[(2S)-3-[(2R,3R,4S,5S)-4-(benzenesulfonylmethyl)-5-[[(2R,4R,6S)-6-(3-hydroxypropyl)-4-methyl-3-methylideneoxan-2-yl]methyl]-3-methoxyoxolan-2-yl]-2-benzoyloxypropyl] benzoate | 1193375-00-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [(2S)-3-[(2R,3R,4S,5S)-4-(benzenesulfonylmethyl)-5-[[(2R,4R,6S)-6-(3-hydroxypropyl)-4-methyl-3-methylideneoxan-2-yl]methyl]-3-methoxyoxolan-2-yl]-2-benzoyloxypropyl] benzoate
• CAS: 1193375-00-6
• 化学式: C₄₀H₄₈O₁₀S
• 分子量: 720.881
• InChiKey: SUXZQHPUMIWZBD-QYUFXNHBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  51
• 可旋转键数：
  18
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  143
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  [(2S)-3-[(2R,3R,4S,5S)-4-(benzenesulfonylmethyl)-5-[[(2R,4R,6S)-6-(3-hydroxypropyl)-4-methyl-3-methylideneoxan-2-yl]methyl]-3-methoxyoxolan-2-yl]-2-benzoyloxypropyl] benzoate 在 碳酸氢钠 、 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以96%的产率得到[(2S)-3-[(2R,3R,4S,5S)-4-(benzenesulfonylmethyl)-3-methoxy-5-[[(2R,4R,6S)-4-methyl-3-methylidene-6-(3-oxopropyl)oxan-2-yl]methyl]oxolan-2-yl]-2-benzoyloxypropyl] benzoate
  参考文献：
  名称：

  E7389 C14-C35 和软海绵素 C14-C38 构件的新合成：还原环化和氧-迈克尔环化方法

  摘要：

  Cr 介导的偶联反应通常在给定亲核试剂略微过量的情况下实现。为了开发该过程的经济有效的使用，已经研究了两种不同的方法。第一种方法依赖于两个连续的催化不对称 Cr 介导的偶联，偶联伙伴的使用有意使分子大小和复杂性不平衡。第二种方法依赖于确定亲核试剂的成功，这使我们能够以 1:1 的偶联伙伴摩尔比令人满意地实现偶联。C23-O 键是通过氧鎓离子的还原环化或氧-迈克尔环化立体有择地构建的。两种合成都具有较高的整体效率：E7389 C14-C35 和软海绵素 C14-C38 构建块已由相应的 C27-C35 和 C27-C38 醛合成，分别以高总产率和优异的立体选择性。由于操作简单，本文概述的合成似乎非常适合缩放。

  DOI：

  10.1021/ja9058487
• 作为产物：
  描述：

  C₅₉H₇₂O₁₂SSi 在 三乙基硅烷 、 三氟甲磺酸三甲基硅酯 作用下， 以 二氯甲烷 为溶剂， 反应 2.08h， 以95%的产率得到[(2S)-3-[(2R,3R,4S,5S)-4-(benzenesulfonylmethyl)-5-[[(2R,4R,6S)-6-(3-hydroxypropyl)-4-methyl-3-methylideneoxan-2-yl]methyl]-3-methoxyoxolan-2-yl]-2-benzoyloxypropyl] benzoate
  参考文献：
  名称：

  Dramatic Improvement in Catalyst Loadings and Molar Ratios of Coupling Partners for Ni/Cr-Mediated Coupling Reactions: Heterobimetallic Catalysts

  摘要：

  Two new ligands 1a,b are reported. Upon treatment with 1 equiv of NiCl2 center dot(MeOCH2)(2), 1a,b give the corresponding Ni complexes. X-ray analysis of 1a-NiCl2 established that the NiCl2 is selectively coordinated to the phenanthroline nitrogens. Ni/Cr heterobimetallic catalysts 1a,b center dot CrCl2/NiCl2, prepared from 1a,b center dot NiCl2, have been shown to behave exceptionally well in catalytic asymmetric Ni/Cr-mediated couplings, with highlights including the following: (1) 1-2 mol % catalyst is sufficient to complete the coupling; (2) only negligible amounts of the dimers, byproducts formed through the alkenyl Ni species, are observed; (3) the coupling goes to completion even with a 1:1 molar ratio of the coupling partners; and (4) the asymmetric induction is practically identical with that obtained from the coupling with the Cr catalysts prepared from (S)-sulfonamides 2a,b. The scope of the new Ni/Cr heterobimetallic catalysts was briefly studied using four additional aldehydes. The applicability of the new catalysts to polyfunctional substrates was demonstrated by two C-C bond formations chosen from the hatichondrin/E7389 synthesis as examples.

  DOI：

  10.1021/ja9079308

文献信息

• MACROCYCLIZATION REACTIONS AND INTERMEDIATES USEFUL IN THE SYNTHESIS OF ANALOGS OF HALICHONDRIN B
  申请人：FANG Francis G.

