methyl 2-[3-[2-(benzylamino)ethyl]-1H-indol-2-yl]-3-hydroxypropanoate | 146681-75-6

• 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: methyl 2-[3-[2-(benzylamino)ethyl]-1H-indol-2-yl]-3-hydroxypropanoate
• CAS: 146681-75-6
• 化学式: C₂₁H₂₄N₂O₃
• 分子量: 352.433
• InChiKey: POUSDFOEOMHGDB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  74.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 2-[3-[2-(benzylamino)ethyl]-1H-indol-2-yl]-3-hydroxypropanoate 在 palladium on activated charcoal 、 镍 diphosphorus pentasulfide 、 氢气 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 溶剂黄146 、 甲苯 为溶剂， 反应 54.0h， 生成 (+/-)-deethylibophyllidine
  参考文献：
  名称：

  长春花生物碱及相关化合物的合成。第 106 部分。构建 Ibophyllidine 骨架 II 的有效收敛合成途径。(±)-Deethylibophylidine 和 (±)-14-Epi-deethylibophylidine 的全合成

  摘要：

  从 5-乙基二氢呋喃-2(3H)-one (9) 开始，我们制备了醛 (6 和 7)，在与色胺衍生物 (8) 的 [4+2] 环加成反应中，作为最后一步，化合物 ( 13和22)具有D-seco-pseudoaspidospermane骨架。我们通过苯甲酸酯 (15) 或醇 (14) 的甲磺酸酯 (17) 合成了 (±)-20-epiibophylidine (4)，从 13 中获得，而 22 的催化加氢得到 (±)-ibophylidine (3) 通过一次操作中的完全差向异构化、环化和还原步骤。

  DOI：

  10.3987/com-06-10845
• 作为产物：
  描述：

  N_b,N_b-dibenzyl-2-(cyanomethyl)tryptamine 在 palladium on activated charcoal 盐酸 、 sodium tetrahydroborate 、 氢气 、 sodium hydride 、 溶剂黄146 作用下， 以 溶剂黄146 为溶剂， 反应 6.0h， 生成 methyl 2-[3-[2-(benzylamino)ethyl]-1H-indol-2-yl]-3-hydroxypropanoate
  参考文献：
  名称：

  Synthesis of vinca alkaloids and related compounds. 63. A new synthetic pathway for preparing alkaloids and related compounds with the aspidosperma skeleton. Total syntheses of (.+-.)-vincadifformine, (.+-.)-tabersonine, and (.+-.)-oxotabersonine

  摘要：

  Compound 3, which has an indole skeleton containing a masked acryl ester function, was synthesized from the hydrochloride of 2-(ethoxycarbonyl)tryptamine (2). The cycloaddition of 3 with methyl 4-formylhexanoate (21) or with 5-(benzoyloxy)-2-ethylpentanal (33) yielded the starting materials for target compounds (+/-)-vincadifformine (4), (+/-)-3-oxotabersonine (42), and (+/-)-tabersonine (43). The synthesis of vincadifformine (4) was achieved in two different ways: via 3-oxovincadifformine (7) and via tetracyclic benzoate esters 37 and 38. The double bond required in tabersonine (43) and 3-oxotabersonine (42) was introduced by treatment of 3-thioxovincadifformine (39) with p-toluenesulfinyl chloride.

  DOI：

  10.1021/jo00058a025

文献信息

• Synthesis of vinca alkaloids and related compounds part 94. Epimerization of compounds with aspidospermane and<i>D</i>-secoaspidospermane skeleton
  作者：György Kalaus、Lajos Szabó、János Éles、Csaba Szántay、Imre Juhász、IstvÁn Greiner、János Brlik、Mária Kajtár-Peredy

  DOI：10.1002/jhet.5570370205

  日期：2000.3

  The individual epimerization steps of vincadifformine (1), deethylvincadifformine isomers (2,3), their synthetic intermediates (4–13) as well as that of simpler compounds with D-secoaspidospermane skeleton (15–17) were studied a) in protic medium (boiling deuteroacetic acidic) and b) under reductive (with sodium borodeuteride in boiling acetic acid, or with sodium borohydride in boiling deuteroacetic

  研究了长春花蕾碱（1），去乙基长春花碱异构体（2,3），其合成中间体（4–13）以及具有D -secoaspidospermane骨架的较简单化合物的个别差向异构化步骤（15–17）a）在质子培养基中（在沸腾的氘代乙酸中）和（b）在还原条件下（在沸腾的乙酸中用硼氘化钠或在沸腾的氘代乙酸中用硼氢化钠）。
• Synthesis of vinca alkaloids and related compounds. Part 102: Simple synthesis and ring transformation of (±)-minovincine. First synthesis of (±)-vincaminine
  作者：György Kalaus、László Léder、István Greiner、Mária Kajtár-Peredy、Károly Vékey、Lajos Szabó、Csaba Szántay

