4R-{2S-[2-(3S-hydroxy-7-tritylsulfanylhept-4E-enoylamino)propionylamino]-3-tritylsulfanylpropionylamino}-5R-methyl-3S-triisopropylsilanyloxyhexanoic acid | 663919-04-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: 4R-{2S-[2-(3S-hydroxy-7-tritylsulfanylhept-4E-enoylamino)propionylamino]-3-tritylsulfanylpropionylamino}-5R-methyl-3S-triisopropylsilanyloxyhexanoic acid
• 英文别名: (3S,4R)-4-[[(2S)-2-[[(2R)-2-[[(E,3S)-3-hydroxy-7-tritylsulfanylhept-4-enoyl]amino]propanoyl]amino]-3-tritylsulfanylpropanoyl]amino]-5-methyl-3-tri(propan-2-yl)silyloxyhexanoic acid
• CAS: 663919-04-8
• 化学式: C₆₇H₈₃N₃O₇S₂Si
• 分子量: 1134.63
• InChiKey: WLLHQELSKSIUIA-RTONAKIBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  13.3
• 重原子数：
  80
• 可旋转键数：
  30
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  205
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4R-{2S-[2-(3S-hydroxy-7-tritylsulfanylhept-4E-enoylamino)propionylamino]-3-tritylsulfanylpropionylamino}-5R-methyl-3S-triisopropylsilanyloxyhexanoic acid 在 2,4,6-三氯苯甲酰氯 、 三乙胺 、 4-二甲氨基吡啶 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 6.0h， 以53%的产率得到2R-isopropyl-6R-methyl-13S-triisopropylsilanyloxy-2S-[4-(triphenyl-λ-sulfanyl)but-1E-enyl]-9S-tritylsulfanylmethyl-1-oxa-5,8,11-triazacyclopentadecane-4,7,10,15-tetraone
  参考文献：
  名称：

  Total Synthesis of Spiruchostatin A, a Potent Histone Deacetylase Inhibitor

  摘要：

  The total synthesis of spiruchostatin A was accomplished, unambiguously confirming its structure. Key steps included the use of the Nagao thiazolidinethione auxiliary for a diastereoselective acetate aldol reaction and as an activated acylating agent for amide formation, and macrolactonization by the Yamaguchi protocol. Spiruchostatin A is shown to have biological activity similar to that of FK228, a potent histone deacetylase (HDAC) inhibitor in clinical trials. The spiruchostatin A analogue, epimeric at the beta-hydroxy acid, is inactive, highlighting the importance of stereochemistry at this position for interactions with HDACs.

  DOI：

  10.1021/ja039258q
• 作为产物：
  描述：

  (3S,4E)-3-hydroxy-1-((4R)-4-isopropyl-2-thioxothiazolidin-3-yl)-7-tritylsulfanyl-hept-4-en-1-one 在 4-二甲氨基吡啶 、 ammonium acetate 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 12.0h， 生成 4R-{2S-[2-(3S-hydroxy-7-tritylsulfanylhept-4E-enoylamino)propionylamino]-3-tritylsulfanylpropionylamino}-5R-methyl-3S-triisopropylsilanyloxyhexanoic acid
  参考文献：
  名称：

  Total Synthesis of Spiruchostatin A, a Potent Histone Deacetylase Inhibitor

  摘要：

  The total synthesis of spiruchostatin A was accomplished, unambiguously confirming its structure. Key steps included the use of the Nagao thiazolidinethione auxiliary for a diastereoselective acetate aldol reaction and as an activated acylating agent for amide formation, and macrolactonization by the Yamaguchi protocol. Spiruchostatin A is shown to have biological activity similar to that of FK228, a potent histone deacetylase (HDAC) inhibitor in clinical trials. The spiruchostatin A analogue, epimeric at the beta-hydroxy acid, is inactive, highlighting the importance of stereochemistry at this position for interactions with HDACs.

  DOI：

  10.1021/ja039258q