dibenzyl (2S,3R)-2-benzyl-3-hydroxybutanedioate | 172275-56-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: dibenzyl (2S,3R)-2-benzyl-3-hydroxybutanedioate
• 英文别名: (2R,3S)-dibenzyl 2-benzyl-3-hydroxysuccinate；dibenzyl (2R,3S)-2-benzyl-3-hydroxysuccinate；dibenzyl (2R,3S)-2-benzyl-3-hydroxybutanedioate
• CAS: 172275-56-8
• 化学式: C₂₅H₂₄O₅
• 分子量: 404.463
• InChiKey: NCRKCELIGUCASZ-PKTZIBPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  dibenzyl (2S,3R)-2-benzyl-3-hydroxybutanedioate 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以56%的产率得到(2S,3S)-3-benzyl-1,2,4-butanetriol
  参考文献：
  名称：

  Stereospecific High-affinity TRPV1 Antagonists: Chiral N-(2-Benzyl-3-pivaloyloxypropyl) 2-[4-(methylsulfonylamino)phenyl]propionamide Analogues

  摘要：

  Previously, we reported the thiourea antagonists 2a and 2b as potent and high affinity TRPV1 antagonists. For further optimization of the lead compounds, a series of their amide and alpha-substituted amide surrogates were investigated and novel chiral N-(2-benzyl-3-pivaloyloxypropyl) 2-[4-(methylsulfonylamino)phenyl]propionamide analogues were characterized as potent and stereospecific rTRPV1 antagonists. In particular, compounds 72 and 73 displayed high binding affinities, with K-i values of 4.12 and 1.83 nM and potent antagonism with Ki values of 0.58 and 5.2 nM, respectively, in rTRPV1/CHO cells. These values are comparable or more potent than those of 5-iodoRTX under the same assay conditions. A distinctive binding model that includes two hydrophobic pockets is proposed for this series of compounds based on docking studies of 57 and 72 with a homology model of the TM3/4 region of TRPV1.

  DOI：

  10.1021/jm701049p
• 作为产物：
  描述：

  溴甲苯 、 dibenzyl L-malate 在 六甲基磷酰三胺 、 lithium hexamethyldisilazane 、 氯化铵 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.0h， 以54%的产率得到dibenzyl (2S,3R)-2-benzyl-3-hydroxybutanedioate
  参考文献：
  名称：

  A focus on the asymmetric synthesis of a novel threo-β-benzyl-β-hydroxy aspartate analogue

  摘要：

  Considering the biological activity of beta-alkyl-beta-hydroxyaspartate derivatives as potent blockers of glutamate transporters (EAATs) impacting on glutamatergic synapses activity, we have developed a concise, asymmetric synthesis of enantiomerically pure threo-beta-benzyl-beta-hydroxyaspartates. The key step is a regiospecific and stereoselective Sharpless asymmetric aminohydroxylation (SAA) on previously synthesized benzyl fumarate. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2012.01.004

文献信息

• (2R, 3S)- and (2S, 3R)-2-Benzyl-3,4-epoxybutanoic acid as highly efficient and fast acting pseudomechanism-based inactivators for carboxypeptidase a: design, asymmetric synthesis and inhibitory kinetics
  作者：Soo Suk Lee、Zhi-Hong Li、Dong Ha Lee、Dong H. Kim

  DOI：10.1039/p19950002877

  日期：——

  2-Benzyl-3,4-epoxybutanoic acid (BEBA) was studied as an irreversible inhibitor for the zinc-containing protease, carboxypeptidase A. Of four possible stereoisomers, those having a 2R,3S- and a 2S,3R-configuration inhibited carboxypeptidase A in a time dependent manner. The latter compound that belongs to the D series is more effective with a k(inact)/K-i value of 139.5 dm(3) mol(-1) s(-1) than the former having a K-inact/K-i value of 53.9 dm(3) mol(-1) s(-1). Partition ratios, fore (2R,3S)- and (2S,3R)-BEBA were determined as 1.01 and 0.53, respectively. The observed kinetic parameters reveal that both are highly efficient and fast acting pseudomechanism-based inactivators for carboxypeptidase A. Details of the kinetic analyses, design principles and asymmetric syntheses of these inactivators are described.
• Stereospecific High-affinity TRPV1 Antagonists: Chiral <i>N</i>-(2-Benzyl-3-pivaloyloxypropyl) 2-[4-(methylsulfonylamino)phenyl]propionamide Analogues
  作者：HyungChul Ryu、Mi-Kyoung Jin、Su Yeon Kim、Hyun-Kyung Choi、Sang-Uk Kang、Dong Wook Kang、Jeewoo Lee、Larry V. Pearce、Vladimir A. Pavlyukovets、Matthew A. Morgan、Richard Tran、Attila Toth、Daniel J. Lundberg、Peter M. Blumberg

  DOI：10.1021/jm701049p

  日期：2008.1.1

  Previously, we reported the thiourea antagonists 2a and 2b as potent and high affinity TRPV1 antagonists. For further optimization of the lead compounds, a series of their amide and alpha-substituted amide surrogates were investigated and novel chiral N-(2-benzyl-3-pivaloyloxypropyl) 2-[4-(methylsulfonylamino)phenyl]propionamide analogues were characterized as potent and stereospecific rTRPV1 antagonists. In particular, compounds 72 and 73 displayed high binding affinities, with K-i values of 4.12 and 1.83 nM and potent antagonism with Ki values of 0.58 and 5.2 nM, respectively, in rTRPV1/CHO cells. These values are comparable or more potent than those of 5-iodoRTX under the same assay conditions. A distinctive binding model that includes two hydrophobic pockets is proposed for this series of compounds based on docking studies of 57 and 72 with a homology model of the TM3/4 region of TRPV1.
• A focus on the asymmetric synthesis of a novel threo-β-benzyl-β-hydroxy aspartate analogue
  作者：Sofiane Mekki、Salima Bellahouel、Nicolas Vanthuyne、Marc Rolland、Aicha Derdour、Jean Martinez、Michel Vignes、Valérie Rolland

  DOI：10.1016/j.tetasy.2012.01.004

  日期：2012.1

  Considering the biological activity of beta-alkyl-beta-hydroxyaspartate derivatives as potent blockers of glutamate transporters (EAATs) impacting on glutamatergic synapses activity, we have developed a concise, asymmetric synthesis of enantiomerically pure threo-beta-benzyl-beta-hydroxyaspartates. The key step is a regiospecific and stereoselective Sharpless asymmetric aminohydroxylation (SAA) on previously synthesized benzyl fumarate. (C) 2012 Elsevier Ltd. All rights reserved.