| 225116-32-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• CAS: 225116-32-5
• 化学式: C₁₈H₃₈OSn
• 分子量: 389.209
• InChiKey: BYOQADUYNWVKFF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.36
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  、 (3S,8E,11S)-3-[(E)-2-bromoprop-1-enyl]-9,11-dimethyl-4,12-dioxa-20-thia-21-azabicyclo[16.2.1]henicosa-1(21),8,18-trien-6-yne-5,13-dione 在 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以38%的产率得到
  参考文献：
  名称：

  Second-generation derivatives of the eukaryotic translation initiation inhibitor pateamine A targeting eIF4A as potential anticancer agents

  摘要：

  A series of pateamine A (1) derivatives were synthesized for structure/activity relationship (SAR) studies and a selection of previous generation analogs were re-evaluated based on current information regarding the mechanism of action of these translation inhibitors. Structural modifications in the new generation of derivatives focused on alterations to the C19-C22 Z,E-diene and the trienyl side chain of the previously described simplified, des-methyl, des-amino pateamine A (DMDAPatA, 2). Derivatives were tested for anti-proliferative activity in cell culture and for inhibition of mammalian cap-dependent translation in vitro. Activity was highly dependent on the rigidity and conformation of the macrolide and the functionality of the side chain. The only well tolerated substitutions were replacement of the N,N-dimethyl amino group found on the side chain of 2 with other tertiary amine groups. SAR reported here suggests that this site may be modified in future studies to improve serum stability, cell-type specificity, and/or specificity towards rapidly proliferating cells. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.11.046
• 作为产物：
  描述：

  (E)-5-(tributylstannyl)pent-4-en-1-ol 、 碘甲烷 在 silver(l) oxide 作用下， 以 乙腈 为溶剂， 以25%的产率得到
  参考文献：
  名称：

  免疫抑制和抗肿瘤天然产物 Pateamine A 中单独结合和支架结构域的证据：设计、合成和活性研究导致有效的简化衍生物

  摘要：

  Pateamine A (PatA) 是一种来自 Mycale sp. 的海洋代谢物，是 T 细胞受体发出的细胞内信号转导途径的有效抑制剂，可导致细胞因子如白细胞介素 2 (IL-2) 的转录。基于 PatA 的结构和最初的生物学结果，提出了一个假设，即 PatA 结构中存在不同的结合和支架结构域，与它推定的细胞受体的相互作用有关。我们采用涉及 Hantzsch 耦合策略的高度收敛方法，通过制备简化的 PatA 衍生物（去甲基、去氨基 PatA、DMDAPatA、3）来探讨这一假设。与 PatA 相比，该衍生物的合成步骤少了 10 步，并且确实发现其具有更高的效力（IC50 0.81 +/- 0 27 nM) 相对于 PatA (IC50 4.01 +/- 0.94 nM) 抑制 IL-2 产生，从而为结合/支架结构域假设提供支持。此外，为了找到更稳定的衍生物并进一步了解构效关系，在 IL-2

  DOI：

  10.1021/ja040065s

文献信息

• Evidence for Separate Binding and Scaffolding Domains in the Immunosuppressive and Antitumor Marine Natural Product, Pateamine A:  Design, Synthesis, and Activity Studies Leading to a Potent Simplified Derivative
  作者：Daniel Romo、Nam Song Choi、Shukun Li、Ingrid Buchler、Zonggao Shi、Jun O. Liu

  DOI：10.1021/ja040065s

  日期：2004.9.1

  Pateamine A (PatA), a marine metabolite from Mycale sp., is a potent inhibitor of the intracellular signal transduction pathway emanating from the T-cell receptor leading to the transcription of cytokines such as interleukin-2 (IL-2). On the basis of the structure of PatA and initial biological results, a hypothesis was developed regarding the presence of distinct binding and scaffolding domains in

  Pateamine A (PatA) 是一种来自 Mycale sp. 的海洋代谢物，是 T 细胞受体发出的细胞内信号转导途径的有效抑制剂，可导致细胞因子如白细胞介素 2 (IL-2) 的转录。基于 PatA 的结构和最初的生物学结果，提出了一个假设，即 PatA 结构中存在不同的结合和支架结构域，与它推定的细胞受体的相互作用有关。我们采用涉及 Hantzsch 耦合策略的高度收敛方法，通过制备简化的 PatA 衍生物（去甲基、去氨基 PatA、DMDAPatA、3）来探讨这一假设。与 PatA 相比，该衍生物的合成步骤少了 10 步，并且确实发现其具有更高的效力（IC50 0.81 +/- 0 27 nM) 相对于 PatA (IC50 4.01 +/- 0.94 nM) 抑制 IL-2 产生，从而为结合/支架结构域假设提供支持。此外，为了找到更稳定的衍生物并进一步了解构效关系，在 IL-2
• Second-generation derivatives of the eukaryotic translation initiation inhibitor pateamine A targeting eIF4A as potential anticancer agents
  作者：Woon-Kai Low、Jing Li、Mingzhao Zhu、Sai Shilpa Kommaraju、Janki Shah-Mittal、Ken Hull、Jun O. Liu、Daniel Romo

  DOI：10.1016/j.bmc.2013.11.046

  日期：2014.1

  A series of pateamine A (1) derivatives were synthesized for structure/activity relationship (SAR) studies and a selection of previous generation analogs were re-evaluated based on current information regarding the mechanism of action of these translation inhibitors. Structural modifications in the new generation of derivatives focused on alterations to the C19-C22 Z,E-diene and the trienyl side chain of the previously described simplified, des-methyl, des-amino pateamine A (DMDAPatA, 2). Derivatives were tested for anti-proliferative activity in cell culture and for inhibition of mammalian cap-dependent translation in vitro. Activity was highly dependent on the rigidity and conformation of the macrolide and the functionality of the side chain. The only well tolerated substitutions were replacement of the N,N-dimethyl amino group found on the side chain of 2 with other tertiary amine groups. SAR reported here suggests that this site may be modified in future studies to improve serum stability, cell-type specificity, and/or specificity towards rapidly proliferating cells. (C) 2013 Elsevier Ltd. All rights reserved.