[2-hydroxy-3-methoxy-6-[(E)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenyl] 4-methylbenzenesulfonate | 1231184-93-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: [2-hydroxy-3-methoxy-6-[(E)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenyl] 4-methylbenzenesulfonate
• CAS: 1231184-93-2
• 化学式: C₂₅H₂₆O₈S
• 分子量: 486.543
• InChiKey: IGHFUNKKIJQFNN-CMDGGOBGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  [2-hydroxy-3-methoxy-6-[(E)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenyl] 4-methylbenzenesulfonate 在 甲醇 、 四氯化碳 、 4-二甲氨基吡啶 、 三甲基溴硅烷 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 乙腈 为溶剂， 反应 3.5h， 生成 (E)-1-[3',4',5'-trimethoxyphenyl]-2-[2"-hydroxy-3"-[(disodium)phosphate]-4"-methoxyphenyl]ethene
  参考文献：
  名称：

  Regioselective Synthesis of Water-Soluble Monophosphate Derivatives of Combretastatin A-1

  摘要：

  The natural products combretastatin A-4 (CA4) and combretastatin A-1 (CA1) are potent cancer vascular disrupting agents and inhibitors of tubulin assembly (IC50 = 1-2 mu M). The phosphorylated prodrugs CA4P and CA1P are undergoing human clinical trials against cancer. CA1 is unique due to its incorporation of a vicinal phenol, which has afforded the opportunity to prepare both diphosphate and regioisomeric monophosphate derivatives. Here, we describe the first synthetic routes suitable for the regiospecific preparation of the CA1-monophosphates CA1MPA (8a/b) and CA1MPB (4a/b). The essential regio chemistry necessary to distinguish between the two vicinal phenolic groups was accomplished with a tosyl protecting group strategy. Each of the four monophosphate analogues (including Z and E isomers) demonstrated in vitro cytotoxicity against selected human cancer cell lines comparable to their corresponding diphosphate congeners. Furthermore, Z-CA1MPA (8a) and Z-CA1MPB (4a) were inactive as inhibitors of tubulin assembly (Ic(50) > 40 mu M), as anticipated in this pure protein assay.

  DOI：

  10.1021/np200104t
• 作为产物：
  描述：

  [2-[tert-butyl(dimethyl)silyl]oxy-3-methoxy-6-[(E)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenyl] 4-methylbenzenesulfonate 在 potassium fluoride 、 氢溴酸 作用下， 以 N,N-二甲基甲酰胺 、 水 为溶剂， 反应 1.0h， 以82%的产率得到[2-hydroxy-3-methoxy-6-[(E)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenyl] 4-methylbenzenesulfonate
  参考文献：
  名称：

  Regio- and Stereospecific Synthesis of Mono-β-d-Glucuronic Acid Derivatives of Combretastatin A-1

  摘要：

  Synthetic routes have been established for the preparation of regio- and stereoisomerically pure samples of the mono-beta-D-glucuronic acid derivatives of combretastatin A-1, referred to as CA1G1 (5a) and CA1G2 (6a). Judicious choice of protecting groups for the catechol ring was required for the regiospecific introduction of the glucuronic acid moiety. The tosyl group proved advantageous in this regard. The two monoglucuronic acid analogues demonstrate low cytotoxicity (compared to CA1, 2) against selected human cancer cell lines, with CA1G1 being slightly more potent than CA1G2.

  DOI：

  10.1021/np100108e

文献信息

• Regio- and Stereospecific Synthesis of Mono-β-<scp>d</scp>-Glucuronic Acid Derivatives of Combretastatin A-1
  作者：Rajendra P. Tanpure、Tracy E. Strecker、David J. Chaplin、Bronwyn G. Siim、Mary Lynn Trawick、Kevin G. Pinney

  DOI：10.1021/np100108e

  日期：2010.6.25

  Synthetic routes have been established for the preparation of regio- and stereoisomerically pure samples of the mono-beta-D-glucuronic acid derivatives of combretastatin A-1, referred to as CA1G1 (5a) and CA1G2 (6a). Judicious choice of protecting groups for the catechol ring was required for the regiospecific introduction of the glucuronic acid moiety. The tosyl group proved advantageous in this regard. The two monoglucuronic acid analogues demonstrate low cytotoxicity (compared to CA1, 2) against selected human cancer cell lines, with CA1G1 being slightly more potent than CA1G2.
• Regioselective Synthesis of Water-Soluble Monophosphate Derivatives of Combretastatin A-1
  作者：Rajendra P. Tanpure、Benson L. Nguyen、Tracy E. Strecker、Savannah Aguirre、Suman Sharma、David J. Chaplin、Bronwyn G. Siim、Ernest Hamel、John W. Lippert、George R. Pettit、Mary Lynn Trawick、Kevin G. Pinney

  DOI：10.1021/np200104t

  日期：2011.7.22

  The natural products combretastatin A-4 (CA4) and combretastatin A-1 (CA1) are potent cancer vascular disrupting agents and inhibitors of tubulin assembly (IC50 = 1-2 mu M). The phosphorylated prodrugs CA4P and CA1P are undergoing human clinical trials against cancer. CA1 is unique due to its incorporation of a vicinal phenol, which has afforded the opportunity to prepare both diphosphate and regioisomeric monophosphate derivatives. Here, we describe the first synthetic routes suitable for the regiospecific preparation of the CA1-monophosphates CA1MPA (8a/b) and CA1MPB (4a/b). The essential regio chemistry necessary to distinguish between the two vicinal phenolic groups was accomplished with a tosyl protecting group strategy. Each of the four monophosphate analogues (including Z and E isomers) demonstrated in vitro cytotoxicity against selected human cancer cell lines comparable to their corresponding diphosphate congeners. Furthermore, Z-CA1MPA (8a) and Z-CA1MPB (4a) were inactive as inhibitors of tubulin assembly (Ic(50) > 40 mu M), as anticipated in this pure protein assay.