(1S,3S)-methyl 2-benzyl-1-methyl-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate | 91185-15-8

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: (1S,3S)-methyl 2-benzyl-1-methyl-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate
• 英文别名: methyl (1S,3S)-2-benzyl-1-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indole-3-carboxylate
• CAS: 91185-15-8
• 化学式: C₂₁H₂₂N₂O₂
• 分子量: 334.418
• InChiKey: ZZPIZYDWDIBMNG-LIRRHRJNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  45.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1S,3S)-methyl 2-benzyl-1-methyl-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate 在 palladium 10% on activated carbon 、 氢气 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙腈 为溶剂， 60.0~81.0 ℃ 、111.47 kPa 条件下， 反应 33.0h， 生成 methyl (1S,3R)-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate
  参考文献：
  名称：

  Highly stereoselective transformation of (1S,3S)-cis-1,3-disubstituted tetrahydro-β-carbolines into (1S,3R)-trans-1,3-disubstituted tetrahydro-β-carbolines: an improved asymmetric synthesis of tadalafil from l-tryptophan

  摘要：

  An efficient and general method for the highly stereoselective transformation of (1S,3S)-cis-1,3-disubstituted 1,2,3,4-tetrahydro-beta-carbolines (THBCs) into (15,3R)-trans-1,3-disubstituted THBCs is described. The method contains the following three steps: the enantiomerically pure (1S,3S)-cis-1,3-disubstituted THBCs 1 were first converted into (1S,3S)-cis-1,2,3-trisubstituted THBCs 2 by N-1-naphthylmethylation/benzylation; (15,3S)-cis-1,2,3-trisubstituted THBCs 2 were then converted into (1S,3R)-trans-1,2,3-trisubstituted THBCs 3 in high yields and with high stereoselectivities via a base-catalyzed epimerization at C-3; (1S,3R)-trans-1,2,3-trisubstituted THBCs 3 were subsequently converted into (15,3R)-trans-1,3-disubstituted THBCs 4 after reductive removal of the 1-naphthylmethyl/benzyl group. In addition, as an application of this method, an improved and highly stereoselective synthesis of the PDE5 inhibitor tadalafil (Cialis (R)) starting from natural and less expensive L-tryptophan was developed. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2013.06.006
• 作为产物：
  描述：

  2-(Acetyl-benzyl-amino)-3-(1H-indol-3-yl)-propionic acid methyl ester 在 劳森试剂 、 sodium tetrahydroborate 、 碘甲烷 作用下， 以 甲醇 、 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 28.0h， 生成 (1S,3S)-methyl 2-benzyl-1-methyl-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate
  参考文献：
  名称：

  A new method for the preparation of 3,4-dihydro - and 1,2,3,4-tetrahydro-.BETA.-carbolines.

  摘要：

  N-烷基硫羰基色氨酸（2a-i）和色氨酸（2j-m）衍生物可以在温和条件下通过烷基化或酰基化剂转化为相应的3, 4-二氢-β-氨基吲哚（3）。1, 3-二取代的3, 4-二氢-β-氨基吲哚（3a-i）经过NaBH4还原，得到了具有满意立体选择性的顺式（5）或反式-1, 2, 3, 4-四氢-β-氨基吲哚（6）。本文还描述了外消旋活性3a, b和5a, b的合成。

  DOI：

  10.1248/cpb.33.3237

文献信息

• Enantiospecific Formation of <i>Trans</i> 1,3-Disubstituted Tetrahydro-β-carbolines by the Pictet−Spengler Reaction and Conversion of <i>Cis</i> Diastereomers into Their <i>Trans</i> Counterparts by Scission of the C-1/N-2 Bond
  作者：Eric D. Cox、Linda K. Hamaker、Jin Li、Peng Yu、Kevin M. Czerwinski、Li Deng、Dennis W. Bennett、James M. Cook、William H. Watson、Mariusz Krawiec

  DOI：10.1021/jo951170a

  日期：1997.1.1

  experiments in TFA. Conversion of the cis diastereomers into the more stable trans diastereomers is believed to occur under acidic conditions by cleavage of the carbon (C-1)-nitrogen (N-2) bond with complete retention of configuration at the C-3 stereocenter. Evidence from deuterium exchange experiments as well as optical rotations support this model for epimerization. In addition, when cis diastereomer

