(1S,12bS)-1-ethyl-1-(2-hydroxyethyl)-4-oxo-2,3,6,7,12,12b-hexahydro-1H-indolo[2,3-a]quinolizine | 111687-22-0

• 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: (1S,12bS)-1-ethyl-1-(2-hydroxyethyl)-4-oxo-2,3,6,7,12,12b-hexahydro-1H-indolo[2,3-a]quinolizine
• 英文别名: (1S,12bS)-1-ethyl-1-(2-hydroxyethyl)-1,2,3,6,7,12b-hexahydroindolo[2,3-a]quinolizin-4(12H)-one；(1S,12bS)-1-ethyl-1-(2-hydroxyethyl)-2,3,6,7,12,12b-hexahydroindolo[2,3-a]quinolizin-4-one
• CAS: 111687-22-0
• 化学式: C₁₉H₂₄N₂O₂
• 分子量: 312.412
• InChiKey: YNOQUGHPFMJVAF-MOPGFXCFSA-N

物化性质

• 熔点：
  263-265 °C (decomp)
• 沸点：
  547.3±50.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  56.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1S,12bS)-1-ethyl-1-(2-hydroxyethyl)-4-oxo-2,3,6,7,12,12b-hexahydro-1H-indolo[2,3-a]quinolizine 在 lithium aluminium tetrahydride 、 四丙基高钌酸铵 、 4 A molecular sieve 、 三氧化硫吡啶 、 N-甲基吗啉氧化物 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 23.5h， 生成 长春布宁
  参考文献：
  名称：

  由（4S）-4-乙基-4- [2-（羟羰基）乙基] -2-丁内酯不对称合成（-）-表氨碱和（+）-表氨碱。

  摘要：

  关键的手性非外消旋4,4-二取代的2-丁内酯羧酸（S）-4，可通过重氮丙二酸酯（S）-5的高效且立体有择的四乙酸二氢铑（II）催化的叔CH插入反应获得。酸（S）-4与色胺混合产生酰胺（S）-3，然后将其转化为醛23和羟基内酰胺24。酸介导的23-和24-Pictet-Spengler环化生成四环吲哚内酰胺（1S，12bS）-25a和（1S，12bR）-25b。经由内酰胺醇30a和30b，化合物25a和25b被转化为（-）-金丁胺（1a）和（+）-表金丁胺（1b）。

  DOI：

  10.1021/jo010751z
• 作为产物：
  描述：

  3-(3-Ethyl-2-hydroxy-tetrahydro-furan-3-yl)-N-[2-(1H-indol-3-yl)-ethyl]propionamide 在 sodium hydroxide 作用下， 以 甲醇 、 溶剂黄146 为溶剂， 反应 48.5h， 生成 (1S,12bS)-1-ethyl-1-(2-hydroxyethyl)-4-oxo-2,3,6,7,12,12b-hexahydro-1H-indolo[2,3-a]quinolizine
  参考文献：
  名称：

  Desymmetrization of Benzoic Acid in the Context of the Asymmetric Birch Reduction−Alkylation Protocol. Asymmetric Total Syntheses of (−)-Eburnamonine and (−)-Aspidospermidine

  摘要：

  The highly diastereoselective potassium in ammonia reduction-ethylation (EtI) of the chiral 2-(trimethylsilyl)benzamide 1b to give 1,4-cyclohexadiene 3 is the key step in asymmetric syntheses of (-)-eburnamonine (4) and (-)-aspidospermidine (5). Cyclohexadiene 3 was converted to cyclohexanone 7, which provided the trimethylsilyl-substituted butyrolactone 9 utilized for the synthesis of 4 and butyrolactone 13 required for the synthesis of 5. The preparation of 9 depended upon the completely regioselective silicon-directed Baeyer-Villiger oxidation 7-->8; Baeyer-Villiger oxidation of the cyclohexenone 10 also was regioselective to give the desired enol lactone 11 in 92% yield. Remarkable diastereoselectivity was observed for the kinetically controlled cyclization of the acyl imminium ion derived from the vinyl-substituted carboxaldehyde 16b; treatment of 16b with 5 equiv of CF3CO2H in CH2Cl2 at -55 degrees C gave an 18:1 mixture of 17 and its C(3) beta-epimer in 93% yield. The oxidation of alcohol 18 containing sensitive indole and piperidine rings was best carried out with tetrapropylammonium perruthenate/N-methylmorpholine N-oxide to give (-)-eburnamonine (4) in 97% yield. The asymmetric synthesis of (-)-aspidospermidine 5 involved the conversion of butyrolactone 13 to the hydroxylactam 22, the Harley-Mason cyclization of 22 to 23, and reduction of 23 with LiAlH4.

