(3S,4R)-4-((tert-Butoxycarbonyl)amino)-3-hydroxy-5-methylhexanoic acid | 245445-74-3

• 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: (3S,4R)-4-((tert-Butoxycarbonyl)amino)-3-hydroxy-5-methylhexanoic acid
• 英文别名: (3S,4R)-3-hydroxy-5-methyl-4-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoic acid
• CAS: 245445-74-3
• 化学式: C₁₂H₂₃NO₅
• 分子量: 261.318
• InChiKey: BZQOWFKRUIHRDH-WCBMZHEXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3S,4R)-4-((tert-Butoxycarbonyl)amino)-3-hydroxy-5-methylhexanoic acid 在 2,6-二甲基吡啶 、 4-二甲氨基吡啶 、 ammonium acetate 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 乙胺 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 47.83h， 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
• 作为产物：
  描述：

  (3S,4R)-4-(tert-butoxycarbonylamino)-3-hydroxy-5-methylhexanoic acid methyl ester 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 (3S,4R)-4-((tert-Butoxycarbonyl)amino)-3-hydroxy-5-methylhexanoic 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

文献信息

• A total synthesis of spiruchostatin A
  作者：Takayuki Doi、Yusuke Iijima、Kazuo Shin-ya、A. Ganesan、Takashi Takahashi

  DOI：10.1016/j.tetlet.2005.12.031

  日期：2006.2

  We achieved the total synthesis of the histone deacetylase inhibitor spiruchostatin A, as the prelude to the preparation of a combinatorial library of its analogues. Two key reactions were an asymmetric acetate aldol reaction using a Zr-enolate and macrolactonization Using the Shiina method. (c) 2005 Published by Elsevier Ltd.
• Total Synthesis of Spiruchostatin A, a Potent Histone Deacetylase Inhibitor
  作者：Alexander Yurek-George、Fay Habens、Matthew Brimmell、Graham Packham、A. Ganesan

  DOI：10.1021/ja039258q

  日期：2004.2.1

  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.