(1S,3R,11R,14S)-14-(hydroxymethyl)-3-[(1S,3R,11R,14S)-14-(hydroxymethyl)-15-methyl-13,16-dioxo-17-thia-10,12,15-triazapentacyclo[12.2.1.01,12.03,11.04,9]heptadeca-4,6,8-trien-3-yl]-15-methyl-17-thia-10,12,15-triazapentacyclo[12.2.1.01,12.03,11.04,9]heptadeca-4,6,8-triene-13,16-dione | 118101-83-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (1S,3R,11R,14S)-14-(hydroxymethyl)-3-[(1S,3R,11R,14S)-14-(hydroxymethyl)-15-methyl-13,16-dioxo-17-thia-10,12,15-triazapentacyclo[12.2.1.01,12.03,11.04,9]heptadeca-4,6,8-trien-3-yl]-15-methyl-17-thia-10,12,15-triazapentacyclo[12.2.1.01,12.03,11.04,9]heptadeca-4,6,8-triene-13,16-dione
• CAS: 118101-83-0
• 化学式: C₃₀H₂₈N₆O₆S₂
• 分子量: 632.721
• InChiKey: GTWBRYPJUZEXNW-PNVYSBBASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  44
• 可旋转键数：
  3
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  196
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  毛壳素 在 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以93%的产率得到(1S,3R,11R,14S)-14-(hydroxymethyl)-3-[(1S,3R,11R,14S)-14-(hydroxymethyl)-15-methyl-13,16-dioxo-17-thia-10,12,15-triazapentacyclo[12.2.1.01,12.03,11.04,9]heptadeca-4,6,8-trien-3-yl]-15-methyl-17-thia-10,12,15-triazapentacyclo[12.2.1.01,12.03,11.04,9]heptadeca-4,6,8-triene-13,16-dione
  参考文献：
  名称：

  手性光谱法测定半合成天然产物类似物的立体化学：桥二硫二氧代哌嗪真菌代谢物的脱硫

  摘要：

  真菌代谢物毛壳素的分离和半合成修饰获得了这种天然产物的脱硫类似物。详细的手性光学研究，将实验获得的旋光值、电子圆二色光谱和振动圆二色光谱与计算模拟的光谱进行比较，揭示了毛壳素的脱硫过程在保持构型的情况下明确进行。对该过程的合理机制的考虑强调了文献中相关分子的立体化学分配的不一致。这反过来又允许天然产物类似物脱硫脱氢胶质毒素的立体化学重新分配。

  DOI：

  10.1002/chem.201101129

文献信息

• On the Determination of the Stereochemistry of Semisynthetic Natural Product Analogues using Chiroptical Spectroscopy: Desulfurization of Epidithiodioxopiperazine Fungal Metabolites
  作者：Fanny Cherblanc、Ya-Pei Lo、Ewoud De Gussem、Laura Alcazar-Fuoli、Elaine Bignell、Yanan He、Nadine Chapman-Rothe、Patrick Bultinck、Wouter A. Herrebout、Robert Brown、Henry S. Rzepa、Matthew J. Fuchter

  DOI：10.1002/chem.201101129

  日期：2011.10.10

  Isolation and semisynthetic modification of the fungal metabolite chaetocin gave access to a desulfurized analogue of this natural product. Detailed chiroptical studies, comparing experimentally obtained optical rotation values, electronic circular dichroism spectra, and vibrational circular dichroism spectra to computationally simulated ones, reveal the desulfurization of chaetocin to unambiguously

  真菌代谢物毛壳素的分离和半合成修饰获得了这种天然产物的脱硫类似物。详细的手性光学研究，将实验获得的旋光值、电子圆二色光谱和振动圆二色光谱与计算模拟的光谱进行比较，揭示了毛壳素的脱硫过程在保持构型的情况下明确进行。对该过程的合理机制的考虑强调了文献中相关分子的立体化学分配的不一致。这反过来又允许天然产物类似物脱硫脱氢胶质毒素的立体化学重新分配。
• Epidithiodiketopiperazine as a pharmacophore for protein lysine methyltransferase G9a inhibitors: Reducing cytotoxicity by structural simplification
  作者：Shinya Fujishiro、Kosuke Dodo、Eriko Iwasa、Yuou Teng、Yoshihiro Sohtome、Yoshitaka Hamashima、Akihiro Ito、Minoru Yoshida、Mikiko Sodeoka

  DOI：10.1016/j.bmcl.2012.11.087

  日期：2013.2

  Chaetocin (1), a structurally complex epidithiodiketopiperazine (ETP) alkaloid produced by Chaetomium minutum, is a potent inhibitor of protein lysine methyltransferase G9a, which plays important roles in many biological processes. Here we present our synthetic investigations to identify a simple prototype G9a inhibitor structure based on structure-activity relationship (SAR) studies on chaetocin derivatives. The simple derivative PS-ETP-1 (14) was found to be a potent G9a inhibitor with greatly reduced cytotoxicity. (c) 2012 Elsevier Ltd. All rights reserved.
• SAITO, TAKAO;SUZUKI, YASUSHI;KOYAMA, KIYOTAKA;NATORI, SHINSAKU;IITAKA, YO+, CHEM. AND PHARM. BULL., 36,(1988) N 6, C. 1942-1956
  作者：SAITO, TAKAO、SUZUKI, YASUSHI、KOYAMA, KIYOTAKA、NATORI, SHINSAKU、IITAKA, YO+

  DOI：——

  日期：——
• On the Histone Lysine Methyltransferase Activity of Fungal Metabolite Chaetocin
  作者：Fanny L. Cherblanc、Kathryn L. Chapman、Jim Reid、Aaron J. Borg、Sandeep Sundriyal、Laura Alcazar-Fuoli、Elaine Bignell、Marina Demetriades、Christopher J. Schofield、Peter A. DiMaggio、Robert Brown、Matthew J. Fuchter

  DOI：10.1021/jm401063r

  日期：2013.11.14

  Histone lysine methyltransferases (HKMTs) are an important class of targets for epigenetic therapy. 1 (chaetocin), an epidithiodiketopiperazine (ETP) natural product, has been reported to be a specific inhibitor of the SU(VAR)3-9 class of HKMTs. We have studied the inhibition of the HKMT G9a by 1 and functionally related analogues. Our results reveal that only the structurally unique ETP core is required for inhibition, and such inhibition is time-dependent and irreversible (in the absence of DTT), ultimately resulting in protein denaturation. Mass spectrometric data provide a molecular basis for this effect, demonstrating covalent adduct formation between 1 and the protein. This provides a potential rationale for the selectivity observed in the inhibition of a variety of HKMTs by 1 in vitro and has implications for the activity of ETPs against these important epigenetic targets.