spirohexenolide A | 1193347-22-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: spirohexenolide A
• 英文别名: (1E,5S,7S,10R,11E,13E,16R,17Z)-16-hydroxy-7,8,10,12-tetramethyl-4,20-dioxatetracyclo[16.2.2.12,5.05,10]tricosa-1,8,11,13,17,21-hexaene-3,23-dione
• CAS: 1193347-22-6
• 化学式: C₂₅H₂₈O₅
• 分子量: 408.494
• InChiKey: SWMOMSBFRQXQAA-DPMNTXOZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  30
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  spirohexenolide A 、 甲氧基-三氟甲基苯 在 吡啶 、 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 0.83h， 以40%的产率得到[(1E,5S,7S,10R,11E,13E,16R,17Z)-7,8,10,12-tetramethyl-3,23-dioxo-4,20-dioxatetracyclo[16.2.2.12,5.05,10]tricosa-1,8,11,13,17,21-hexaen-16-yl] (2R)-3,3,3-trifluoro-2-methoxy-2-phenylpropanoate
  参考文献：
  名称：

  Isolation, Structure Elucidation, and Antitumor Activity of Spirohexenolides A and B

  摘要：

  In this report, we describe the discovery of a pair of bioactive spirotetronates, spirohexenolides A (1) and B (2), that arose from the application of mutagenesis, clonal selection techniques, and media optimization to strains of Streptomyces platensis. The structures of spirohexenolides A (1) and B (2) were elucidated through X-ray crystallography and confirmed by 1D and 2D NMR Studies. Under all examined culture conditions, spirohexenolide A (1) was the major metabolite with traces of spirohexenolide B (2) arising in cultures containing increased loads of adsorbent resins. Spirohexenolide A (1) inhibited tumor cell growth with GI(50) values spanning from 0.1 to 17 mu M across the NO 60 cell line panel. An increased activity was observed in leukemia (GI(50) value of 254 nM in RPMI-8226 cells), lung cancer (GI(50) value of 191 nM in HOP-92 cells), and colon cancer (GI(50) value of 565 nM in SW-620 cells) tumor cells. Metabolite 1 was fluorescent and could be examined on it confocal fluorescent microscope with conventional laser excitation and filter sets. Time lapse imaging studies indicated that spirohexenolide A (1) was readily taken up by tumor cells, appearing through the cell immediately after closing and subcellularly localizing in the lysosomes. This activity, combined with a unique selectivity in NCI 60 cancer cell line screening, indicates that 1 warrants further chemotherapeutic evaluation.

  DOI：

  10.1021/jo901826d
• 作为产物：
  描述：

  在 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 以15 %的产率得到spirohexenolide A
  参考文献：
  名称：

  大环内的弯曲 π 共轭：螺己烯内酯 A 和 B 的不对称全合成

  摘要：

  首次报道了螺环酮酯聚酮化合物 spirohexenolides A 和 B 的不对称全合成。该合成的特点是先进行闭环复分解大环化，然后进行双脱水，以实现具有前所未有的变形非平面 1,3,5-三烯共轭的 C15 大环。

  DOI：

  10.1002/anie.202316259