(+)-epibrefeldin A | 267667-13-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: (+)-epibrefeldin A
• 英文别名: 4-epi-brefeldin A；4-epibrefeldin A；(+)-brefeldin A；(+)-brefeldin；(1S,2E,7S,10E,12S,13R,15S)-12,15-dihydroxy-7-methyl-8-oxabicyclo[11.3.0]hexadeca-2,10-dien-9-one；(1R,2S,3E,7S,11E,13S,15S)-2,15-dihydroxy-7-methyl-6-oxabicyclo[11.3.0]hexadeca-3,11-dien-5-one
• CAS: 267667-13-0
• 化学式: C₁₆H₂₄O₄
• 分子量: 280.364
• InChiKey: KQNZDYYTLMIZCT-PNFJWZTBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+)-epibrefeldin A 在 4 A molecular sieve 重铬酸吡啶 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 生成 (2E,6S,10E,11aS,13S,14aR,)-7,8,9,11a,12,13,14,14a-octahydro-13-(2-methoxyethoxymethoxy)-6-methyl-6H-cyclopent--oxacyclotridecin-1,4-dione
  参考文献：
  名称：

  （+）-布雷菲德菌素A的全合成

  摘要：

  （+）-布雷菲德菌素A的总合成已通过15个线性步骤完成，从已知的Weinreb酰胺6获得了7.9％的总收率。该方法的关键部分包括立体选择性构建的顺式二取代羟基环戊烷骨架和直接使用反式乙烯基阴离子同等物的新变体引入C1-C3丙烯酸酯部分。

  DOI：

  10.1021/jo0110855
• 作为产物：
  描述：

  布雷非德菌素 A 在 manganese(IV) oxide 、 L-Selectride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.5h， 生成 (+)-epibrefeldin A
  参考文献：
  名称：

  Elucidation of strict structural requirements of Brefeldin A as an inducer of differentiation and apoptosis

  摘要：

  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.

  DOI：

  10.1016/s0968-0896(99)00297-7

文献信息

• Facile synthesis of (+)-brefeldin A
  作者：Junzo Nokami、Mamoru Ohkura、Yasufumi Dan-Oh、Yasuhiko Sakamoto

  DOI：10.1016/s0040-4039(00)79936-9

  日期：1991.5

  (+)-Brefeldin A (1) was synthesized by using (+)-4-cyanomethylcyclopent-2-ene-1-one (2) as a key compound. 4-Hydroxy-2-enoate functionality was built by the reaction of the aldehyde (7) with (S)-ethyl p-chlorophenylsulfinylacetate.

  (+)-Brefeldin A (1) 通过使用 (+)-4-氰甲基环戊-2-烯-1-酮 (2) 作为关键化合物进行了合成。4-羟基-2-烯酸酯基团由醛 (7) 与 (S)-乙基-p-氯苯亚砜乙酸酯的反应构建而成。
• Total Synthesis of the Antitumor Macrolides, (+)-Brefeldin A and 4-Epi-Brefeldin A from <scp>d</scp>-Glucose: Use of the Padwa Anionic Allenylsulfone [3 + 2]-Cycloadditive Elimination To Construct Trans-Configured Chiral Cyclopentane Systems
  作者：Ziyue Xiong、Karl J. Hale

  DOI：10.1021/acs.orglett.6b02002

  日期：2016.9.2

  A new synthesis of (+)-brefeldin A is reported via Padwa allenylsulfone [3 + 2]-cycloadditive elimination. Cycloadduct 13 was initially elaborated into iodide 27, which, following treatment with Zn, gave aldehyde 28 whose C(9) stereocenter was epimerized. Further elaboration into enoate 38 and Julia–Kocienski olefination with 5 subsequently afforded 39, which was deprotected at C(1) and O(15). Yamaguchi

  通过Padwa烯基砜[3 + 2]-环加成消除法报道了一种新的（+）-布雷菲德菌素A合成方法。首先将环加合物13精制为碘化物27，用Zn处理后，得到醛28，其C（9）立体中心被差向异构化。进一步加工成烯酸酯38和Julia-Kocienski与5的烯烃，随后得到39，在C（1）和O（15）脱保护。所述的山口macrolactonization开环-酸之后，得到大环化合物将经历O型脱甲硅基和反演在C（4），得到（+） -后的脱保护布雷菲德菌素A。
• Concise Total Synthesis of (+)-Brefeldin A:  A Combined β-Lactone/Cross-Metathesis-Based Strategy
  作者：Yingcai Wang、Daniel Romo

  DOI：10.1021/ol026438g

  日期：2002.9.1

  A highly convergent total synthesis of (+)-brefeldin A that relies on a diastereoselective, beta-lactone-based cyclopentane synthesis combined with complex cross-metathesis reactions is described. The utility of beta-lactones for natural product synthesis and the versatility of cross-metathesis in this context were demonstrated, including the tolerance of an epimerizable aldehyde and a beta-lactone.
• HATAKEYAMA, S.;SUGAWARA, K.;KAWAMURA, M., SYNLETT.,(1990) N1, C. 691-693
  作者：HATAKEYAMA, S.、SUGAWARA, K.、KAWAMURA, M.

  DOI：——

  日期：——
• ACKER, R. -D.;KARL, R.;WUERZER, B.
  作者：ACKER, R. -D.、KARL, R.、WUERZER, B.

  DOI：——

  日期：——