(Z)-1-[3',4',5'-trimethoxyphenyl]-2-[2"-[(para-toluenesulfonyl)oxy]-3"-[([bis[(benzyl)oxy]]phosphoryl)oxy]-4"-methoxyphenyl]ethene | 1313379-60-0

• 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: (Z)-1-[3',4',5'-trimethoxyphenyl]-2-[2"-[(para-toluenesulfonyl)oxy]-3"-[([bis[(benzyl)oxy]]phosphoryl)oxy]-4"-methoxyphenyl]ethene
• 英文别名: [2-bis(phenylmethoxy)phosphoryloxy-3-methoxy-6-[(Z)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenyl] 4-methylbenzenesulfonate
• CAS: 1313379-60-0
• 化学式: C₃₉H₃₉O₁₁PS
• 分子量: 746.772
• InChiKey: CYHPSINLNRHMGZ-HNENSFHCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  52
• 可旋转键数：
  17
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  133
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (Z)-1-[3',4',5'-trimethoxyphenyl]-2-[2"-[(para-toluenesulfonyl)oxy]-3"-[([bis[(benzyl)oxy]]phosphoryl)oxy]-4"-methoxyphenyl]ethene 在 三甲基溴硅烷 、 sodium methylate 作用下， 以 乙腈 、 甲醇 为溶剂， 反应 3.0h， 以52%的产率得到(Z)-1-[3',4',5'-trimethoxyphenyl]-2-[2"-[(para-toluenesulfonyl)oxy]-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：

  (Z)-2-hydroxy-3-methoxy-6-(3,4,5-trimethoxystyryl)phenyl 4-methylbenzenesulfonate 、 亚磷酸二苄酯 在 四氯化碳 、 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 以67%的产率得到(Z)-1-[3',4',5'-trimethoxyphenyl]-2-[2"-[(para-toluenesulfonyl)oxy]-3"-[([bis[(benzyl)oxy]]phosphoryl)oxy]-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

文献信息

• 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.