  影响反式-1-烷基-2-苄基-3-（烷氧羰基）-1,2,3,4-四氢-β-咔啉和反式-3-（烷氧羰基）-1-烷基-的立体选择性形成的因素通过在非质子和酸性条件下，将色氨酸衍生物与空间位阻不同的醛加热色氨酸衍生物，然后测定Pictet-Spengler环化法制得的2-（二苯基甲基）-1,2,3,4-四氢-β-咔啉顺式至反式非对映体如此形成。在N（b）-氮原子上存在苄基时，当用环己烷甲醛进行环化反应时，该缩合反应的非对映化学结果会改变，从而提供100％的反式立体选择性。此外，当N（b）-（二苯甲基）色氨酸异丙酯与任意大小的醛缩合时，反式非对映异构体以100％的立体选择性形成。如TFA中的平衡实验所示，反式N（b）-取代的非对映异构体在热力学上比其顺式同类物更稳定。据信，顺式非对映异构体向更稳定的反式非对映异构体的转化是在酸性条件下通过裂解碳（C-1）-氮（N-2）键并完全保留C-3立体中心的构
• TCCA-mediated oxidative rearrangement of tetrahydro-β-carbolines: facile access to spirooxindoles and the total synthesis of (±)-coerulescine and (±)-horsfiline
  作者：Manda Sathish、Akash P. Sakla、Fabiane M. Nachtigall、Leonardo S. Santos、Nagula Shankaraiah

  DOI：10.1039/d1ra02381k

  日期：——

  Multi-reactive centered reagents are beneficial in chemical synthesis due to their advantage of minimal material utilization and formation of less by-products. Trichloroisocyanuric acid (TCCA), a reagent with three reactive centers, was employed in the synthesis of spirooxindoles through the oxidative rearrangement of various N-protected tetrahydro-β-carbolines. In this protocol, low equivalents of

  多反应中心试剂由于其材料利用率最低和副产物形成较少的优点而在化学合成中是有益的。三氯异氰尿酸 (TCCA) 是一种具有三个反应中心的试剂，可通过各种N保护的四氢-β-咔啉的氧化重排来合成螺氧吲哚。在该协议中，需要低当量的 TCCA 才能获得具有广泛底物范围的螺氧吲哚（高达 99% 的产率）。此外，该协议的适用性和稳健性已被证明可用于以优异的产量合成 (±)-coerulescine ( 1 ) 和 (±)-horsfiline ( 2 )等天然生物碱的克级全合成。
• Stereospecificity in the Pictet-Spengler reaction kinetic vs thermodynamic control
  作者：Li Deng、Kevin Czerwinski、James M. Cook

  DOI：10.1016/0040-4039(91)80847-y

  日期：1991.1

  intermediates 1–3 in this condensation are described. Moreover, Pictet-Spengler reaction of 4 or 10 with aldehydes (Ph, Δ) led to kinetic trapping of the cis/trans diastereomers, whereas reaction in TFA/CH2Cl2(25°C) provided tetrahydro β-carbolines via thermodynamic control and increased trans diastereoselectivity in most cases.

  N b-苄基色氨酸甲酯4与5在回流的苯中的Pictet-Spengler反应生成顺式和反式四氢β-咔啉的比例为7a（23）/ 7b（77）的混合物，而异丙基的类似反应具有5的酯10提供增加的反式立体选择性[顺式（13）：反式（87）]。描述了有关中间体1–3在这种缩合反应中的作用的含义。此外，4或10与醛（Ph，Δ）的Pictet-Spengler反应导致顺式/反式非对映异构体的动力学俘获，而在TFA / CH 2 Cl中的反应2（25°C）在大多数情况下通过热力学控制提供了四氢β-咔啉，并提高了反式非对映选择性。
• Pictet–Spengler reaction: is carbonyl the best choice? A highly diastereoselective alternative approach to trans-1,3-disubstituted tetrahydro-β-carbolines
  作者：Kamaljit Singh、Prasant K Deb

  DOI：10.1016/s0040-4039(00)00751-6

  日期：2000.6

  Unprecedented 1,2,3-trisubstituted tetrahydro-beta-carbolines (THBCs) have been synthesized via a short and highly diastereoselective synthetic route. The key step of the sequence is a flexible variant of the Pictet-Spengler reaction employing synthetic equivalents of several non-available carbonyl compounds. Using one such synthon, the resultant THBC could be further ring-closed to a tetracyclic indole alkaloidal skeleton. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Pictet-Spengler reactions in aprotic media. Stereospecificity in the Pictet-Spengler reaction
  作者：Joseph Sandrin、Sean P. Hollinshead、James M. Cook

  DOI：10.1021/jo00284a049

  日期：1989.11