epi-4R-{2S-[2-(3R-hydroxy-7-tritylsulfanylhept-4E-enoylamino)propionylamino]-3-tritylsulfanylpropionylamino}-5R-methyl-3S-triisopropylsilanyloxyhexanoic acid | 663919-08-2

• 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: epi-4R-{2S-[2-(3R-hydroxy-7-tritylsulfanylhept-4E-enoylamino)propionylamino]-3-tritylsulfanylpropionylamino}-5R-methyl-3S-triisopropylsilanyloxyhexanoic acid
• CAS: 663919-08-2
• 化学式: C₆₇H₈₃N₃O₇S₂Si
• 分子量: 1134.63
• InChiKey: WLLHQELSKSIUIA-RWEIJYQQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  13.3
• 重原子数：
  80.0
• 可旋转键数：
  30.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  154.06
• 氢给体数：
  5.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  epi-4R-{2S-[2-(3R-hydroxy-7-tritylsulfanylhept-4E-enoylamino)propionylamino]-3-tritylsulfanylpropionylamino}-5R-methyl-3S-triisopropylsilanyloxyhexanoic acid 在 三氯(氯甲基)苯 、 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51%的产率得到12R-isopropyl-6R-methyl-13S-triisopropylsilanyloxy-2R-[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：

  epi-4R-{2S-[2-(3R-hydroxy-7-tritylsulfanylhept-4E-enoylamino)propionylamino]-3-tritylsulfanylpropionylamino}-5R-methyl-3S-triisopropylsilanyloxyhexanoic acid 2,2,2-trichloroethyl ester 在 ammonium acetate 、 锌 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 以72%的产率得到epi-4R-{2S-[2-(3R-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