(S)-3-((3R,5S)-3-Ethyl-5-methyl-2-oxo-tetrahydro-furan-3-yl)-3-methoxy-propionic acid | 186887-42-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (S)-3-((3R,5S)-3-Ethyl-5-methyl-2-oxo-tetrahydro-furan-3-yl)-3-methoxy-propionic acid
• 英文别名: (3S)-3-[(3R,5S)-3-ethyl-5-methyl-2-oxooxolan-3-yl]-3-methoxypropanoic acid
• CAS: 186887-42-3
• 化学式: C₁₁H₁₈O₅
• 分子量: 230.261
• InChiKey: ZDWZOXHXDLBTIV-DKCNOQQISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

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)-3-methoxy-propionic acid 在 4-二甲氨基吡啶 、 叠氮磷酸二苯酯 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 3-{2-[(S)-3-((3R,5S)-3-Ethyl-5-methyl-2-oxo-tetrahydro-furan-3-yl)-3-methoxy-propionylamino]-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：

  (4S,5R,7S)-5-Ethyl-4-methoxy-5-((S)-2-methoxymethyl-pyrrolidine-1-carbonyl)-7-methyl-oxepan-2-one 在 对甲苯磺酸 作用下， 以 苯 为溶剂， 以78%的产率得到(S)-3-((3R,5S)-3-Ethyl-5-methyl-2-oxo-tetrahydro-furan-3-yl)-3-methoxy-propionic acid
  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

文献信息

• 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
  作者：Arthur G. Schultz、William P. Malachowski、You Pan

  DOI：10.1021/jo961603p

  日期：1997.3.1

  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.