(S)-2-(dibenzylamino)-6-oxohexanoic acid benzyl ester | 874384-02-8

• 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: (S)-2-(dibenzylamino)-6-oxohexanoic acid benzyl ester
• 英文别名: (S)-2-dibenzylamino-6-oxohexanoic acid benzyl ester；benzyl (S)-2-(dibenzylamino)-6-oxohexanoate；benzyl (2S)-2-(dibenzylamino)-6-oxohexanoate
• CAS: 874384-02-8
• 化学式: C₂₇H₂₉NO₃
• 分子量: 415.532
• InChiKey: WVSLAWHFTHUVJY-SANMLTNESA-N

物化性质

• 沸点：
  541.7±50.0 °C(Predicted)
• 密度：
  1.130±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  31
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-2-(dibenzylamino)-6-oxohexanoic acid benzyl ester 在 palladium dihydroxide 氢气 、 N,N-二异丙基乙胺 、 lithium chloride 作用下， 以 甲醇 、 乙腈 为溶剂， 20.0 ℃ 、607.95 kPa 条件下， 反应 84.0h， 生成 (2S)-2-氨基-8-氧代癸酸
  参考文献：
  名称：

  Synthesis of 2-Amino-8-oxodecanoic Acids (Aodas) Present in Natural Hystone Deacetylase Inhibitors

  摘要：

  Differently substituted 2-amino-8-oxodecanoic acids (Aodas), present in naturally occurring inhibitors of hystone deacetylase (HDAC), have been prepared using a convergent approach. The configuration in position 2 was derived from enantiomerically pure allylglycine or glutamic acid, whereas the stereochemistry of the substituent in position 9 derived from lactic acid or glyceraldehyde derivatives. Starting from allylglycine, (S)-Aodas, protected at the nitrogen as Boc or Fmoc, were obtained in four steps in about 30% overall yield. These products have been used to prepare a simplified analogue of a natural cyclic tetrapeptide HDAC inhibitor by SPPS.

  DOI：

  10.1021/jo0518250
• 作为产物：
  描述：

  (S)-(-)-2-氨基-4-戊烯酸 在 dicarbonylacetylacetonato rhodium (I) 、 (R,R,R)-BOBPHOS 、 氢气 、 sodium carbonate 、 sodium hydroxide 作用下， 以 水 、 甲苯 为溶剂， 25.0~50.0 ℃ 、500.01 kPa 条件下， 反应 18.0h， 生成 (S)-2-(dibenzylamino)-6-oxohexanoic acid benzyl ester
  参考文献：
  名称：

  非对映选择性和支链醛选择性串联加氢甲酰化-半缩醛形成：官能化哌啶和氨基醇的合成

  摘要：

  从容易获得的烯丙基甘氨酸开始，已开发出串联加氢甲酰化-半胱氨酸形成反应，用于合成手性官能化哌啶，使用Rh /（S，S，S）-BOBPHOS催化剂具有非常好的非对映选择性和支链区域选择性。串联加氢甲酰化-半缩醛的形成也具有良好的非对映选择性（88:12），半缩醛产物被氢化并保留了立体化学，从而提供了一种手性中间体，用于合成新的抗生素奈诺沙星。

  DOI：

  10.1021/acs.orglett.7b01049

文献信息

• Lactam based 7-amino suberoylamide hydroxamic acids as potent HDAC inhibitors
  作者：Maurizio Taddei、Elena Cini、Luca Giannotti、Giuseppe Giannini、Gianfranco Battistuzzi、Davide Vignola、Loredana Vesci、Walter Cabri

  DOI：10.1016/j.bmcl.2013.11.072

  日期：2014.1

  A series of SAHA-like molecules were prepared introducing different lactam-carboxyamides in position 7 of the suberoylanilide skeleton. The activity against different HDAC isoforms was tested and the data compared with the corresponding linear products, without substituent in position 7. In general, this modification provided an effective reinforcement of in vitro activity. While the lactam size or the CO/NH group orientation did not strongly influence the inhibition, the contemporary modification of the suberoylamide fragment gave vary active variants in the lactam series, with compound 28 (ST8078AA1) that showed IC50 values between 2 and 10 nM against all Class I HDAC isoforms, demonstrating it to be a large spectrum pan-inhibitor. This strong affinity with HDAC was also confirmed by the value of IC50 = 0.5 mu M against H460 cells, ranking 28 as one of the most potent HDAC inhibitors described so far. (C) 2013 Elsevier Ltd. All rights reserved.
• Total Synthesis, NMR Solution Structure, and Binding Model of the Potent Histone Deacetylase Inhibitor FR235222
  作者：Manuela Rodriquez、Stefania Terracciano、Elena Cini、Giulia Settembrini、Ines Bruno、Giuseppe Bifulco、Maurizio Taddei、Luigi Gomez-Paloma

  DOI：10.1002/anie.200501995

  日期：2006.1.9
• Synthesis of 2-Amino-8-oxodecanoic Acids (Aodas) Present in Natural Hystone Deacetylase Inhibitors
  作者：Manuela Rodriquez、Ines Bruno、Elena Cini、Mauro Marchetti、Maurizio Taddei、Luigi Gomez-Paloma

  DOI：10.1021/jo0518250

  日期：2006.1.1

  Differently substituted 2-amino-8-oxodecanoic acids (Aodas), present in naturally occurring inhibitors of hystone deacetylase (HDAC), have been prepared using a convergent approach. The configuration in position 2 was derived from enantiomerically pure allylglycine or glutamic acid, whereas the stereochemistry of the substituent in position 9 derived from lactic acid or glyceraldehyde derivatives. Starting from allylglycine, (S)-Aodas, protected at the nitrogen as Boc or Fmoc, were obtained in four steps in about 30% overall yield. These products have been used to prepare a simplified analogue of a natural cyclic tetrapeptide HDAC inhibitor by SPPS.
• Diastereoselective and Branched-Aldehyde-Selective Tandem Hydroformylation–Hemiaminal Formation: Synthesis of Functionalized Piperidines and Amino Alcohols
  作者：Rachael Pittaway、José A. Fuentes、Matthew L. Clarke

  DOI：10.1021/acs.orglett.7b01049

  日期：2017.6.2

  developed for the synthesis of chiral functionalized piperidines, with very good diastereoselectivity and branched regioselectivity using Rh/(S,S,S)-BOBPHOS catalysts. Tandem hydroformylation–hemiacetal formation also proceeds with good diastereoselectivity (88:12), with the hemiacetal product being hydrogenated with retention of stereochemistry to give a chiral intermediate used in the synthesis of the new

  从容易获得的烯丙基甘氨酸开始，已开发出串联加氢甲酰化-半胱氨酸形成反应，用于合成手性官能化哌啶，使用Rh /（S，S，S）-BOBPHOS催化剂具有非常好的非对映选择性和支链区域选择性。串联加氢甲酰化-半缩醛的形成也具有良好的非对映选择性（88:12），半缩醛产物被氢化并保留了立体化学，从而提供了一种手性中间体，用于合成新的抗生素奈诺沙星。