4R-[2-(9H-fluoren-9-ylmethoxycarbonylamino)-3S-tritylsulfanylpropionylamino]-5-methyl-3-triisopropylsilanyloxyhexanoic acid 2,2,2-trichloroethyl ester | 663919-01-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 4R-[2-(9H-fluoren-9-ylmethoxycarbonylamino)-3S-tritylsulfanylpropionylamino]-5-methyl-3-triisopropylsilanyloxyhexanoic acid 2,2,2-trichloroethyl ester
• 英文别名: 2,2,2-trichloroethyl (3S,4R)-4-[[(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-tritylsulfanylpropanoyl]amino]-5-methyl-3-tri(propan-2-yl)silyloxyhexanoate
• CAS: 663919-01-5
• 化学式: C₅₅H₆₅Cl₃N₂O₆SSi
• 分子量: 1016.64
• InChiKey: DHNSKLCVGLKZFC-JMRUPYPPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  13.62
• 重原子数：
  68
• 可旋转键数：
  23
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4R-[2-(9H-fluoren-9-ylmethoxycarbonylamino)-3S-tritylsulfanylpropionylamino]-5-methyl-3-triisopropylsilanyloxyhexanoic acid 2,2,2-trichloroethyl ester 在 乙胺 作用下， 以 乙腈 为溶剂， 反应 3.0h， 生成
  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：

  在 2,6-二甲基吡啶 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.83h， 生成 4R-[2-(9H-fluoren-9-ylmethoxycarbonylamino)-3S-tritylsulfanylpropionylamino]-5-methyl-3-triisopropylsilanyloxyhexanoic acid 2,2,2-trichloroethyl ester
  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

文献信息

• Total Synthesis of Spiruchostatin A via Chemoselective Macrocyclization using an Accessible Enantiomerically Pure Latent Thioester
  作者：Nicole A. Calandra、Yim Ling Cheng、Kimberly A. Kocak、Justin S. Miller

  DOI：10.1021/ol900436f

  日期：2009.5.7

  HDAC inhibitor Spiruchostatin A was synthesized via a route that differs significantly from previously reported routes. The key step involves a latent thioester that initiates a chemoselective transformation similar to native chemical ligation to form the macrocyclic alanine−cysteine amide bond. The easily prepared latent thioester—the first such moiety reported in enantiomerically pure form—is designed

  HDAC抑制剂Spiruchostatin A的合成路线与以前报道的路线明显不同。关键步骤涉及潜在的硫酯，该硫酯引发类似于自然化学连接的化学选择性转化反应，形成大环丙氨酸-半胱氨酸酰胺键。易于制备的潜在硫代酯（第一个以对映体纯形式报告的此类部分）与侧链羧酸一起设计，用作固相连接剂，用于合成环状，含半胱氨酸的肽类物质。