4-O-[3″,4″-di-O-methyl-β-d-xylopyranosyl]diphyllin

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 木脂素苷
• 英文名称: 4-O-[3″,4″-di-O-methyl-β-d-xylopyranosyl]diphyllin
• 英文别名: cleistanthin A；9-(1,3-benzodioxol-5-yl)-4-[(2S,3R,4R,5R)-3-hydroxy-4,5-dimethoxyoxan-2-yl]oxy-6,7-dimethoxy-3H-benzo[f][2]benzofuran-1-one
• 化学式: C₂₈H₂₈O₁₁
• 分子量: 540.524
• InChiKey: FCOQWUOWHWHTJP-DZXBDMBVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  39
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  4-O-[3″,4″-di-O-methyl-β-d-xylopyranosyl]diphyllin 在 sodium hydroxide 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 4-O-[2"-O-[6-[N-piperidinyl]hexyl]-3",4"-di-O-methyl-β-D-xylopyranosyl]diphyllin
  参考文献：
  名称：

  Synthesis and bioevaluation of heterocyclic derivatives of Cleistanthin-A

  摘要：

  The vacuolar H+-ATPase (V-ATPase) was proposed as a key target for new strategies in cancer treatment recently. We have synthesized a novel class of derivatives of Cleistanthin-A bearing heterocyclic moieties. Most of these compounds displayed potent antiproliferative effects on four cancer cells at submicromolar concentration, and they have no cytotoxicity on normal WRL-68 cells at 200 nM. The most potent compound 3a has been shown to inhibit the activity of vacuolar H+-ATPase at submicromolar concentration, and it could also significantly decrease the cytosolic pH values in HepG2 cells. The current findings provide valuable insights for future development of novel V-ATPase inhibitors as anticancer agents. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.05.033
• 作为产物：
  描述：

  4-O-[2"-O-acetyl-3",4"-di-O-methyl-β-d-xylopyranosyl]diphyllin 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以81%的产率得到4-O-[3″,4″-di-O-methyl-β-d-xylopyranosyl]diphyllin
  参考文献：
  名称：

  Synthesis and identification of cytotoxic diphyllin glycosides as vacuolar H+-ATPase inhibitors

  摘要：

  The concise syntheses of two natural diphyllin glycosides Cleistanthin-A (CA), Cleistanthoside-A (CleA) and its derivative, Cleistanthoside-A tetraacetate (CleT), have been achieved. They were evaluated for their in vitro anti-proliferative activities against MCF-7, HeLa, HepG2, HCT-116, U251 cancer cell lines by MTT assay. Both of CA and CleT were anti-proliferative to these cancer cells at nanomolar concentrations. They have been shown to inhibit the activity of vacuolar H+-ATPase (V-ATPase) in HepG2 cells and neutralize the pH of lysosomes at nanomolar concentrations. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.06.002

文献信息

• PROCESS FOR THE SYNTHESIS OF CLEISTANTHIN
  申请人：Singh Om Vir

  公开号：US20120029179A1

  公开（公告）日：2012-02-02

  The present invention relates to a process for preparing compound of formula (I) that is Cleistanthin A. The process comprises the steps of reacting compound of formula (II) with compound of formula (III) in the presence of a first solvent, quarternary ammonium salt and first alkali to form compound of formula (IV). The compound of formula (IV) is further treated with a second solvent and a second alkali to form compound of formula (I). The present invention also relates to the preparation of salt of compound of formula (IV) that is Cleistanthin A acetate.

  本发明涉及一种制备化合物的方法，该化合物的化学式为(I)，即克莱斯坦A。该方法包括以下步骤：在第一溶剂、季铵盐和第一碱的存在下，将化合物的化学式为(II)的化合物与化学式为(III)的化合物反应，形成化学式为(IV)的化合物。将化学式为(IV)的化合物进一步用第二溶剂和第二碱处理，形成化学式为(I)的化合物。本发明还涉及制备化学式为(IV)的盐的方法，该盐即克莱斯坦A乙酸盐。
• Cytotoxic Arylnaphthalide Lignan Glycosides from the Aerial Parts of<i>Phyllanthus taxodiifolius</i>
  作者：Patoomratana Tuchinda、Anawat Kumkao、Manat Pohmakotr、Samaisukh Sophasan、Thawatchai Santisuk、Vichai Reutrakul

