(4S,5R)-4-环己基甲基-2-恶唑烷酮-5-羧酸甲酯 | 134848-78-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 中文名称: (4S,5R)-4-环己基甲基-2-恶唑烷酮-5-羧酸甲酯
• 英文名称: methyl (4S,5R)-4-(cyclohexylmethyl)-2-oxo-5-oxazolidinecarboxylate
• 英文别名: (4S,5R)-4-cyclohexylmethyl-2-oxazolidinone-5-carboxylic acid methyl ester；methyl (4S,5R)-4-cyclohexylmethyl-2-oxo-oxazolidine-5-carboxylate；methyl (4S,5R)-4-(cyclohexylmethyl)-2-oxo-1,3-oxazolidine-5-carboxylate
• CAS: 134848-78-5
• 化学式: C₁₂H₁₉NO₄
• 分子量: 241.287
• InChiKey: QNXTZJCHVLHPAZ-VHSXEESVSA-N

物化性质

• 沸点：
  423.1±34.0 °C(Predicted)
• 密度：
  1.149±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4S,5R)-4-环己基甲基-2-恶唑烷酮-5-羧酸甲酯 在 三甲基铝 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 26.5h， 生成 (4S,5R)-5-(2-but-3-enyl-1,3-dioxolan-2-yl)-4-(cyclohexylmethyl)-1,3-oxazolidin-2-one
  参考文献：
  名称：

  Design and synthesis of P2-P1'-linked macrocyclic human renin inhibitors

  摘要：

  Using a computer model of the active site of human renin developed at Merck, we designed a series of novel P2-P1'-linked, macrocyclic renin inhibitors 3-10. These unique inhibitors incorporate a transition-state isostere within a 13- or 14-membered ring. The three most active compounds in this family were 13-membered-ring glutamine-derived inhibitor 3, 14-membered-ring diaminopropionic acid derived inhibitor 6, and 13-membered-ring diol 9 (IC50 0.61, 0.59, 0.65-mu-M, respectively). Modification of inhibitor 3 at P4 led to 56 nM macrocyclic renin inhibitor 39. This study shows the viability of renin inhibitor designs which incorporate a scissile-bond replacement within a macrocycle.

  DOI：

  10.1021/jm00113a005
• 作为产物：
  描述：

  ethyl 4-cyclohexyl-2-oxo-butyrate 在 palladium on activated charcoal sodium hydroxide 、 {bis[(4R,5S)-di-Ph-oxazoline-2-yl]methane}Cu(OTf)2 、 氢气 、 L-Selectride 、 溶剂黄146 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 丙酮 、 甲苯 为溶剂， 反应 19.25h， 生成 (4S,5R)-4-环己基甲基-2-恶唑烷酮-5-羧酸甲酯
  参考文献：
  名称：

  Catalytic Asymmetric Direct α-Amination Reactions of 2-Keto Esters:  A Simple Synthetic Approach to Optically Active syn-β-Amino-α-hydroxy Esters

  摘要：

  The catalytic enantioselective direct alpha-amination reaction of 2-keto esters with easily available azo dicarboxylates as the nitrogen source and chiral bisoxazoline-copper(II) complexes as the catalyst is presented. The reactions proceed with excellent enantioselectivities and high yields. The scope of the reaction is demonstrated by the direct amination of a series of 2-keto esters having different substituent patterns. The reaction provides an easy catalytic route to optically active syn-beta-amino-alpha-hydroxy esters, as demonstrated for the synthesis of masked syn-beta-amino-alpha-hydroxy esters (as oxazolidinones) and N-Boc-syn-beta-amino-alpha-hydroxy esters. On the basis of the absolute configuration of the products a tentative model for the transition state is suggested.

  DOI：

  10.1021/ja0175486

文献信息

• Process for the manufacture of (4,5)-trans-oxazolidines
  申请人：Hoffmann-La Roche Inc.

  公开号：US05670653A1

  公开（公告）日：1997-09-23

  Compounds containing a (4,5)-cis-2-oxo-oxazolidine ring are isomerized to the corresponding (4,5)-trans-2-oxo-oxazolidine by treating the cis compound with a strong base.

  含有(4,5)-顺式-2-氧代噁唑啉环的化合物可以通过使用强碱处理顺式化合物，使其异构化为相应的(4,5)-反式-2-氧代噁唑啉。
• Design and synthesis of P2-P1'-linked macrocyclic human renin inhibitors
  作者：Ann E. Weber、Thomas A. Halgren、John J. Doyle、Robert J. Lynch、Peter K. S. Siegl、William H. Parsons、William J. Greenlee、Arthur A. Patchett

  DOI：10.1021/jm00113a005

  日期：1991.9

  Using a computer model of the active site of human renin developed at Merck, we designed a series of novel P2-P1'-linked, macrocyclic renin inhibitors 3-10. These unique inhibitors incorporate a transition-state isostere within a 13- or 14-membered ring. The three most active compounds in this family were 13-membered-ring glutamine-derived inhibitor 3, 14-membered-ring diaminopropionic acid derived inhibitor 6, and 13-membered-ring diol 9 (IC50 0.61, 0.59, 0.65-mu-M, respectively). Modification of inhibitor 3 at P4 led to 56 nM macrocyclic renin inhibitor 39. This study shows the viability of renin inhibitor designs which incorporate a scissile-bond replacement within a macrocycle.
• Catalytic Asymmetric Direct α-Amination Reactions of 2-Keto Esters:  A Simple Synthetic Approach to Optically Active <i>syn</i>-β-Amino-α-hydroxy Esters
  作者：Karsten Juhl、Karl Anker Jørgensen

  DOI：10.1021/ja0175486

  日期：2002.3.1

  The catalytic enantioselective direct alpha-amination reaction of 2-keto esters with easily available azo dicarboxylates as the nitrogen source and chiral bisoxazoline-copper(II) complexes as the catalyst is presented. The reactions proceed with excellent enantioselectivities and high yields. The scope of the reaction is demonstrated by the direct amination of a series of 2-keto esters having different substituent patterns. The reaction provides an easy catalytic route to optically active syn-beta-amino-alpha-hydroxy esters, as demonstrated for the synthesis of masked syn-beta-amino-alpha-hydroxy esters (as oxazolidinones) and N-Boc-syn-beta-amino-alpha-hydroxy esters. On the basis of the absolute configuration of the products a tentative model for the transition state is suggested.