(S)-3-((3R,5S)-3-Ethyl-5-methyl-2-oxo-tetrahydro-furan-3-yl)-N-[2-(1H-indol-3-yl)-ethyl]-3-methoxy-propionamide | 186887-44-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (S)-3-((3R,5S)-3-Ethyl-5-methyl-2-oxo-tetrahydro-furan-3-yl)-N-[2-(1H-indol-3-yl)-ethyl]-3-methoxy-propionamide
• 英文别名: (3S)-3-[(3R,5S)-3-ethyl-5-methyl-2-oxooxolan-3-yl]-N-[2-(1H-indol-3-yl)ethyl]-3-methoxypropanamide
• CAS: 186887-44-5
• 化学式: C₂₁H₂₈N₂O₄
• 分子量: 372.464
• InChiKey: PLVXIQLTBPKFNX-DHUIEDIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  80.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-3-((3R,5S)-3-Ethyl-5-methyl-2-oxo-tetrahydro-furan-3-yl)-N-[2-(1H-indol-3-yl)-ethyl]-3-methoxy-propionamide 在 4-二甲氨基吡啶 、 锂硼氢 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 0.5h， 生成 3-[2-((3S,4S,6S)-4-Ethyl-6-hydroxy-4-hydroxymethyl-3-methoxy-heptanoylamino)-ethyl]-indole-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Asymmetric Total Synthesis of (+)-Apovincamine and a Formal Synthesis of (+)-Vincamine. Demonstration of a Practical “Asymmetric Linkage” between Aromatic Carboxylic Acids and Chiral Acyclic Substrates

  摘要：

  Asymmetric syntheses of (+)-apovincamine (1a) and (+)-vincamine (2) are described. Construction of the pentacyclic diene lactam 14, a pivotal intermediate for synthesis of the cis-fused vincane-type alkaloids, began by Birch reduction-alkylation of the chiral benzamide 3 to give the 6-ethyl-1-methoxy-4-methyl-1,4-cyclohexadiene 4. Conversion of 4 to 2,5-cyclohexadienone 5 (92% overall yield from 3) and HPLC analysis of 5 demonstrated the diastereomeric purity resulting from the Birch reduction-alkylation to be >100:1. Dienone 5 was converted to butyrolactone 9 (47% overall yield from 3), and 9 was coupled with tryptamine (10) to give the amide 11a. Amido keto aldehyde 13 was obtained from 11a, and acid-catalyzed tricyclization and subsequent base-induced elimination of MeOH provided the desired cis-fused pentacyclic diene lactam 14. Examination of the two-step process 13 --> 14 revealed a novel base-induced epimerization at C(21) which served to interconvert 14 and 17, possibly by the involvement of a homoenolate. Diene lactam 14 was converted to (+)-apovincaminal 20a, an intermediate in the synthesis of (+)-apovincamine (1a) reported by Winterfeldt and co-workers. A new procedure for conversion of 20a to 1a involves conversion of 20a to the acetal 20b and treatment of 20b with NBS/AIBN in CCl4. The conversion of 1a to vincamine (2) has been reported by Oppolzer and co-workers.

  DOI：

  10.1021/jo961603p
• 作为产物：
  描述：

  色胺 、 (S)-3-((3R,5S)-3-Ethyl-5-methyl-2-oxo-tetrahydro-furan-3-yl)-3-methoxy-propionic acid 在 叠氮磷酸二苯酯 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以83%的产率得到(S)-3-((3R,5S)-3-Ethyl-5-methyl-2-oxo-tetrahydro-furan-3-yl)-N-[2-(1H-indol-3-yl)-ethyl]-3-methoxy-propionamide
  参考文献：
  名称：

  Asymmetric Total Synthesis of (+)-Apovincamine and a Formal Synthesis of (+)-Vincamine. Demonstration of a Practical “Asymmetric Linkage” between Aromatic Carboxylic Acids and Chiral Acyclic Substrates

  摘要：

  Asymmetric syntheses of (+)-apovincamine (1a) and (+)-vincamine (2) are described. Construction of the pentacyclic diene lactam 14, a pivotal intermediate for synthesis of the cis-fused vincane-type alkaloids, began by Birch reduction-alkylation of the chiral benzamide 3 to give the 6-ethyl-1-methoxy-4-methyl-1,4-cyclohexadiene 4. Conversion of 4 to 2,5-cyclohexadienone 5 (92% overall yield from 3) and HPLC analysis of 5 demonstrated the diastereomeric purity resulting from the Birch reduction-alkylation to be >100:1. Dienone 5 was converted to butyrolactone 9 (47% overall yield from 3), and 9 was coupled with tryptamine (10) to give the amide 11a. Amido keto aldehyde 13 was obtained from 11a, and acid-catalyzed tricyclization and subsequent base-induced elimination of MeOH provided the desired cis-fused pentacyclic diene lactam 14. Examination of the two-step process 13 --> 14 revealed a novel base-induced epimerization at C(21) which served to interconvert 14 and 17, possibly by the involvement of a homoenolate. Diene lactam 14 was converted to (+)-apovincaminal 20a, an intermediate in the synthesis of (+)-apovincamine (1a) reported by Winterfeldt and co-workers. A new procedure for conversion of 20a to 1a involves conversion of 20a to the acetal 20b and treatment of 20b with NBS/AIBN in CCl4. The conversion of 1a to vincamine (2) has been reported by Oppolzer and co-workers.

  DOI：

  10.1021/jo961603p