  DOI：

  10.1021/jo9707592

文献信息

• Enantiospecific total synthesis of indole alkaloids (+)-eburnamonine, (−)-aspidospermidine and (−)-quebrachamine
  作者：John Eugene Nidhiry、Kavirayani R. Prasad

  DOI：10.1016/j.tet.2013.04.097

  日期：2013.7

  An enantiospecific total synthesis of indole alkaloids eburnamonine, aspidospermidine and quebrachamine is described from lactic acid. Synthesis of all three alkaloids is accomplished from a single chiral building block. Johnson–Claisen rearrangement of a chiral allyl alcohol is the main feature for the installation of the required quaternary centre.

  从乳酸描述了对映体的吲哚生物碱氨丁环胺碱，aspspersmidine和quebrachamine的全合成。所有三个生物碱的合成是从一个手性结构单元完成的。Johnson-Claisen手性烯丙醇的重排是安装所需四元中心的主要特征。
• Total synthesis of (−)-eburnamonine and (+)-epi-eburnamonine from a chiral non-racemic 4,4-disubstituted γ-lactone
  作者：Andrew G.H Wee、Qing Yu

  DOI：10.1016/s0040-4039(99)02131-0

  日期：2000.1

  The total synthesis of (−)-eburnamonine and (+)-epi-eburnamonine was successfully achieved using a key chiral non-racemic 4,4-disubstituted γ-lactone 4 that was prepared via the Rh(II) carbenoid mediated tertiary C–H insertion reaction of a chiral non-racemic diazomalonate 5.

  的全合成（ - ） - -象牙酮宁和（+）外延使用密钥手性非外消旋的4,4-二取代的γ内酯成功实现了-eburnamonine 4，其通过所述的Rh（II）卡宾介导的叔C-制备H插入手性非外消旋重氮丙二酸酯5的插入反应。
• Indole alkaloids. A combined chemical and enzymatic route for eburnane ring construction : Formal synthesis of (−)-Eburnamonine
  作者：Giovanni Palmisano、Paolo D'Anniballe、Marco Santagostino

  DOI：10.1016/s0040-4020(01)85522-8

  日期：——

  A stereocontrolled formal synthesis of (−)-eburnamonine 1, a tetracyclic indole alkaloid used as antihypertensive drug, has been achieve through the use of [3,3]-sigmatropic rearrangement (Claisen rearrangement) of the enantiopure β-alkoxy acrylate 4, available from rac-3-ethly-cyclohexenol 3via lipase-catalyzed transesterification

  甲立体控制的正式合成（ - ） -象牙酮宁1，四环吲哚生物碱用作降压药，已通过使用[3,3] -sigmatropic重排（Claisen重排）的对映体纯β -烷氧基丙烯酸酯的实现4，购从rac -3-ethly-cyclohexenol 3通过脂肪酶催化的酯交换反应
• Chiral total synthesis of indole alkaloids of the Aspidosperma and Hunteria types
  作者：Manabu Node、Hideko Nagasawa、Kaoru Fuji

  DOI：10.1021/jo00289a025

  日期：1990.1
• Expeditious enantioselective syntheses of indole alkaloids of Aspidosperma- and Hunteria-type
  作者：Manabu Node、Hideko Nagasawa、Kaoru Fuji

  DOI：10.1021/ja00259a060

  日期：1987.12