(2R,3S)-1-(tert-butyldiphenylsilyloxy)-2,3-isopropylidenedioxyhex-5-ene | 1251854-62-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2R,3S)-1-(tert-butyldiphenylsilyloxy)-2,3-isopropylidenedioxyhex-5-ene
• 英文别名: tert-butyl-[[(4R,5S)-2,2-dimethyl-5-prop-2-enyl-1,3-dioxolan-4-yl]methoxy]-diphenylsilane
• CAS: 1251854-62-2
• 化学式: C₂₅H₃₄O₃Si
• 分子量: 410.629
• InChiKey: SNMCRTAPDPBRSD-XZOQPEGZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.66
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  27.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2R,3S)-1-(tert-butyldiphenylsilyloxy)-2,3-isopropylidenedioxyhex-5-ene 在 sodium chlorite 、 potassium phosphate 、 sodium dihydrogenphosphate 、 2-甲基-2-丁烯 、 四丁基氟化铵 、 碳酸氢钠 、 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 叔丁醇 为溶剂， 反应 8.0h， 生成
  参考文献：
  名称：

  Identification of the First Selective Activin Receptor-Like Kinase 1 Inhibitor, a Reversible Version of L-783277

  摘要：

  We synthesized 1 (San78-130), a reversible version of L-783277, as a selective and potent ALK1 inhibitor. Our study showed that 1 possesses great kinase selectivity against a panel of 342 kinases and more potent activity against ALK1 than L-783277. Among the six ALK isotypes (ALK1-6), ALK1 is most significantly inhibited by compound 1. Compound 1 suppresses the BMP9-induced Smad1/5 pathway by mainly inhibiting ALK1 in C2C12 cells. Our molecular dynamics simulations suggest that H-bonding interaction between the C-4' hydroxyl group of 1 and Arg334 of ALK1 substantially contributes to the ALK1 inhibition. To the best of our knowledge, 1 is the first selective ALK1 inhibitor. Furthermore, compound 1 promoted angiogenesis in both endothelial tube formation and microfluidic chip based 3D angiogenesis assays, suggesting that 1 could be a lead compound for therapeutic angiogenesis agents. Our study may provide an insight into designing selective and potent inhibitors against ALK1.

  DOI：

  10.1021/acs.jmedchem.6b01679
• 作为产物：
  描述：

  1(S)-[(2R)-1,4-dioxaspiro[4.5]decanyl]-3-buten-1-ol 在 盐酸 、 4-甲基苯磺酸吡啶 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 mineral oil 为溶剂， 反应 28.33h， 生成 (2R,3S)-1-(tert-butyldiphenylsilyloxy)-2,3-isopropylidenedioxyhex-5-ene
  参考文献：
  名称：

  Acortatarin A 修正结构的合成

  摘要：

  衍生自 D-甘露醇的伯胺与二氢吡喃酮之间的新型美拉德型缩合被用作获得不寻常的吗啉-螺旋酮醇 Acortatarin A 的关键步骤。该合成方法还能够获得 acortatarin A 的 C-2 类似物，可用于合成相关的2-甲酰基吡咯天然产物。

  DOI：

  10.1002/ejoc.201403000

文献信息

• An efficient and enantioselective total synthesis of naturally occurring L-783277
  作者：Hwan Geun Choi、Jung Beom Son、Dong-Sik Park、Young Jin Ham、Jung-Mi Hah、Taebo Sim

  DOI：10.1016/j.tetlet.2010.07.122

  日期：2010.9

  Naturally occurring L-783277 which belongs to 14-membered resorcylic acid lactones (RALs) turned out to be a potent kinase inhibitor against MEK (MAP kinase kinase). We successfully accomplished efficient and enantioselective total synthesis of L-783277 based on convergent assembly of one aromatic unit and two chiral building blocks with efficient orthogonal protection-deprotection strategy. Three

  属于14元间苯二酸内酯（RAL）的天然存在的L-783277被证明是一种有效的针对MEK的激酶抑制剂（MAP激酶激酶）。我们成功地完成了L-783277的高效和对映选择性合成，这是基于一个芳香单元和两个手性结构单元的聚合组装以及有效的正交保护-去保护策略而完成的。随后采用三个关键步骤组成烯烃交叉复分解，向乙醛中添加乙炔衍生物和山口大内酯化来构建L-783277的构架。L-783277的旋光度值是本函中的首次。
• A Convergent Synthesis of the 2-Formylpyrrole Spiroketal Natural Product Acortatarin A
  作者：Margaret Brimble、Hui Geng、Jack Chen、Daniel Furkert、Shende Jiang

