(4R)-(+)-crassalactone D | 1190851-29-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (4R)-(+)-crassalactone D
• 英文别名: (5R,7R,8S)-8-hydroxy-7-phenyl-1,6-dioxaspiro[4.4]non-3-en-2-one
• CAS: 1190851-29-6
• 化学式: C₁₃H₁₂O₄
• 分子量: 232.236
• InChiKey: HQBGZDWOMDYFLH-CYZMBNFOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1,2-O-isopropylidene-5-C-phenyl-β-L-ido-pentofuranose 在 吡啶 、 偶氮二异丁腈 、 水 、 碘 、 三正丁基氢锡 、 sodium hydride 、 碳酸氢钠 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 、 乙腈 为溶剂， 反应 196.0h， 生成 (4R)-(+)-crassalactone D
  参考文献：
  名称：

  Synthesis and antiproliferative activity of goniobutenolides A and B, 5-halogenated crassalactone D derivatives and the corresponding 7-epimers

  摘要：

  A new synthesis of goniobutenolides A (1) and B (2) and the corresponding 7-epimers has been achieved starting from diacetone D-glucose. The key step of the synthesis is a new one-pot sequence that commenced with Z-selective Wittig (or Horner-Wadsworth-Emmons) olefination, followed by successive gamma-lactonisation and beta-elimination. The above-mentioned unsaturated lactones were then converted to the corresponding 5-halogenated crassalactone D derivatives by using the appropriate haloetherification protocol. The most of synthesized compounds exhibited potent cytotoxic activities against a panel of tumour cell lines. The main structural features responsible for their antitumour potency have been revealed by means of SAR analysis. Flow cytometry data suggested that cytotoxic effects of these compounds in the culture of K562 cells might be mediated by apoptosis, additionally revealing that these molecules induced changes in cell cycle distribution of these cells. Results of semi-quantitative Western blot analysis indicate that the most of synthesized compounds induce apoptosis in a caspase-dependent manner. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.12.011

文献信息

• Divergent Synthesis of Cytotoxic Styryl Lactones Related to Goniobutenolides A and B, and to Crassalactone D
  作者：Velimir Popsavin、Ivana Kovačević、Goran Benedeković、Mirjana Popsavin、Vesna Kojić、Gordana Bogdanović

  DOI：10.1021/ol302860z

  日期：2012.12.7

  Goniobutenolides A (1) and B (2), crassalactone D (3), 4-epi-crassalactone D (4), and the corresponding 7-epimers have been synthesized starting from d-glucose. The key step in the synthesis of 1 and 2 is a new one-pot sequence comprised of a Z-selective Wittig olefination/lactonization/β-elimination. Preparation of 3 and 4 included the final 5-endo-trig spirocyclization of 1 and 2. The synthesized

  从d-葡萄糖开始合成了Goniobutenolides A（1）和B（2），crassalactone D（3），4- epi- crassalactone D（4）和相应的7表位受体。合成1和2的关键步骤是一个新的一锅法序列，该序列由Z选择性维蒂希烯化/内酯化/β-消除反应组成。3和4的制备包括1和2的最终5-内-trig螺环化。评价合成产物对所选肿瘤细胞系的体外抗增殖活性。
• Synthesis and in vitro antitumour activity of crassalactone D, its stereoisomers and novel cinnamic ester derivatives
  作者：Ivana Kovačević、Mirjana Popsavin、Goran Benedeković、Jelena Kesić、Vesna Kojić、Dimitar Jakimov、Tatjana Srdić-Rajić、Gordana Bogdanović、Vladimir Divjaković、Velimir Popsavin

  DOI：10.1016/j.ejmech.2017.03.088

  日期：2017.7

  Naturally occurring styryl lactone, crassalactone D (1), unnatural 4-epi-crassalactone D (2), and the corresponding 7-epimers (3 and 4) have been synthesized starting from d-glucose. The key step of the synthesis is a new one-pot sequence that commenced with a Z-selective Wittig olefination of suitably functionalized sugar lactols with a stabilized ylide, (methoxycarbonylmethylene)-triphenylphosphorane

  从d-葡萄糖开始合成了天然存在的苯乙烯基内酯，crassalactone D（1），非天然的4-ep-crassalactone D（2）和相应的7-表位（3和4）。合成的关键步骤是一个新的一锅法序列，该序列首先在适当的官能化糖乳糖醇与Z选择性Wittig烯烃与稳定的内酯，（甲氧基羰基亚甲基）-三苯基膦烷的无水甲醇中进行烯化，以得到1或3。与相应的4受体（分别为2或4）的混合物。已经制备了许多苯乙烯基内酯1-4的6-O-肉桂酰基衍生物，它们在肉桂酸残基的C-4位具有给电子或吸电子功能。评估了合成产物对选定的人类肿瘤细胞系的体外抗增殖活性，因此，在许多情况下都记录了非常强的细胞毒性。SAR分析表明，一些重要的生物活性结构特征，例如C-4和C-7位置的立体化学，以及肉桂酸酯部分芳环C-4位置的取代基的性质。流式细胞仪和蛋白质印迹分析数据提供了对合成化合物抗增殖作用的潜在机制的深入了解。
• Synthesis and antiproliferative activity of goniobutenolides A and B, 5-halogenated crassalactone D derivatives and the corresponding 7-epimers
  作者：Ivana Kovačević、Mirjana Popsavin、Goran Benedeković、Vesna Kojić、Dimitar Jakimov、Marko V. Rodić、Tatjana Srdić-Rajić、Gordana Bogdanović、Vladimir Divjaković、Velimir Popsavin

  DOI：10.1016/j.ejmech.2015.12.011

  日期：2016.1

  A new synthesis of goniobutenolides A (1) and B (2) and the corresponding 7-epimers has been achieved starting from diacetone D-glucose. The key step of the synthesis is a new one-pot sequence that commenced with Z-selective Wittig (or Horner-Wadsworth-Emmons) olefination, followed by successive gamma-lactonisation and beta-elimination. The above-mentioned unsaturated lactones were then converted to the corresponding 5-halogenated crassalactone D derivatives by using the appropriate haloetherification protocol. The most of synthesized compounds exhibited potent cytotoxic activities against a panel of tumour cell lines. The main structural features responsible for their antitumour potency have been revealed by means of SAR analysis. Flow cytometry data suggested that cytotoxic effects of these compounds in the culture of K562 cells might be mediated by apoptosis, additionally revealing that these molecules induced changes in cell cycle distribution of these cells. Results of semi-quantitative Western blot analysis indicate that the most of synthesized compounds induce apoptosis in a caspase-dependent manner. (C) 2015 Elsevier Masson SAS. All rights reserved.