  DOI：10.1016/s0040-4020(03)00902-5

  日期：2003.7

  A molecule with an indole skeleton, containing a latent acrylic ester function—acting as a diene—readily reacted with benzoic acid (4-bromomethylene-5-oxo)hexyl ester that had been built up from pentane-2,4-dione. Dehydration of the enamine and subsequent [4+2] cycloaddition supplied epimers having the d-secoaspidospermane skeleton. These compounds directly or after epimerization gave (±)-minovincine

  具有吲哚骨架的分子具有潜在的丙烯酸酯功能（起二烯作用），该分子易于与由戊烷2,4-二酮建立的苯甲酸（4-溴亚甲基-5-氧代）己酯反应。烯胺的脱水和随后的[4 + 2]环加成反应提供了具有d-半胱氨酸高精链骨架的差向异构体。这些化合物直接或差向异构化后得到（±）-氨基长春新碱。（±）-氨基长春新碱在不同条件下的氧化环转化导致（±）-16-乙酰基-16-脱乙基阿波辛胺和（±）-长春新碱。
• Synthesis of vinca alkaloids and related compounds. Part 101: A new convergent synthetic pathway to build up the aspidospermane skeleton. Simple synthesis of 3-oxovincadifformine and 3-oxominovincine. Attempts to produce 15β-hydroxyvincadifformine
  作者：János Éles、György Kalaus、István Greiner、Mária Kajtár-Peredy、Pál Szabó、Lajos Szabó、Csaba Szántay

  DOI：10.1016/s0040-4020(02)01179-1

  日期：2002.10

  A molecule with an indole skeleton, containing a latent acrylic ester function—acting as a diene—was produced from Nb-trityl-2-(hydroxy-methyl)-tryptamine and reacted with esters containing an aldehyde or aldehyde-equivalent structural unit, yielding 3-oxo-16,17-dihydro-Δ20-secodin-17-ol type intermediates from which dehydration, followed by [4+2]cycloaddition, furnished 3-oxovincadifformine and 3-oxominovincine

  由N b-三苯甲基-2-（羟基-甲基）-色胺产生具有吲哚骨架的分子，该分子具有潜在的丙烯酸酯功能（起二烯作用），并与含有醛或醛当量结构单元的酯反应，得到3-氧代-16,17-二氢- Δ 20 -secodin -17-醇型中间体从脱水，接着[4 + 2]环加成，陈设3- oxovincadifformine和3- oxominovincine。我们还希望将该方法用于生产15β-羟基长春新碱，但是，观察到具有吲哚骨架的二聚产物的出现，而不是预期的环加成。
• Synthesis of Vinca Alkaloids and Related Compound 103. Recognition of an Unexpected Reaction and Its Application in Building the Aspidospermane Skeleton. Simple Synthesis of 15b-Hydroxyvincadifformine
  作者：György Kalaus、Flórián Tóth、István Greiner、Mária Kajtár-Peredy、Ágnes Gömöry、László Hazai、Csaba Szántay

  DOI：10.3987/com-05-10603

  日期：——

  Reaction of tryptamine derivative (2b) and acetate ester (11) built up from 2-(chloromethylene)butanal (4) resulted in enamino ketone (14). Dehydration of 14 and subsequent intramolecular [4+2] cycloaddition led to 15-oxovincadifformine (15). Regio- and stereoselective reduction of the latter molecule supplied 15β-hydroxyvincadifformine (1).

  色胺衍生物 (2b) 和由 2-(氯亚甲基) 丁醛 (4) 形成的乙酸酯 (11) 反应生成烯胺酮 (14)。14 的脱水和随后的分子内 [4+2] 环加成导致 15-oxovincadifformine (15)。后一种分子的区域选择性和立体选择性还原提供了 15β-羟基长春二甲双胍 (1)。
• Synthesis of vinca alkaloids and related compounds. Part 105: Efficient convergent synthetic pathway to the ibophyllidine skeleton and synthesis of (±)-19-hydroxy-ibophyllidine and (±)-19-hydroxy-20-epiibophyllidine
  作者：Flórián Tóth、György Kalaus、István Greiner、Mária Kajtár-Peredy、Ágnes Gömöry、László Hazai、Csaba Szántay

  DOI：10.1016/j.tet.2006.09.079

  日期：2006.12

  Starting from methyl-5-oxohexanoate we produced the appropriately functionalized aldehyde, which, after having been allowed to react with the tryptamine derivative in a [4+2] cycloaddition reaction as the final step, yielded the molecule containing a D-seco-aspidospermane skeleton. From the latter we could successfully produce a 1:1 mixture of protected epimers, the desilylation reaction of the protected

  从-5-氧代己酸甲酯开始，我们生成了适当官能化的醛，在最后一步使它与色胺胺衍生物在[4 + 2]环加成反应中反应后，得到包含D-seco-aspidospermane的分子骨骼。从后者我们可以成功产生受保护的差向异构体的1：1混合物，受保护分子的去甲硅烷基化反应以高收率获得了生物碱（±）-19-羟基-异波西啶和（±）-19-羟基-20-异波西啶。