trans-2-benzyl-3-(methoxycarbonyl)-1-methyl-1,2,3,4-tetrahydro-9H-pyrido<3,4-b>indole | 93712-66-4

• 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: trans-2-benzyl-3-(methoxycarbonyl)-1-methyl-1,2,3,4-tetrahydro-9H-pyrido<3,4-b>indole
• 英文别名: trans-2-benzyl-3-methoxycarbonyl-1-methyl-1,2,3,4-tetrahydro-9H-pyrido<3,4-b>indole；trans-2-benzyl-3-methoxycarbonyl-1-methyl-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole；Methyl (1RS,3SR)-trans-2-benzyl-1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylate；methyl (1S,3R)-2-benzyl-1-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indole-3-carboxylate
• CAS: 93712-66-4
• 化学式: C₂₁H₂₂N₂O₂
• 分子量: 334.418
• InChiKey: ZZPIZYDWDIBMNG-IFXJQAMLSA-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：

  trans-2-benzyl-3-(methoxycarbonyl)-1-methyl-1,2,3,4-tetrahydro-9H-pyrido<3,4-b>indole 在 palladium on activated charcoal 甲酸铵 作用下， 以 甲醇 为溶剂， 以96%的产率得到methyl (1S,3R)-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate
  参考文献：
  名称：

  通过Pictet-Spengler反应对反式1,3-二取代的四氢-β-咔啉的对映体形成，以及通过C-1 / N-2键的断裂将顺式非对映异构体转化为反式对映体。

  摘要：

  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

  DOI：

  10.1021/jo951170a
• 作为产物：
  描述：

  (1S,3S)-methyl 2-benzyl-1-methyl-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙腈 为溶剂， 反应 25.0h， 以94%的产率得到trans-2-benzyl-3-(methoxycarbonyl)-1-methyl-1,2,3,4-tetrahydro-9H-pyrido<3,4-b>indole
  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

文献信息

• Tetrahydro-.beta.-carboline dithioic acid derivatives and treatment of
  申请人：Tanabe Seiyaku Co., Ltd.

  公开号：US04612317A1

  公开（公告）日：1986-09-16

  Tetrahydro-.beta.-carboline derivatives of the formula: ##STR1## wherein R.sup.1 is hydrogen atom, a lower alkyl group, a cycloalkyl group, phenyl group or a hydroxy-substituted lower alkyl group, R.sup.2 is hydrogen atom, an alkyl group, or a group of the formula: --(CH.sub.2).sub.m Y, Y is thienyl or a substituted or unsubstituted phenyl group, and m and n are an integer of 1 or 2, which have excellent alleviating, curing and preventing hepatic damages and are useful as a therapeutic or prophylactic agent for hepatic diseases, and a process for the preparation of said compounds.

  Tetrahydro-.beta.-carboline衍生物的化学式如下：##STR1##其中R.sup.1是氢原子，较低的烷基基团，环烷基基团，苯基或羟基取代的较低烷基基团，R.sup.2是氢原子，烷基基团，或化学式--(CH.sub.2).sub.m Y的基团，Y是噻吩基或取代或未取代的苯基团，m和n是1或2的整数，这些化合物具有出色的缓解、治愈和预防肝损伤的作用，并可用作治疗或预防肝病的药物，以及制备上述化合物的方法。
• Tetrahydro-.beta.-carboline derivatives and treatment of liver diseases
  申请人：Tanabe Seiyaku Co., Ltd.

