2-trimethylsilylethyl (2S)-2-[[(2S,3R)-2-amino-3-hydroxybutanoyl]amino]-3-methylbutanoate | 1089192-71-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-trimethylsilylethyl (2S)-2-[[(2S,3R)-2-amino-3-hydroxybutanoyl]amino]-3-methylbutanoate
• CAS: 1089192-71-1
• 化学式: C₁₄H₃₀N₂O₄Si
• 分子量: 318.489
• InChiKey: AVISJIJSQFUOJX-WOPDTQHZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.72
• 重原子数：
  21
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  102
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-trimethylsilylethyl (2S)-2-[[(2S,3R)-2-amino-3-hydroxybutanoyl]amino]-3-methylbutanoate 、 N-Fmoc-S-三苯甲基-D-半胱氨酸 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 以6.98 g的产率得到(S)-2-{(2S,3R)-2-[(S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-tritylsulfanyl-propionylamino]-3-hydroxy-butyrylamino}-3-methyl-butyric acid 2-trimethylsilanyl-ethyl ester
  参考文献：
  名称：

  Macrolactamization versus Macrolactonization: Total Synthesis of FK228, the Depsipeptide Histone Deacetylase Inhibitor

  摘要：

  The cyclic depsipeptide FK228 is the only natural product histone deacetylase (HDAC) inhibitor that has advanced to clinical trials Lis an anticancer agent. While currently obtained by fermentation, total synthesis is in attractive alternative that will facilitate the preparation of unnatural analogues. The previous total syntheses of FK228 featured macrocylization by ester bond formation from a seco-hydroxy acid. Such routes are operationally jeopardized by the steric hindrance of the carboxylic acid and the sensitivity of the allylic alcohol toward elimination. We report a strategically different approach whereby the ester bond is formed intermolecularly at an early stage and macrocyclization is efficiently achieved by amide bond formation.

  DOI：

  10.1021/jo801866z
• 作为产物：
  描述：

  (S)-2-[(2S,3R)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-hydroxy-butyrylamino]-3-methyl-butyric acid 2-trimethylsilanyl-ethyl ester 在 二乙胺 作用下， 以 乙腈 为溶剂， 反应 4.0h， 生成 2-trimethylsilylethyl (2S)-2-[[(2S,3R)-2-amino-3-hydroxybutanoyl]amino]-3-methylbutanoate
  参考文献：
  名称：

  Macrolactamization versus Macrolactonization: Total Synthesis of FK228, the Depsipeptide Histone Deacetylase Inhibitor

  摘要：

  The cyclic depsipeptide FK228 is the only natural product histone deacetylase (HDAC) inhibitor that has advanced to clinical trials Lis an anticancer agent. While currently obtained by fermentation, total synthesis is in attractive alternative that will facilitate the preparation of unnatural analogues. The previous total syntheses of FK228 featured macrocylization by ester bond formation from a seco-hydroxy acid. Such routes are operationally jeopardized by the steric hindrance of the carboxylic acid and the sensitivity of the allylic alcohol toward elimination. We report a strategically different approach whereby the ester bond is formed intermolecularly at an early stage and macrocyclization is efficiently achieved by amide bond formation.

  DOI：

  10.1021/jo801866z

文献信息

• Macrolactamization versus Macrolactonization: Total Synthesis of FK228, the Depsipeptide Histone Deacetylase Inhibitor
  作者：Shijun Wen、Graham Packham、A. Ganesan

  DOI：10.1021/jo801866z

  日期：2008.12.5

  The cyclic depsipeptide FK228 is the only natural product histone deacetylase (HDAC) inhibitor that has advanced to clinical trials Lis an anticancer agent. While currently obtained by fermentation, total synthesis is in attractive alternative that will facilitate the preparation of unnatural analogues. The previous total syntheses of FK228 featured macrocylization by ester bond formation from a seco-hydroxy acid. Such routes are operationally jeopardized by the steric hindrance of the carboxylic acid and the sensitivity of the allylic alcohol toward elimination. We report a strategically different approach whereby the ester bond is formed intermolecularly at an early stage and macrocyclization is efficiently achieved by amide bond formation.