induce the malignant cells to differentiate. The results suggested that the moiety from 1- to 4-position in BFA as well as its conformational rigidity is essential for its biological activity. (C) 1997, Elsevier Science Ltd.