bis(ethoxycarbonylmethyl) 1,4-dihydro-2,6-dimethyl-4-(3'-nitrophenyl)pyridine-3,5-dicarboxylate | 152253-22-0

• 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: bis(ethoxycarbonylmethyl) 1,4-dihydro-2,6-dimethyl-4-(3'-nitrophenyl)pyridine-3,5-dicarboxylate
• 英文别名: Bis(2-ethoxy-2-oxoethyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate；bis(2-ethoxy-2-oxoethyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 152253-22-0
• 化学式: C₂₃H₂₆N₂O₁₀
• 分子量: 490.467
• InChiKey: OXKHAGBQWKCNKN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  35
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  163
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  bis(ethoxycarbonylmethyl) 1,4-dihydro-2,6-dimethyl-4-(3'-nitrophenyl)pyridine-3,5-dicarboxylate 在 Novozym 435 、 potassium carbonate 作用下， 以 phosphate buffer 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 22.0h， 生成 ethoxycarbonylmethyl methoxycarbonylmethyl 1,4-dihydro-2,6-dimethyl-4-(3'-nitrophenyl)-pyridine-3,5-dicarboxylate
  参考文献：
  名称：

  Candida antarctica lipase-catalyzed hydrolysis of 4-substituted bis(ethoxycarbonylmethyl) 1,4-dihydropyridine-3,5-dicarboxylates as the key step in the synthesis of optically active dihydropyridines

  摘要：

  Prochiral bis(ethoxycarbonylmethyl) substituted 4-aryl-1,4-dihydropyridine-3,5-dicarboxylates were hydrolyzed enantioselectively by Candida antarctica lipase B (Novozym 435). The enantiomeric excesses varied from 68 to 93%, depending on the substituent at position 4. In some cases, the e.e. could be significantly increased by changing the solvent system. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(00)00441-9
• 作为产物：
  描述：

  间硝基苯甲醛 、 ethoxycarbonylmethyl acetoacetate 在 ammonium hydroxide 作用下， 以 乙醇 为溶剂， 反应 6.0h， 以67%的产率得到bis(ethoxycarbonylmethyl) 1,4-dihydro-2,6-dimethyl-4-(3'-nitrophenyl)pyridine-3,5-dicarboxylate
  参考文献：
  名称：

  Candida antarctica lipase-catalyzed hydrolysis of 4-substituted bis(ethoxycarbonylmethyl) 1,4-dihydropyridine-3,5-dicarboxylates as the key step in the synthesis of optically active dihydropyridines

  摘要：

  Prochiral bis(ethoxycarbonylmethyl) substituted 4-aryl-1,4-dihydropyridine-3,5-dicarboxylates were hydrolyzed enantioselectively by Candida antarctica lipase B (Novozym 435). The enantiomeric excesses varied from 68 to 93%, depending on the substituent at position 4. In some cases, the e.e. could be significantly increased by changing the solvent system. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(00)00441-9

文献信息

• Protease-catalyzed enantioselective synthesis of optically active 14-dihydropyridines
  作者：Yoshihiko Hirose、Kinya Kariya、Ikuharu Sasaki、Yoshiaki Kurono、Kazuo Achiwa

  DOI：10.1016/s0040-4039(00)79178-7

  日期：1993.5

  The first enantioselective protease-catalyzed hydrolyses of 1,4-dihydropyridine-3,5-dicarboxyric diesters were developed. The monoesters obtained had high optical purity and were useful chiral building blocks which could easily lead to optically active Cablockers.

  开发了1,4-二氢吡啶-3,5-二羧基二酯的第一个对映选择性蛋白酶催化的水解物。所获得的单酯具有高的光学纯度，并且是有用的手性结构单元，其可以容易地产生光学活性的Cablockers。
• Carbamoylmethyl group as an activated group in protease- and base-catalyzed transesterification of 1,4-dihydropyridines: A novel asymmetric synthesis of valnidipine
  作者：Yoshihiko Hirose、Kinya Kariya、Ikuharu Sasaki、Yoshiaki Kurono、Kazuo Achiwa

  DOI：10.1016/s0040-4039(00)73813-5

  日期：1993.9

  The first protease-catalyzed enantioselective transesterification of 1,4-dihydropyridine-3,5-dicarboxylates in an aqueous solution was developed with high optical purity. Carbamoylmethyl ester group was enantioselectively transesterificated with (S)-N-benzyl-3-pyrroridinol by the protease and successive base-catalyzed transesterification proceeded smoothly to give the chiral drug, valnidipine, in a good yield.
• Inversion of enantioselectivity in hydrolysis of 1,4-dihydropyridines by point mutation of lipase PS
  作者：Yoshihiko Hirose、Kinya Kariya、Yuji Nakanishi、Yoshiaki Kurono、Kazuo Achiwa

  DOI：10.1016/0040-4039(94)02454-j

  日期：1995.2

  Mutant of lipase PS replaced three amino acids by site-specific mutagenesis first showed the inversion of enantioselectivity and the solvent effect in hydrolysis of 1,4-dihydropyridines.