(1R,3S)-methyl 1-cyclohexyl-1,2,3,4-tetrahydro-9H-pyrido<3,4-b>indole-3-carboxylate | 91200-23-6

• 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: (1R,3S)-methyl 1-cyclohexyl-1,2,3,4-tetrahydro-9H-pyrido<3,4-b>indole-3-carboxylate
• 英文别名: (1R,3S)-methyl 1-cyclohexyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate；methyl (1R,3S)-1-cyclohexyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate；(1R,3S)-methyl 1-cyclohexyl-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate
• CAS: 91200-23-6
• 化学式: C₁₉H₂₄N₂O₂
• 分子量: 312.412
• InChiKey: KOLPHMYBGCHLFW-DLBZAZTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 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：
  54.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1R,3S)-methyl 1-cyclohexyl-1,2,3,4-tetrahydro-9H-pyrido<3,4-b>indole-3-carboxylate 在 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 28.0h， 生成 (6R,12aS)-6-cyclohexyl-2,3,6,7,12,12a-hexahydropyrazino[1,2-b]β-carboline-1,4-dione
  参考文献：
  名称：

  The fate of the tryptophan stereocenter in the synthesis of 7,10,16,16a-tetrahydro-11H-quinazolino[2′,3′:3,4]pyrazino[1,2-b]β-carboline-5,8-diones

  摘要：

  Condensation reactions of anthranilic acid with iminoethers 14-17 derived from tetracycles 9-13 to give the title hexacyclic compounds reflect a preferred trans-relationship for H(10)-H(16a) protons in C(7)-unsubstituted products and a cis-relatioship for H(7)-H(16a) protons in C(10)-unsubstituted analogs. This synthetic strategy is limited by the steric hindrance of the substituent at C(10). Theoretical calculations are in agreement with the experimental results. The regioselectivity in favor of the linear tetracyclic compound 11 with respect to 12 has also been confirmed. (C) 2000 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0957-4166(00)00282-2
• 作为产物：
  描述：

  Methyl N-(diphenylmethyl)-D,L-tryptophanate 在 palladium on activated charcoal ammonium formate 、 三氟乙酸 作用下， 以 甲醇 、 苯 为溶剂， 反应 72.0h， 生成 (1R,3S)-methyl 1-cyclohexyl-1,2,3,4-tetrahydro-9H-pyrido<3,4-b>indole-3-carboxylate
  参考文献：
  名称：

  Mechanism driven trans stereospecificity in the Pictet-Spengler reaction. Stereospecific formation of trans-1,2,3-trisubstituted-tetrahydro β- carbolines by condensation of Nb-diphenylmethyl tryptophan isopropyl esters wtm aldehydes

  摘要：

  Stereoelectronic control in the Pictet-Spengler condensation of N(b)-alkylsubstituted tryptophan alkyl esters has been employed to promote 100% stereoselectivity in this process. The reaction of N(b)-diphenylmethyl tryptophan isopropyl ester 8 with acetaldehyde in benzene at reflux yielded the trans-diastereomer 10d to the complete exclusion of the corresponding cis isomer. This trans stereospecificity was also observed for butyraldehyde and cyclohexylcarboxaldehyde.

  DOI：

  10.1016/s0040-4039(00)61268-6

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
• Syntheses of tetrahydro-β-carbolines via a tandem hydroformylation–Pictet–Spengler reaction. Scope and limitations
  作者：Bojan P. Bondzic、Peter Eilbracht

  DOI：10.1039/b809157a

  日期：——

  A novel one-pot synthesis of tetrahydro-beta-carboline systems via tandem hydroformylation-Pictet-Spengler reaction starting from olefins and aryl ethylamines is described. This tandem procedure allows fast and convenient synthesis of various substituted tetrahydro-beta-carbolines.

  描述了一种通过一锅加氢甲酰化-Pictet-Spengler反应从烯烃和芳基乙胺开始的一锅合成四氢-β-咔啉系统的方法。该串联程序允许快速方便地合成各种取代的四氢-β-咔啉。
• 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。
• Questioning the γ-gauche effect: stereoassignment of 1,3-disubstituted-tetrahydro-β-carbolines using ¹H–¹H coupling constants
  作者：Kristýna Cagašová、Maryam Ghavami、Zhong-Ke Yao、Paul R. Carlier

  DOI：10.1039/c9ob01139k

  日期：——

  robust alternative method for stereochemical assignment based on 1H NMR coupling constants (31 examples) and supported by extensive DFT-based conformational analysis and calculation of 1H-1H coupling constants. DFT calculations of 13C NMR chemical shifts also cast doubt upon the role of the "γ-gauche" effect on C1 and C3 chemical shifts in trans-THβCs.

  色氨酸酯和醛的Pictet-Spengler反应已广泛应用于天然产物合成和药物化学中。迄今为止，在该反应中形成的1，3-二取代的四氢-β-咔啉（THβCs）的反式或顺式构型最常根据非对映异构体中C1和C3的13C化学位移确定。尽管反式-THβCs中的C1和C3相对于顺式-THβCs的高场位移归因于与“γ-gauche”效应相关的空间压缩，但我们表明，对于其他应受此影响的碳，该效应在实验上并未得到证实相同的压缩率。因此，我们基于1H NMR偶联常数（31个实例）开发了一种健壮的立体化学分配方法，并得到了广泛的基于DFT的构象分析和1H-1H偶联常数的计算支持。DFT对13C NMR化学位移的计算也使人们怀疑“反式”效应对反式THβCs中C1和C3化学位移的作用。
• Unexpected cis selectivity in the Pictet–Spengler reaction
  作者：Patrick D. Bailey、Mark A. Beard、Theresa R. Phillips

  DOI：10.1016/j.tetlet.2009.03.121

  日期：2009.7

  Whilst cis:trans selectivity of about 4:1 can be obtained from Pictet-Spengler reactions between tryptophan methyl esters and aldehydes using conditions of kinetic control, much higher cis selectivity (>95:5) can be obtained when both the tryptophan derivative and the aldehyde possess a Suitable pi-system: preliminary results oil the scope and limitations of this exceptional stereocontrol are presented in this Letter. (C) 2009 Elsevier Ltd. All rights reserved.