Apicidin A | 183506-67-4

• 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: Apicidin A
• 英文别名: apicidin；cyclo[Aoda-Trp-Ile-D-Pip]；(3S,6S,9S,12R)-3-[(2S)-butan-2-yl]-6-(1H-indol-3-ylmethyl)-9-(6-oxooctyl)-1,4,7,10-tetrazabicyclo[10.4.0]hexadecane-2,5,8,11-tetrone
• CAS: 183506-67-4
• 化学式: C₃₃H₄₇N₅O₅
• 分子量: 593.767
• InChiKey: BHYPIIUJEQHYIP-YWVQAIGBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  43
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  141
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Apicidin A 在 臭氧 、 二甲基硫 、 potassium tert-butylate 作用下， 以 二氯甲烷 、 四氢呋喃 、 叔丁醇 为溶剂， 反应 1.17h， 以64%的产率得到(6S,9S,12S,14aR)-6-((S)-sec-Butyl)-9-(4-oxo-1,4-dihydro-quinolin-3-yl)-12-(6-oxo-octyl)-decahydro-4a,7,10,13-tetraaza-benzocyclododecene-5,8,11,14-tetraone
  参考文献：
  名称：

  Synthesis of Apicidin-Derived Quinolone Derivatives:  Parasite-Selective Histone Deacetylase Inhibitors and Antiproliferative Agents

  摘要：

  Apicidin's indole was efficiently converted into a series of N-substituted quinolone derivatives by indole N-alkylation followed by a two-step, one-pot, ozonolysis/aldol condensation protocol. The new quinolones exhibited good parasite selectivity and potency both at the level of their molecular target, histone deacetylase, and in their whole cell antiproliferative activity in vitro.

  DOI：

  10.1021/jm0001976
• 作为产物：
  描述：

  apicidin 在 palladium on activated charcoal 氢气 作用下， 生成 Apicidin A
  参考文献：
  名称：

  Probing the elusive catalytic activity of vertebrate class IIa histone deacetylases

  摘要：

  It has been widely debated whether class IIa HDACs have catalytic deacetylase activity, and whether this plays any part in controlling gene expression. Herein, it has been demonstrated that class IIa HDACs isolated from mammalian cells are contaminated with other deacetylases, but can be prepared cleanly in Escherichia coli. These bacteria preparations have weak but measurable deacetylase activity. The low efficiency can be restored either by: mutation of an active site histidine to tyrosine, or by the use of a non-acetylated lysine substrate, allowing the development of assays to identify class IIa HDAC inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.02.025

文献信息

• Synthesis of (S)-2-amino-8-oxodecanoic acid (Aoda) and apicidin A
  作者：Liyuan Mou、Gurdial Singh

  DOI：10.1016/s0040-4039(01)01331-4

  日期：2001.9

  The synthesis of (S)-2-amino-8-oxodecanoic acid, a constituent of the cyclic tetrapeptides, the apicidins, was accomplished under photolytic conditions in the presence of tri-n-butyltin hydride using glutamic acid. This enabled a total synthesis of apicidin A to be completed.

  的合成（小号）-2-氨基-8- oxodecanoic酸时，环状四肽的组成部分，apicidins，被光解条件下，在三-的存在下完成Ñ使用谷氨酸-butyltin氢化物。这使得能够完成阿皮定A的总合成。
• Solid-phase synthesis of apicidin A and a cyclic tetrapeptoid analogue
  作者：Frédéric Berst、Mark Ladlow、Andrew B. Holmes

  DOI：10.1039/b110068h

  日期：——

  The solid-phase synthesis of the antiprotozoal cyclic tetrapeptide apicidin A is reported and its synthetic accessibility is contrasted with that of a structurally similar reduced cyclic tetrapeptoid analogue.

  报道了抗原生动物环状四肽阿皮菌素A的固相合成，其合成可及性与结构相似的还原性环状四肽类似物的可及性形成对比。
• Probing the elusive catalytic activity of vertebrate class IIa histone deacetylases
  作者：Philip Jones、Sergio Altamura、Raffaele De Francesco、Paola Gallinari、Armin Lahm、Petra Neddermann、Michael Rowley、Sergio Serafini、Christian Steinkühler

  DOI：10.1016/j.bmcl.2008.02.025

  日期：2008.3

  It has been widely debated whether class IIa HDACs have catalytic deacetylase activity, and whether this plays any part in controlling gene expression. Herein, it has been demonstrated that class IIa HDACs isolated from mammalian cells are contaminated with other deacetylases, but can be prepared cleanly in Escherichia coli. These bacteria preparations have weak but measurable deacetylase activity. The low efficiency can be restored either by: mutation of an active site histidine to tyrosine, or by the use of a non-acetylated lysine substrate, allowing the development of assays to identify class IIa HDAC inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.
• Synthesis of Apicidin-Derived Quinolone Derivatives:  Parasite-Selective Histone Deacetylase Inhibitors and Antiproliferative Agents
  作者：Peter T. Meinke、Steven L. Colletti、George Doss、Robert W. Myers、Anne M. Gurnett、Paula M. Dulski、Sandra J. Darkin-Rattray、John J. Allocco、Stefan Galuska、Dennis M. Schmatz、Matthew J. Wyvratt、Michael H. Fisher

  DOI：10.1021/jm0001976

  日期：2000.12.1

  Apicidin's indole was efficiently converted into a series of N-substituted quinolone derivatives by indole N-alkylation followed by a two-step, one-pot, ozonolysis/aldol condensation protocol. The new quinolones exhibited good parasite selectivity and potency both at the level of their molecular target, histone deacetylase, and in their whole cell antiproliferative activity in vitro.