(4aR-(4aα,8aβ))-4a-ethyl-6-[2-(1H-indol-3-yl)ethyl]octahydro-2,5-pyrano[3,2-c]pyridinedione | 190378-30-4

• 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: (4aR-(4aα,8aβ))-4a-ethyl-6-[2-(1H-indol-3-yl)ethyl]octahydro-2,5-pyrano[3,2-c]pyridinedione
• 英文别名: (4aR,8aS)-4a-ethyl-6-[2-(1H-indol-3-yl)ethyl]-4,7,8,8a-tetrahydro-3H-pyrano[3,2-c]pyridine-2,5-dione
• CAS: 190378-30-4
• 化学式: C₂₀H₂₄N₂O₃
• 分子量: 340.422
• InChiKey: NOIYTUMBIXSETQ-FXAWDEMLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.04
• 重原子数：
  25.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  62.4
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (4aR-(4aα,8aβ))-4a-ethyl-6-[2-(1H-indol-3-yl)ethyl]octahydro-2,5-pyrano[3,2-c]pyridinedione 在 palladium on activated charcoal ammonium hydroxide 、 氢气 、 lithium perchlorate 、 三氯氧磷 作用下， 生成 (4aS,13bS,13cS)-13c-Ethyl-1,2,4a,5,6,7,8,13,13b,13c-decahydro-4-oxa-6a,13-diaza-indeno[1,2-c]phenanthren-3-one 、 (14bS-(14bβ,14cα))-14c-ethyl-2,3,4a,5,6,8,9,14,14b,14c-decahydro-3-1H-indolo[2,3-a]pyrano[2,3-h]quinolizinone
  参考文献：
  名称：

  Stereocontrolled Elaboration of Quaternary Carbon Centers through the Asymmetric Michael-Type Alkylation of Chiral Imines/Secondary Enamines:  Enantioselective Synthesis of (+)-Vincamine

  摘要：

  An enantioselective synthesis of (+)-vincamine (1) has been developed. The key strategic element was the stereocontrolled elaboration of a quaternary carbon center (future C-20 center of 1) by using the asymmetric Michael reaction involving chiral imines/secondary enamines under neutral conditions. Thus, addition of enaminolactam (S)-12, derived from ketolactam 7 (itself prepared in four steps from commercially available tryptamine) and (S)-1-phenylethylamine, to methyl acrylate led, after hydrolytic workup, to adduct (R)-6 with a 90% stereoselectivity. The critical removal of the additional keto group of 6 was then examined. After extensive experimentation, we finally established that the most efficient deoxygenation procedure was the Wolff-Kishner reduction of the corresponding keto acid, which proceeded with a 55% yield. The cornerstone [ABD]-tricyclic lactam ester 38 thus obtained was next cyclized under Bischler-Napieralski reaction conditions to afford, after catalytic hydrogenation of the intermediary iminium perchlorate salt, a mixture of the desired, known indoloquinolizidine 5 and its epimer 39, in a ratio of 6:1, respectively. Basic treatment of 5 led to (+)-homoeburnamonine 4, which was finally converted, according to a known procedure, into our goal (+)-vincamine (1). Thus, synthesis of (+)-vincamine (1) has been achieved by a linear sequence of 15 chemical operations, starting from tryptamine, with an overall yield of 1.2%.

  DOI：

  10.1021/jo9622690
• 作为产物：
  描述：

  5-ethyl-1-[2-(1H-indol-3-yl)ethyl]-4-hydroxy-6-oxo-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid ethyl ester 在 Amberlyst R₁₅ 、 水 、 对甲苯磺酸 、 溶剂黄146 、 lithium tri-t-butoxyaluminum hydride 、 对苯二酚 、 lithium bromide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 甲苯 、 苯 为溶剂， 反应 112.0h， 生成 (4aR-(4aα,8aβ))-4a-ethyl-6-[2-(1H-indol-3-yl)ethyl]octahydro-2,5-pyrano[3,2-c]pyridinedione
  参考文献：
  名称：

  Stereocontrolled Elaboration of Quaternary Carbon Centers through the Asymmetric Michael-Type Alkylation of Chiral Imines/Secondary Enamines:  Enantioselective Synthesis of (+)-Vincamine

  摘要：

  An enantioselective synthesis of (+)-vincamine (1) has been developed. The key strategic element was the stereocontrolled elaboration of a quaternary carbon center (future C-20 center of 1) by using the asymmetric Michael reaction involving chiral imines/secondary enamines under neutral conditions. Thus, addition of enaminolactam (S)-12, derived from ketolactam 7 (itself prepared in four steps from commercially available tryptamine) and (S)-1-phenylethylamine, to methyl acrylate led, after hydrolytic workup, to adduct (R)-6 with a 90% stereoselectivity. The critical removal of the additional keto group of 6 was then examined. After extensive experimentation, we finally established that the most efficient deoxygenation procedure was the Wolff-Kishner reduction of the corresponding keto acid, which proceeded with a 55% yield. The cornerstone [ABD]-tricyclic lactam ester 38 thus obtained was next cyclized under Bischler-Napieralski reaction conditions to afford, after catalytic hydrogenation of the intermediary iminium perchlorate salt, a mixture of the desired, known indoloquinolizidine 5 and its epimer 39, in a ratio of 6:1, respectively. Basic treatment of 5 led to (+)-homoeburnamonine 4, which was finally converted, according to a known procedure, into our goal (+)-vincamine (1). Thus, synthesis of (+)-vincamine (1) has been achieved by a linear sequence of 15 chemical operations, starting from tryptamine, with an overall yield of 1.2%.

  DOI：

  10.1021/jo9622690