  DOI：10.1055/s-0031-1290508

  日期：2012.4

  flexible synthesis of the morpholine-spiroketal natural product acortatarin A, isolated from the traditional Chinese medicine Acorus tatarinowii, is reported. The key step involves a Maillard-type condensation of an amine derived from d -mannitol with a dihydropyranone. The approach also enables access to analogues of acortatarin A for biological evaluation and can be applied to the synthesis of related

  报道了从中药蒺藜中分离的吗啉-螺酮天然产物 acortatarin A 的简洁灵活的合成方法。关键步骤涉及衍生自 d-甘露醇的胺与二氢吡喃酮的美拉德型缩合。该方法还能够获得用于生物学评价的 acortatarin A 类似物，并可应用于相关 2-甲酰基吡咯天然产物的合成。
• Total Synthesis of Spiroketal Alkaloids Lycibarbarines A–C
  作者：Eilidh G. Young、Phillip S. Grant、Daniel P. Furkert、Margaret A. Brimble

  DOI：10.1021/acs.orglett.3c00902

  日期：2023.4.28

  Lycibarbarines A–C are spirocyclic alkaloids with a unique tetracyclic framework, consisting of tetrahydroquinoline and spiro-fused oxazine–sugar spiroketal subunits. The first total syntheses of lycibarbarines A–C were achieved over 10 steps (longest linear sequence) each. Through this work, it was discovered that the spiroketal unit of lycibarbarines A–C exhibits unusually high resistance to acid-mediated

  Lycibarbarines A–C 是具有独特四环框架的螺环生物碱，由四氢喹啉和螺稠恶嗪-糖螺缩酮亚基组成。lycibarbarines A–C 的第一次全合成是通过 10 个步骤（最长的线性序列）实现的。通过这项工作，人们发现 lycibarbarines A–C 的螺缩酮单元对酸介导的异构化和差向异构化表现出异常高的抵抗力，这可能是由于碱性氮原子。因此，lycibarbarines 在防止螺缩酮异构体相互转化方面提供了一个有趣的案例研究，这可能对获得非热力学螺缩酮框架的努力具有指导意义。
• Synthesis of the Revised Structure of Acortatarin A
  作者：Hui Min Geng、Louise A. Stubbing、Jack Li-yang Chen、Daniel P. Furkert、Margaret A. Brimble

  DOI：10.1002/ejoc.201403000

  日期：2014.10

  dihydropyranone, was used as a key step to access the unusual morpholine-spiroketal acortatarin A. The synthetic approach also enabled access to a C-2 analogue of acortatarin A, and can be used for the synthesis of related 2-formylpyrrole natural products.

  衍生自 D-甘露醇的伯胺与二氢吡喃酮之间的新型美拉德型缩合被用作获得不寻常的吗啉-螺旋酮醇 Acortatarin A 的关键步骤。该合成方法还能够获得 acortatarin A 的 C-2 类似物，可用于合成相关的2-甲酰基吡咯天然产物。
• Identification of the First Selective Activin Receptor-Like Kinase 1 Inhibitor, a Reversible Version of L-783277
  作者：Hanna Cho、Sandip Sengupta、Sean S. H. Jeon、Wooyoung Hur、Hwan Geun Choi、Hong-Seog Seo、Byung Joo Lee、Jeong Hun Kim、Minhwan Chung、Noo Li Jeon、Nam Doo Kim、Taebo Sim

  DOI：10.1021/acs.jmedchem.6b01679

  日期：2017.2.23

  We synthesized 1 (San78-130), a reversible version of L-783277, as a selective and potent ALK1 inhibitor. Our study showed that 1 possesses great kinase selectivity against a panel of 342 kinases and more potent activity against ALK1 than L-783277. Among the six ALK isotypes (ALK1-6), ALK1 is most significantly inhibited by compound 1. Compound 1 suppresses the BMP9-induced Smad1/5 pathway by mainly inhibiting ALK1 in C2C12 cells. Our molecular dynamics simulations suggest that H-bonding interaction between the C-4' hydroxyl group of 1 and Arg334 of ALK1 substantially contributes to the ALK1 inhibition. To the best of our knowledge, 1 is the first selective ALK1 inhibitor. Furthermore, compound 1 promoted angiogenesis in both endothelial tube formation and microfluidic chip based 3D angiogenesis assays, suggesting that 1 could be a lead compound for therapeutic angiogenesis agents. Our study may provide an insight into designing selective and potent inhibitors against ALK1.