spliceostatin A | 391611-36-2

• 物质功能分类: 医药中间体 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: spliceostatin A
• 英文别名: [(Z,2S)-5-[[(2R,3R,5S,6S)-6-[(2E,4E)-5-[(3R,4R,5R,7S)-4-hydroxy-7-methoxy-7-methyl-1,6-dioxaspiro[2.5]octan-5-yl]-3-methylpenta-2,4-dienyl]-2,5-dimethyloxan-3-yl]amino]-5-oxopent-3-en-2-yl] acetate
• CAS: 391611-36-2
• 化学式: C₂₈H₄₃NO₈
• 分子量: 521.651
• InChiKey: XKSGIJNRMWHQIQ-CGPJBNNXSA-N

物化性质

• 熔点：
  65-70 °C
• 沸点：
  683.2±55.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  spliceostatin A 在 咪唑 、 4-二甲氨基吡啶 、 四丁基氟化铵 、 potassium carbonate 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 7-(9H-fluoren-9-ylmethoxycarbonylamino)-heptanoic acid 3-{6-[5-(4-hydroxy-7-methoxy-7-methyl-1,6-dioxa-spiro[2.5]oct-5-yl)-3-methyl-penta-2,4-dienyl]-2,5-dimethyl-tetrahydro-pyran-3-ylcarbamoyl}-1-methyl-allyl ester
  参考文献：
  名称：

  Synthesis of Affinity Nanoparticles Coupled to FR901464 Derivatives

  摘要：

  DOI：

  10.3987/com-04-s(p)31
• 作为产物：
  描述：

  Acetic acid (Z)-(S)-3-{(2R,3R,5S,6S)-6-[(2E,4E)-5-((2R,3S,6S)-3-hydroxy-6-methoxy-6-methyl-4-methylene-tetrahydro-pyran-2-yl)-3-methyl-penta-2,4-dienyl]-2,5-dimethyl-tetrahydro-pyran-3-ylcarbamoyl}-1-methyl-allyl ester 在 碳酸氢钠 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 以23%的产率得到spliceostatin A
  参考文献：
  名称：

  A synthesis of FR901464

  摘要：

  FR901464, a potent cell cycle inhibitor, was synthesized in a convergent manner using natural chiral Pool, L-threonine, ethyl (S)-lactate and 2-deoxy-D-glucose as starting materials. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(01)01763-4

文献信息

• Enantioselective Total Syntheses of FR901464 and Spliceostatin A and Evaluation of Splicing Activity of Key Derivatives
  作者：Arun K. Ghosh、Zhi-Hua Chen、Kerstin A. Effenberger、Melissa S. Jurica

  DOI：10.1021/jo500800k

  日期：2014.6.20

  multiple human cancer cell lines. Herein, we describe efficient, enantioselective syntheses of FR901464, spliceostatin A, six corresponding diastereomers and an evaluation of their splicing activity. Syntheses of spliceostatin A and FR901464 were carried out in the longest linear sequence of 9 and 10 steps, respectively. To construct the highly functionalized tetrahydropyran A-ring, we utilized CBS reduction

  FR901464 ( 1 ) 和剪接抑制素A ( 2 ) 是剪接体的有效抑制剂。这些化合物对多种人类癌细胞系显示出显着的抗癌活性。在此，我们描述了 FR901464、剪接抑制素 A、六种相应的非对映异构体的高效对映选择性合成及其剪接活性的评估。剪接抑制素 A 和 FR901464 的合成分别以最长的 9 步和 10 步线性序列进行。构建高度官能化的四氢吡喃A-ring，我们利用 CBS 还原、Achmatowicz 重排、迈克尔加成和还原胺化作为关键步骤。迈克尔加成的显着非对映选择性在各种反应条件下用不同的底物得到了具体证明。侧链B由旋光醇制备，然后在 Lindlar 催化剂上乙酰化和氢化。另一个密集官能化的四氢吡喃C环来自现成的 ( R)-异亚丙基甘油醛通过以 1,2-加成、环状缩酮化和区域选择性环氧化为特征的路线。这些片段在后期通过酰胺化和交叉复分解以收敛的方式耦合在一起。然后合成了六个关键的非对映异构体，以探讨
• Structure-activity Relationship for FR901464: A Versatile Method for the Conversion and Preparation of Biologically Active Biotinylated Probes
  作者：Hajime MOTOYOSHI、Masato HORIGOME、Ken ISHIGAMI、Tatsuhiko YOSHIDA、Sueharu HORINOUCHI、Minoru YOSHIDA、Hidenori WATANABE、Takeshi KITAHARA

  DOI：10.1271/bbb.68.2178

  日期：2004.1

  The structure-activity relationship for FR901464, a potent cell-cycle inhibitor, was examined by synthesizing its analogs. A versatile method for converting FR901464 was devised. This method made it possible to synthesize biologically active FR901464-biotin conjugates which could be used to isolate the binding proteins.

  FR901464（一种有效的细胞周期抑制剂）的结构-活性关系通过合成其类似物进行了检查。设计了一种转换 FR901464 的通用方法。该方法使得合成具有生物活性的 FR901464-生物素缀合物成为可能，该缀合物可用于分离结合蛋白。
• Anti-cancer agents and preparation thereof
  申请人：Purdue Research Foundation

  公开号：US10000505B2

  公开（公告）日：2018-06-19

  Embodiments of the present invention provide, among other compounds, a family of spliceosome-inhibiting compounds that can be used as therapeutic anti-cancer agents. The compounds are synthesized in a process that includes the catalytic cross metathesis of a cyclic epoxy alcohol to an amide.

  除其他化合物外，本发明的实施方案还提供了一系列可用作治疗性抗癌剂的剪接体抑制化合物。这些化合物的合成过程包括环状环氧醇与酰胺的催化交叉偏析。
• Enantioselective Syntheses of FR901464 and Spliceostatin A: Potent Inhibitors of Spliceosome
  作者：Arun K. Ghosh、Zhi-Hua Chen

  DOI：10.1021/ol4024634

  日期：2013.10.4

  Enantioselective syntheses of FR901464 and spliceostatin A, potent spliceosome inhibitors, are described. The synthesis of FR901464 has been accomplished in a convergent manner in 10 linear steps (20 total steps). The A-tetrahydropyran ring was constructed from (R)-isopropylidene glyceraldehyde. The functionalized tetrahydropyran B-ring was synthesized utilizing a Corey-Bakshi-Shibata reduction, an Achmatowicz reaction, and a stereoselective Michael addition as the key steps. Coupling of A- and B-ring fragments was accomplished via cross-metathesis.
• Total synthesis of FR901464: second generation
  作者：Hajime Motoyoshi、Masato Horigome、Hidenori Watanabe、Takeshi Kitahara

  DOI：10.1016/j.tet.2005.11.031

  日期：2006.2

  FR901464, a potent cell cycle inhibitor, was synthesized in a convergent manner using natural chiral Pool, L-threonine, ethyl (S)-lactate and 2-deoxy-D-glucose as starting materials. (c) 2005 Published by Elsevier Ltd.