  DOI：10.1055/s-2005-873141

  日期：2006.11

  The arylnaphthalide lignan glycosides, taxodiifoloside (1), cleistanthoside A (2), cleistanthin A (3) and cleistanthin A methyl ether (4), together with a triterpene, glochidone (5), have been isolated from the aerial parts of Phyllanthus taxodiifolius. The structures were established using spectral and chemical methods. Compounds 3 and 4, as well as the derivatives 2a and 3a exhibited potent cytotoxic activities with GI50 values in the range of 10-7 - 10-9 M in five cultured mammalian cancer cell lines while the new compound 1 showed moderate activity (GI50 in the order of 10-6 M). Compounds 2 and 5 were inactive in all tested cell lines.

  从税斑叶壳斗树（Phyllanthus taxodiifolius）的地上部分中分离出了四种芳基萘酰木质素苷：税斑叶壳斗苷 (1)、清香苷 A (2)、清香素 A (3) 和清香素 A 甲基醚 (4)，以及一种三萜类化合物，奎胺 (5)。通过光谱和化学方法确定了它们的结构。化合物 3 和 4，以及衍生物 2a 和 3a 在五种培养的哺乳动物癌细胞系中表现出强效的细胞毒性活性，其 GI50 值在 10^-7 到 10^-9 M 范围内，而新化合物 1 显示出中等活性（GI50 约为 10^-6 M）。化合物 2 和 5 在所有测试的细胞系中均无活性。
• Synthesis and Evaluation of Cleistanthin A Derivatives as Potent Vacuolar H⁺-ATPase Inhibitors
  作者：Yu Zhao、Yapeng Lu、Jinlong Ma、Li Zhu

  DOI：10.1111/cbdd.12538

  日期：2015.10

  Twelve new glycosides and alkane derivatives of cleistanthin A were designed and synthesized. Their in vitro antiproliferative activity was investigated against HCT‐116, HepG2, A549, Hela tumor cell lines and HEK293 cell by MTT assay. Most of these compounds displayed antiproliferative effects on four cancer cells at submicromolar concentration, but they were less potent than cleistanthin A Moreover, they showed no antiproliferative effects on HEK293 cell at 200 nm. The most potent compounds, 3e and 4a, have been shown to inhibit the activity of vacuolar H+‐ATPase (V‐ATPase) and neutralize the pH of lysosomes at submicromolar concentrations.
• [EN] PROCESS FOR THE SYNTHESIS OF CLEISTANTHIN<br/>[FR] PROCÉDÉ DE SYNTHÈSE DE CLEISTANTHINE
  申请人：GODAVARI BIOREFINERIES LTD

  公开号：WO2010089778A2

  公开（公告）日：2010-08-12

  The present invention relates to a process for preparing compound of formula (I) that is Cleistanthin A. The process comprises the steps of reacting compound of formula (II) with compound of formula (III) in the presence of a first solvent, quarternary ammonium salt and first alkali to form compound of formula (IV). The compound of formula (IV) is further treated with a second solvent and a second alkali to form compound of formula (I). The present invention also relates to the preparation of salt of compound of formula (IV) that is Cleistanthin A acetate.
• Synthesis and identification of cytotoxic diphyllin glycosides as vacuolar H+-ATPase inhibitors
  作者：Zhitao Zhang、Jinlong Ma、Li Zhu、Yu Zhao

  DOI：10.1016/j.ejmech.2014.06.002

  日期：2014.7

  The concise syntheses of two natural diphyllin glycosides Cleistanthin-A (CA), Cleistanthoside-A (CleA) and its derivative, Cleistanthoside-A tetraacetate (CleT), have been achieved. They were evaluated for their in vitro anti-proliferative activities against MCF-7, HeLa, HepG2, HCT-116, U251 cancer cell lines by MTT assay. Both of CA and CleT were anti-proliferative to these cancer cells at nanomolar concentrations. They have been shown to inhibit the activity of vacuolar H+-ATPase (V-ATPase) in HepG2 cells and neutralize the pH of lysosomes at nanomolar concentrations. (C) 2014 Elsevier Masson SAS. All rights reserved.