(1S,2R,6R)-2-Benzyloxycarbonylamino-6-methylcyclohexane-1-carboxylic acid methyl ester | 213838-14-3

• 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: (1S,2R,6R)-2-Benzyloxycarbonylamino-6-methylcyclohexane-1-carboxylic acid methyl ester
• 英文别名: methyl (1S,2R,6R)-2-methyl-6-(phenylmethoxycarbonylamino)cyclohexane-1-carboxylate
• CAS: 213838-14-3
• 化学式: C₁₇H₂₃NO₄
• 分子量: 305.374
• InChiKey: NGNCDUKWOPUGHM-YUELXQCFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 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：

  (1S,2R,6R)-2-Benzyloxycarbonylamino-6-methylcyclohexane-1-carboxylic acid methyl ester 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 甲酸 、 乙醇 为溶剂， 反应 19.0h， 生成 methyl (1S,2R,6R)-2-methyl-6-[[(Z)-1-(4-methylphenyl)sulfonylpent-1-en-2-yl]amino]cyclohexane-1-carboxylate
  参考文献：
  名称：

  Enantioselective Synthesis of (−)-Pumiliotoxin C from a Chiral Amino Ester and an Acetylenic Sulfone that Acts as an Alkene Dipole Equivalent

  摘要：

  A new synthesis of the naturally occurring (-)-enantiomer of the dendrobatid alkaloid pumiliotoxin C (1) was achieved by the conjugate addition of methyl (-)-cis-2-amino-trans-6-methylcyclohexanecarboxylate (3) to 1-(p-toluenesulfonyl)-1-pentyne (4), followed by intramolecular acylation to afford (4aS,5R,8aR)-4a,5,6,7,8,8a-hexahydro-5-methyl-2-propyl-3-(p-toluenesulfonyl)-4-quinolinone (2). The acetylenic sulfone thus acts as the synthetic equivalent of an alkene dipole species. The required enantiopure amino ester 3 was obtained by an approach based on pig liver esterase (PLE)-mediated hydrolysis. Thus, the (-)- and (+)-enantiomers of racemic dimethyl trans-3-methylcyclohexane-cis,cis-1,2-dicarboxylate (6) afforded the corresponding half-esters 7 and 8, respectively, when treated with PLE. The desired half-ester 7 was recovered intact after selective conversion of the free carboxylic acid group of the byproduct 8 into its benzyl ester. Half-ester 7 was converted into enantiopure (-)-6 with diazomethane, followed by regioselective saponification and Curtius rearrangement to afford the required enantiopure key intermediate 3. Finally, hydrogenation of the enol triflate of enaminone 2, followed by reductive desulfonylation, afforded the product (-)-1.

  DOI：

  10.1021/jo980647q
• 作为产物：
  描述：

  (1S,2R,6R)-2-methoxycarbonyl-6-methylcyclohexane-1-carboxylic acid 以 乙醚 为溶剂， 生成 (1S,2R,6R)-2-Benzyloxycarbonylamino-6-methylcyclohexane-1-carboxylic acid methyl ester
  参考文献：
  名称：

  Enantioselective Synthesis of (−)-Pumiliotoxin C from a Chiral Amino Ester and an Acetylenic Sulfone that Acts as an Alkene Dipole Equivalent

  摘要：

  A new synthesis of the naturally occurring (-)-enantiomer of the dendrobatid alkaloid pumiliotoxin C (1) was achieved by the conjugate addition of methyl (-)-cis-2-amino-trans-6-methylcyclohexanecarboxylate (3) to 1-(p-toluenesulfonyl)-1-pentyne (4), followed by intramolecular acylation to afford (4aS,5R,8aR)-4a,5,6,7,8,8a-hexahydro-5-methyl-2-propyl-3-(p-toluenesulfonyl)-4-quinolinone (2). The acetylenic sulfone thus acts as the synthetic equivalent of an alkene dipole species. The required enantiopure amino ester 3 was obtained by an approach based on pig liver esterase (PLE)-mediated hydrolysis. Thus, the (-)- and (+)-enantiomers of racemic dimethyl trans-3-methylcyclohexane-cis,cis-1,2-dicarboxylate (6) afforded the corresponding half-esters 7 and 8, respectively, when treated with PLE. The desired half-ester 7 was recovered intact after selective conversion of the free carboxylic acid group of the byproduct 8 into its benzyl ester. Half-ester 7 was converted into enantiopure (-)-6 with diazomethane, followed by regioselective saponification and Curtius rearrangement to afford the required enantiopure key intermediate 3. Finally, hydrogenation of the enol triflate of enaminone 2, followed by reductive desulfonylation, afforded the product (-)-1.

  DOI：

  10.1021/jo980647q

文献信息

• Efficient Asymmetric Synthesis of Unnatural β-Amino Acids
  作者：Carsten Bolm、Ingo Schiffers、Christian L. Dinter、Laurent Defrère、Arne Gerlach、Gerhard Raabe

  DOI：10.1055/s-2001-16745

  日期：——

  The simple and highly enantioselective methanolysis of cyclic meso-anhydrides mediated by cinchona alkaloids leads to a broad variety of dicarboxylic acid mono-methyl esters with up to 99% ee. From these products, unnatural N-protected β-amino esters can be obtained by means of Curtius degradation of the corresponding acyl azides. Subsequent cleavage of the protecting groups leads to the free β-amino acids in excellent yields. By enantiomer differentiating opening of racemic anhydrides, synthetically highly useful regioisomeric amino acid esters become readily available.

  由金鸡纳生物碱介导的环状内消旋酸酐的简单且高度对映选择性的甲醇分解可产生多种二羧酸单甲酯，其 ee 高达 99%。从这些产品中，可以通过 Curtius 降解相应的酰基叠氮获得非天然的 N-保护的 β-氨基酯。随后保护基团的裂解导致游离β-氨基酸的产率极好。通过外消旋酸酐的对映异构体差异化打开，合成上非常有用的区域异构氨基酸酯变得容易获得。
• Enantioselective Synthesis of (−)-Pumiliotoxin C from a Chiral Amino Ester and an Acetylenic Sulfone that Acts as an Alkene Dipole Equivalent
  作者：Thomas G. Back、Katsumasa Nakajima

  DOI：10.1021/jo980647q

  日期：1998.9.1

  A new synthesis of the naturally occurring (-)-enantiomer of the dendrobatid alkaloid pumiliotoxin C (1) was achieved by the conjugate addition of methyl (-)-cis-2-amino-trans-6-methylcyclohexanecarboxylate (3) to 1-(p-toluenesulfonyl)-1-pentyne (4), followed by intramolecular acylation to afford (4aS,5R,8aR)-4a,5,6,7,8,8a-hexahydro-5-methyl-2-propyl-3-(p-toluenesulfonyl)-4-quinolinone (2). The acetylenic sulfone thus acts as the synthetic equivalent of an alkene dipole species. The required enantiopure amino ester 3 was obtained by an approach based on pig liver esterase (PLE)-mediated hydrolysis. Thus, the (-)- and (+)-enantiomers of racemic dimethyl trans-3-methylcyclohexane-cis,cis-1,2-dicarboxylate (6) afforded the corresponding half-esters 7 and 8, respectively, when treated with PLE. The desired half-ester 7 was recovered intact after selective conversion of the free carboxylic acid group of the byproduct 8 into its benzyl ester. Half-ester 7 was converted into enantiopure (-)-6 with diazomethane, followed by regioselective saponification and Curtius rearrangement to afford the required enantiopure key intermediate 3. Finally, hydrogenation of the enol triflate of enaminone 2, followed by reductive desulfonylation, afforded the product (-)-1.