(R)-4-benzyl-3-((R)-2,3-dimethylbutanoyl)oxazolidin-2-one | 1432629-51-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (R)-4-benzyl-3-((R)-2,3-dimethylbutanoyl)oxazolidin-2-one
• 英文别名: (4R)-4-benzyl-3-[(2R)-2,3-dimethylbutanoyl]-1,3-oxazolidin-2-one
• CAS: 1432629-51-0
• 化学式: C₁₆H₂₁NO₃
• 分子量: 275.348
• InChiKey: RSUPKDAKMUHKTO-TZMCWYRMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  (R)-3-(3-甲基丁酰)-4-苄基-2-恶唑烷酮	(R)-4-benzyl-3-(3-methylbutyryl)oxazolidin-2-one	145589-03-3	C15H19NO3	261.321

反应信息

• 作为反应物：
  描述：

  (R)-4-benzyl-3-((R)-2,3-dimethylbutanoyl)oxazolidin-2-one 在 双氧水 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 6.0h， 以81%的产率得到(R)-2,3-二甲基丁酸
  参考文献：
  名称：

  高效的（2R，3R，4R）-2-氨基-3-羟基-4,5-二甲基己酸（高草甘膦A的内酯连接单元）的非对映选择性合成。

  摘要：

  为了完全合成新型环二肽高草胺A，成功地通过Evans的不对称烷基化和手性化合物的抗选择性不对称氢化成功合成了（2R，3R，4R）-2-氨基-3-羟基-4,5-二甲基己酸α-氨基-β-酮酸酯为关键步骤。

  DOI：

  10.1248/cpb.c12-00944
• 作为产物：
  描述：

  异戊酰氯 在 正丁基锂 、 二异丙胺 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 8.5h， 生成 (R)-4-benzyl-3-((R)-2,3-dimethylbutanoyl)oxazolidin-2-one
  参考文献：
  名称：

  Rational Design of Thermodynamic and Kinetic Binding Profiles by Optimizing Surface Water Networks Coating Protein-Bound Ligands

  摘要：

  A previously studied congeneric series of thermolysin inhibitors addressing the solvent-accessible S-2' pocket with different hydrophobic substituents showed modulations of the surface water layers coating the protein-bound inhibitors. Increasing stabilization of water molecules resulted in an enthalpically more favorable binding signature, overall enhancing affinity. Based on this observation, we optimized the series by designing tailored P-2' substituents to improve and further stabilize the surface water network. MD simulations were applied to predict the putative water pattern around the bound ligands. Subsequently, the inhibitors were synthesized and characterized by high-resolution crystallography, microcalorimetry, and surface plasmon resonance. One of the designed inhibitors established the most pronounced water network of all inhibitors tested so far, composed of several fused water polygons, and showed 50-fold affinity enhancement with respect to the original methylated parent ligand. Notably, the inhibitor forming the most perfect water network also showed significantly prolonged residence time compared to the other tested inhibitors.

  DOI：

  10.1021/acs.jmedchem.6b00998

文献信息

• Efficient Diastereoselective Synthesis of (2<i>R</i>,3<i>R</i>,4<i>R</i>)-2-Amino-3-hydroxy-4,5-dimethylhexanoic Acid, the Lactone Linkage Unit of Homophymine A
  作者：Junpei Ohtaka、Akinari Hamajima、Tetsuhiro Nemoto、Yasumasa Hamada

  DOI：10.1248/cpb.c12-00944

  日期：——

  For the total synthesis of novel cyclodepsipeptide homophymine A, (2R,3R,4R)-2-amino-3-hydroxy-4,5-dimethylhexanoic acid was successfully synthesized by Evans' asymmetric alkylation and the anti-selective asymmetric hydrogenation of a chiral α-amino-β-keto ester as the key steps.

  为了完全合成新型环二肽高草胺A，成功地通过Evans的不对称烷基化和手性化合物的抗选择性不对称氢化成功合成了（2R，3R，4R）-2-氨基-3-羟基-4,5-二甲基己酸α-氨基-β-酮酸酯为关键步骤。
• Rational Design of Thermodynamic and Kinetic Binding Profiles by Optimizing Surface Water Networks Coating Protein-Bound Ligands
  作者：Stefan G. Krimmer、Jonathan Cramer、Michael Betz、Veronica Fridh、Robert Karlsson、Andreas Heine、Gerhard Klebe

  DOI：10.1021/acs.jmedchem.6b00998

  日期：2016.12.8

  A previously studied congeneric series of thermolysin inhibitors addressing the solvent-accessible S-2' pocket with different hydrophobic substituents showed modulations of the surface water layers coating the protein-bound inhibitors. Increasing stabilization of water molecules resulted in an enthalpically more favorable binding signature, overall enhancing affinity. Based on this observation, we optimized the series by designing tailored P-2' substituents to improve and further stabilize the surface water network. MD simulations were applied to predict the putative water pattern around the bound ligands. Subsequently, the inhibitors were synthesized and characterized by high-resolution crystallography, microcalorimetry, and surface plasmon resonance. One of the designed inhibitors established the most pronounced water network of all inhibitors tested so far, composed of several fused water polygons, and showed 50-fold affinity enhancement with respect to the original methylated parent ligand. Notably, the inhibitor forming the most perfect water network also showed significantly prolonged residence time compared to the other tested inhibitors.