methyl 4-aza-4-(tert-butoxycarbonyl)-8-oxooctanoate | 170513-49-2

• 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: methyl 4-aza-4-(tert-butoxycarbonyl)-8-oxooctanoate
• 英文别名: Methyl 3-[(2-methylpropan-2-yl)oxycarbonyl-(4-oxobutyl)amino]propanoate
• CAS: 170513-49-2
• 化学式: C₁₃H₂₃NO₅
• 分子量: 273.329
• InChiKey: RFOZILZRZSBCQM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  19
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 4-aza-4-(tert-butoxycarbonyl)-8-oxooctanoate 在 哌啶 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 17.5h， 生成 (E)-methyl 4-aza-4-(tert-butoxycarbonyl)-7-(ethoxymethoxy)-9-(phenylsulfonyl)non-8-enoate
  参考文献：
  名称：

  Stereoselective Synthesis of Polyhydroxylated Indolizidines from γ-Hydroxy α,β-Unsaturated Sulfones

  摘要：

  The polyhydroxylated indolizidines castanospermine and swainsonine as well as some of their stereoisomers are powerful glycosidase inhibitors. An efficient and stereochemically flexible synthesis of racemic 1,7,8-trihydroxylated and 1,6,7,8-tetrahydroxylated indolizidines (castanospermine stereoisomers) from readily available N-substituted gamma-oxygenated alpha,beta-unsaturated sulfones 3 and 4 has been developed. The construction of the bicyclic skeleton of 1-hydroxyindolizidine has been accomplished by intramolecular conjugate addition of the nitrogen moiety of 3 and 4 to the alpha,beta-unsaturated sulfone unit to give the pyrrolidine intermediates 5 and 6, followed by formation of the C(7)-C(8) bond by intramolecular acylation (or alkylation) of the alpha-sulfonyl carbanion. The stereoselectivity of the pyrrolidine synthesis was highly dependent on the bulkiness of the gamma-oxygenated function; thus, the free alcohols gave predominantly cis-pyrrolidines while the OTIPS derivatives led to the trans isomers. After straightforward functional group transformations, the removal of the sulfonyl group at C(8) either by Julia reaction or by basic elimination (depending on the substrate used) afforded the key C(7)C(8) unsaturated indolizidines 10, 22, 30, and 31, whose stereoselective dihydroxylations with OsO4 gave a variety of cis C(1)C(8a) and-trans C(1)C(8a) trihydroxylated and tetrahydroxylated indolizidines, among which (+/-)-1,7-di-epi-castanospermine and (+/-)-1,8-di-epi-castanospermine have been reported for the first time.

  DOI：

  10.1021/jo972167p
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 0.33h， 生成 methyl 4-aza-4-(tert-butoxycarbonyl)-8-oxooctanoate
  参考文献：
  名称：

  通过γ-氧化的α，β-不饱和砜环化的立体选择性合成羟基吡咯烷和羟基哌啶

  摘要：

  顺式和反式2，3-二取代的吡咯烷和哌啶已通过分子内共轭添加N-取代的γ-氧化的-α，β-不饱和苯基砜而立体制备。从醇获得最佳的顺式选择性，从OTIPS衍生物获得最佳的反式选择性。

  DOI：

  10.1016/0040-4039(96)00551-5

文献信息

• Efficient Synthesis of Indolizidine Alkaloids from γ-Hydroxy-α,β-unsaturated Sulfones
  作者：Juan C. Carretero、Ramon Gomez Arrayas、Isabel Storch De Gracia、Javier Adrio

  DOI：10.1080/10426509708545542

  日期：1997.1.1
• Efficient stereoselective access to polyhydroxylated indolizidine compounds based on .gamma.-hydroxy-.alpha.,.beta.-unsaturated sulfones
  作者：Juan C. Carretero、Ramon Gomez Arrayas

  DOI：10.1021/jo00124a002

  日期：1995.9
• Stereoselective Synthesis of Polyhydroxylated Indolizidines from γ-Hydroxy α,β-Unsaturated Sulfones
  作者：Juan C. Carretero、Ramón Gómez Arrayás

  DOI：10.1021/jo972167p

  日期：1998.5.1

  The polyhydroxylated indolizidines castanospermine and swainsonine as well as some of their stereoisomers are powerful glycosidase inhibitors. An efficient and stereochemically flexible synthesis of racemic 1,7,8-trihydroxylated and 1,6,7,8-tetrahydroxylated indolizidines (castanospermine stereoisomers) from readily available N-substituted gamma-oxygenated alpha,beta-unsaturated sulfones 3 and 4 has been developed. The construction of the bicyclic skeleton of 1-hydroxyindolizidine has been accomplished by intramolecular conjugate addition of the nitrogen moiety of 3 and 4 to the alpha,beta-unsaturated sulfone unit to give the pyrrolidine intermediates 5 and 6, followed by formation of the C(7)-C(8) bond by intramolecular acylation (or alkylation) of the alpha-sulfonyl carbanion. The stereoselectivity of the pyrrolidine synthesis was highly dependent on the bulkiness of the gamma-oxygenated function; thus, the free alcohols gave predominantly cis-pyrrolidines while the OTIPS derivatives led to the trans isomers. After straightforward functional group transformations, the removal of the sulfonyl group at C(8) either by Julia reaction or by basic elimination (depending on the substrate used) afforded the key C(7)C(8) unsaturated indolizidines 10, 22, 30, and 31, whose stereoselective dihydroxylations with OsO4 gave a variety of cis C(1)C(8a) and-trans C(1)C(8a) trihydroxylated and tetrahydroxylated indolizidines, among which (+/-)-1,7-di-epi-castanospermine and (+/-)-1,8-di-epi-castanospermine have been reported for the first time.
• Stereoselective synthesis of hydroxypyrrolidines and hydroxypiperidines by cyclization of γ-oxygenated-α,β-unsaturated sulfones
  作者：Juan Carlos Carretero、Ramón Gómez Arrayás、Isabel Storch de Gracia

  DOI：10.1016/0040-4039(96)00551-5

  日期：1996.5

  cis and trans 2,3-disubstituted pyrrolidines and piperidines have been prepared stereoselectively by intramolecular conjugate addition of N-substituted γ-oxygenated-α,β-unsaturated phenyl sulfones. The best cis-selectivities were obtained from the alcohols and the best trans-selectivities from the OTIPS derivatives.

  顺式和反式2，3-二取代的吡咯烷和哌啶已通过分子内共轭添加N-取代的γ-氧化的-α，β-不饱和苯基砜而立体制备。从醇获得最佳的顺式选择性，从OTIPS衍生物获得最佳的反式选择性。