  公开号：US04628057A1

  公开（公告）日：1986-12-09

  Novel tetrahydro-.beta.-carboline derivatives of the formula: ##STR1## wherein R.sup.1 is carboxyl, a lower alkoxycarbonyl, carbamoyl, an N,N-di-lower alkylcarbamoyl, an N-(phenyl-substituted lower alkylidenamino)carbamoyl, a [N,N-di(lower alkyl)amino]-lower alkyl, or a nitrogen-containing monocyclic heterocyclic group; R.sup.2 is hydrogen atom, a lower alkyl, or a hydroxy-lower alkyl group, or R.sup.2 is combined with R.sup.1 to form a group: --CO--O--CH.sub.2 --; R.sup.3 is hydrogen atom, a lower alkyl, a phenyl-lower alkyl, or a group: --CSS--R.sup.4 ; R.sup.4 is hydrogen atom, an alkyl, or a group: --(CH.sub.2).sub.n Y.sup.1 ; n is 0, 1 or 2, Y.sup.1 is a lower alkenyl, a phenyl-substituted lower alkenyl, an N,N-di(lower alkyl)amino, a lower alkylmercapto, a lower alkoxycarbonyl, benzoyl, naphthyl, a cycloalkyl, a monocyclic heterocyclic group, or a substituted or unsubstituted phenyl, which have excellent activities for alleviating, curing and preventing hepatic damages and are useful as a therapeutic or prophylactic agent for hepatic diseases, and processes for the preparation thereof, and a pharmaceutical composition containing the above compound as an active ingredient.

  该专利描述了一种新型的四氢-β-咔啉衍生物，其化学式为：##STR1## 其中R.sup.1为羧基、较低的烷氧羰基、氨基甲酰基、N,N-二较低烷基氨基甲酰基、N-(苯基取代的较低烷基亚氨基)甲酰基、[N,N-二(较低烷基)氨基]-较低烷基，或含氮的单环杂环基团；R.sup.2为氢原子、较低的烷基，或羟基较低烷基基团，或R.sup.2与R.sup.1结合形成一个基团：--CO--O--CH.sub.2 --；R.sup.3为氢原子、较低的烷基、苯基较低烷基，或一个基团：--CSS--R.sup.4；R.sup.4为氢原子、烷基，或一个基团：--(CH.sub.2).sub.n Y.sup.1；n为0、1或2，Y.sup.1为较低烯基、苯基取代的较低烯基、N,N-二(较低烷基)氨基、较低烷基硫醇基、较低的烷氧羰基、苯甲酰基、萘基、环烷基、单环杂环基团，或取代或未取代的苯基，这些化合物对缓解、治愈和预防肝损伤具有出色的活性，并可用作治疗或预防肝病的药物，以及其制备方法和含有上述化合物作为活性成分的药物组合物。
• 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
• A new method for the preparation of 3,4-dihydro - and 1,2,3,4-tetrahydro-.BETA.-carbolines.
  作者：AKIHIKO ISHIDA、TOHRU NAKAMURA、KUNIHIKO IRIE、TOKURO OHISHI

  DOI：10.1248/cpb.33.3237

  日期：——

  N-Alkylthiocarbonyltryptophan (2a-i) and tryptamine (2j-m) derivatives can be converted into the corresponding 3, 4-dihydro-β-carbolines (3) under mild conditions by the use of alkylating or acylating agents. The NaBH4 reduction of 1, 3-disubstituted 3, 4-dihydro-β-carbolines (3a-i) gave cis- (5) or trans-1, 2, 3, 4-tetrahydro-β-carbolines (6) with satisfactory stereoselectivity. The synthesis of optically active 3a, b and 5a, b is also described.

  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。
• Brønsted Acid Mediated Cyclization of Enaminones. Rapid and Efficient Access to the Tetracyclic Framework of the <i>Strychnos</i> Alkaloids
  作者：Rahul V. Edwankar、Chitra R. Edwankar、Ojas A. Namjoshi、Jeffrey R. Deschamps、James M. Cook

  DOI：10.1021/np200759h

  日期：2012.2.24

  ma alkaloids is described. Enaminone 16, synthesized in high yield, has been cyclized under the influence of a Brønsted acid to provide the core tetracyclic framework 17 of the Strychnos alkaloids in optically active form or alternatively to the β-ketoester tetrahydro-β-carboline (THBC) unit 18, by varying the equivalents of acid and the molar concentration. Attempts to utilize 18 to form the C(7)–C(16)

  其允许四环核心的快速施工高效的非对映选择性方法的开发17所述的马钱子-白坚木属生物碱进行说明。以高产率合成的烯胺酮16已在布朗斯台德酸的影响下环化，以提供旋光形式的马钱子生物碱的核心四环骨架17或替代 β-酮酯四氢-β-咔啉 (THBC) 单元18，通过改变酸的当量和摩尔浓度。尝试利用18形成以严格胺为代表的 akuammiline 相关生物碱的 C(7)–C(16) 键 ( 22)，使用金属卡宾化学，也被描述。