(4R,4aR,7R,7aR)-6,7-dihydroxy-4-phenyl-4a,6,7,7a-tetrahydro-4H-furo[3,2-d][1,3]dioxin-2-one | 1413282-41-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二恶烷
• 英文名称: (4R,4aR,7R,7aR)-6,7-dihydroxy-4-phenyl-4a,6,7,7a-tetrahydro-4H-furo[3,2-d][1,3]dioxin-2-one
• CAS: 1413282-41-3
• 化学式: C₁₂H₁₂O₆
• 分子量: 252.224
• InChiKey: MVDBNTAEFHGLDS-VZVZTSLSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  85.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (4R,4aR,7R,7aR)-6,7-dihydroxy-4-phenyl-4a,6,7,7a-tetrahydro-4H-furo[3,2-d][1,3]dioxin-2-one 在 N-氯代丁二酰亚胺 、 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 92.0h， 生成 (4S,5R,7R)-5-chlorocrassalactone 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
• 作为产物：
  描述：

  1,2-O-isopropylidene-5-C-phenyl-β-L-ido-pentofuranose 在 水 、 三氟乙酸 作用下， 以 甲苯 为溶剂， 反应 3.5h， 生成 (4R,4aR,7R,7aR)-6,7-dihydroxy-4-phenyl-4a,6,7,7a-tetrahydro-4H-furo[3,2-d][1,3]dioxin-2-one
  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。
• Asymmetric synthesis and biological evaluation of (+)-cardiobutanolide, (−)-3-deoxycardiobutanolide and analogues as antiproliferative agents
  作者：Ivana Kovačević、Jelena Kesić、Mirjana Popsavin、Jovana Francuz、Vesna Kojić、Dimitar Jakimov、Marko V. Rodić、Bojana Srećo Zelenović、Goran Benedeković、Velimir Popsavin

  DOI：10.1016/j.tet.2021.132408

  日期：2021.9

  were synthesized in several steps that included zinc-mediated THF ring opening, subsequent stereoselective olefination, and final Sharpless asymmetric dihydroxylation. In vitro antitumour activities of these compounds were evaluated against a panel of eight human tumour cell lines and one normal cell line. Some of compounds displayed powerful effects against tumour cells, but none of them were active

  两种天然产物（+）-心丁内酯和（-）-3-脱氧心丁内酯以及五种新的类似物通过几个步骤合成，包括锌介导的 THF 开环、随后的立体选择性烯化和最终的 Sharpless 不对称二羟基化。体外针对一组八种人类肿瘤细胞系和一种正常细胞系评估了这些化合物的抗肿瘤活性。一些化合物对肿瘤细胞显示出强大的作用，但没有一种化合物对正常细胞有活性。一项 SAR 研究表明，(+)-心丁内酯的 C-6 和 C-7 位置的构型变化会降低类似物的抗肿瘤活性。C-3 位羟基的存在似乎也增加了这类内酯的活性。构象刚性内酯 goniofufurone 的活性与更灵活的心丁内酯和 3-脱氧心丁内酯的活性的比较表明空间灵活性对细胞毒性有积极影响。还证实去除苯基可产生更高活性的类似物。流式细胞术分析显示合成的化合物不诱导K562细胞的凋亡和坏死。然而，蛋白质印迹分析表明，除一种外，所有化合物都具有增加的 Bax/Bcl-2 蛋白表达比。
• 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。