  公开号：US20160264594A1

  公开（公告）日：2016-09-15

  The invention provides methods for the synthesis of eribulin or a pharmaceutically acceptable salt thereof (e.g., eribulin mesylate) through a macrocyclization strategy. The macrocyclization strategy of the present invention involves subjecting a non-macrocyclic intermediate to a carbon-carbon bond-forming reaction (e.g., an olefination reaction (e.g., Homer-Wadsworth-Emmons olefination), Dieckmann reaction, catalytic Ring-Closing Olefin Metathesis, or Nozaki-Hiyama-Kishi reaction) to afford a macrocyclic intermediate. The invention also provides compounds useful as intermediates in the synthesis of eribulin or a pharmaceutically acceptable salt thereof and methods for preparing the same.

  本发明提供了通过大环化策略合成厄利布林或其药学上可接受的盐（例如，甲磺酸厄利布林）的方法。本发明的大环化策略涉及将非大环中间体经过碳-碳键形成反应（例如，烯化反应（例如，霍默-沃兹沃斯-埃蒙斯烯化反应），迪克曼反应，催化环内烯烃交换反应，或野崎-桥山-岸反应）处理，以得到大环中间体。本发明还提供了在合成厄利布林或其药学上可接受的盐方面有用的中间体化合物及其制备方法。
• Intermediates useful in the preparation of halichondrin compounds and methods for preparing the same
  申请人：BEIJING TIENYI LUFU PHARMATECH CO. LTD.

  公开号：US20210163509A1

  公开（公告）日：2021-06-03

  The invention relates to intermediates useful in the preparation of halichondrin compounds, methods for preparing the same and use thereof, such as halichondrins, eribulin, or their analogs. The intermediates, the methods and use thereof are used for the synthesis of the C20-C26 fragment of halichondrin compounds. The raw materials in the synthetic route of the invention are cheap and easily obtained, the sources and the qualities of the raw materials are reliable. The choice of the methods useful in the synthesis of chiral central structures are based on the structural characteristics of the reactants, thus effectively improving the synthesis efficiency, reducing the difficulties and risks of product quality control, and avoiding the use of highly toxic and expensive organotin catalysts to significantly decrease costs and improve environmental friendliness.
• Dramatic Improvement in Catalyst Loadings and Molar Ratios of Coupling Partners for Ni/Cr-Mediated Coupling Reactions: Heterobimetallic Catalysts
  作者：Xiang Liu、James A. Henderson、Takeo Sasaki、Yoshito Kishi

  DOI：10.1021/ja9079308

  日期：2009.11.25

  Two new ligands 1a,b are reported. Upon treatment with 1 equiv of NiCl2 center dot(MeOCH2)(2), 1a,b give the corresponding Ni complexes. X-ray analysis of 1a-NiCl2 established that the NiCl2 is selectively coordinated to the phenanthroline nitrogens. Ni/Cr heterobimetallic catalysts 1a,b center dot CrCl2/NiCl2, prepared from 1a,b center dot NiCl2, have been shown to behave exceptionally well in catalytic asymmetric Ni/Cr-mediated couplings, with highlights including the following: (1) 1-2 mol % catalyst is sufficient to complete the coupling; (2) only negligible amounts of the dimers, byproducts formed through the alkenyl Ni species, are observed; (3) the coupling goes to completion even with a 1:1 molar ratio of the coupling partners; and (4) the asymmetric induction is practically identical with that obtained from the coupling with the Cr catalysts prepared from (S)-sulfonamides 2a,b. The scope of the new Ni/Cr heterobimetallic catalysts was briefly studied using four additional aldehydes. The applicability of the new catalysts to polyfunctional substrates was demonstrated by two C-C bond formations chosen from the hatichondrin/E7389 synthesis as examples.
• New Syntheses of E7389 C14−C35 and Halichondrin C14−C38 Building Blocks: Reductive Cyclization and Oxy-Michael Cyclization Approaches
  作者：Cheng-Guo Dong、James A. Henderson、Yosuke Kaburagi、Takeo Sasaki、Dae-Shik Kim、Joseph T. Kim、Daisuke Urabe、Haibing Guo、Yoshito Kishi

  DOI：10.1021/ja9058487

  日期：2009.11.4

  coupling partners. The C23-O bond is stereospecifically constructed via reductive cyclization of the oxonium ion, or oxy-Michael cyclization. Both syntheses have a high overall efficiency: E7389 C14-C35 and halichondrin C14-C38 building blocks have been synthesized from the corresponding C27-C35 and C27-C38 aldehydes, respectively, in high overall yields with an excellent stereoselectivity. Because of

  Cr 介导的偶联反应通常在给定亲核试剂略微过量的情况下实现。为了开发该过程的经济有效的使用，已经研究了两种不同的方法。第一种方法依赖于两个连续的催化不对称 Cr 介导的偶联，偶联伙伴的使用有意使分子大小和复杂性不平衡。第二种方法依赖于确定亲核试剂的成功，这使我们能够以 1:1 的偶联伙伴摩尔比令人满意地实现偶联。C23-O 键是通过氧鎓离子的还原环化或氧-迈克尔环化立体有择地构建的。两种合成都具有较高的整体效率：E7389 C14-C35 和软海绵素 C14-C38 构建块已由相应的 C27-C35 和 C27-C38 醛合成，分别以高总产率和优异的立体选择性。由于操作简单，本文概述的合成似乎非常适合缩放。