trans-1-phenyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: trans-1-phenyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
• 英文别名: (1R,3S)-6,7-dihydroxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
• 化学式: C₁₆H₁₅NO₄
• 分子量: 285.299
• InChiKey: FUNISKGADRGTNM-SWLSCSKDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  89.8
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  trans-1-phenyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid 在 10% palladium on activated charcoal 、 氢气 、 potassium carbonate 、 potassium hydrogencarbonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 、 丙酮 、 乙腈 为溶剂， 生成 ((1R,3S)-6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinolin-3-yl)diphenylmethanol
  参考文献：
  名称：

  Novel tetrahydroisoquinoline based organocatalysts for asymmetric Diels–Alder reactions: insight into the catalytic mode using ROESY NMR and DFT studies

  摘要：

  For the first time an organocatalyst bearing a secondary nitrogen within a cyclohexane ring has been evaluated in the asymmetric Diels-Alder reaction. This organocatalyst is also the first of its kind based on a (1R,3S)-6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline backbone. These catalysts were tested over a range of dienes and dienophiles and displayed promising chemical conversions of up to 100% with up to 64% ee with triflic acid as the cocatalyst. Density functional theory computational studies and 20 NMR spectroscopy were used to determine the structure of the intermediate iminium ion formed between the most efficient catalyst and cinnamaldehyde. The reaction profile for each of the four possibilities in this reaction were calculated and it was found that the iminium intermediate leading to the major product is higher in energy but kinetically preferred. The activation energies of all possible reaction paths were calculated and the results correlated with the observed products. These experiments revealed that the presence of both (E)- and (Z)-isomers of the cinnamaldehyde were contributing factors for the low enantioselectivity of the reaction products. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2010.11.010
• 作为产物：
  描述：

  左旋多巴 、 苯甲醛 在 potassium carbonate 作用下， 以 乙醇 、 水 为溶剂， 生成 trans-1-phenyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
  参考文献：
  名称：

  用于不对称转移氢化反应的 C1-取代四氢异喹啉衍生物的合成与筛选

  摘要：

  四氢异喹啉 (TIQ) 衍生物表现出良好的生物活性。然而，TIQ 化合物在不对称催化中的应用是有限的。本文介绍了一系列用于不对称转移氢化 (ATH) 反应的 TIQ 衍生物。合成了手性 TIQ 氨基醇配体并筛选了芳香酮的 ATH 反应。通过实验和计算研究了 C-1 位置上的顺式和反式苯基取代对配体骨架的影响。结果表明，在室温下用 Ru 复合物获得的 TIQ 支架上的反式取向产生更高的周转率，选择性为 94% ee。顺式异构体导致没有选择性的高周转率。反式异构体在较低温度下产生 99% ee。此外，

  DOI：

  10.1002/ejoc.200901159

文献信息

• Racemic and diastereoselective synthesis of aryl and heteroaryl tetrahydroisoquinolines<i>via</i>the pictet-spengler reaction
  作者：Sylvain Aubry、Stéphane Pellet-Rostaing、Marc Lemaire、René Faure

  DOI：10.1002/jhet.5570430121

  日期：2006.1

  synthesized by the Pictet-Spengler reaction. Influence of a wide range of aryl and heteroaryl aldehydes, was investigated in the cyclization step with 3,4-dimethoxyphenylethylamine 1, L-DOPA 2 and L-3,4-dimethoxyphenylalanine methyl ester 3. Compounds 2 and 3 served as probes to assess the efficiency of two Pictet-Spengler reactions with respect to their diastereoselectivity, in order to obtain optically

  通过Pictet-Spengler反应合成了新的四氢异喹啉。在3,4-二甲氧基苯基乙胺1，L-DOPA 2和L-3,4-二甲氧基苯基丙氨酸甲酯3的环化步骤中，研究了广泛范围的芳基和杂芳基醛的影响。为了获得旋光性非对映异构体，化合物2和3用作评估两个Pictet-Spengler反应相对于其非对映选择性的效率的探针。顺式和反式-非对映异构体在短反应时间内获得，分离产率中等至良好（20-79％）。核磁共振和X射线分析均证实了预期的非对映异构体构型。
• Synthesis of tetrahydroisoquinoline (TIQ)–oxazoline ligands and their application in enantioselective Henry reactions
  作者：Rahul B. Kawthekar、Sai Kumar Chakka、Vivian Francis、Pher G. Andersson、Hendrik G. Kruger、Glenn E.M. Maguire、Thavendran Govender

  DOI：10.1016/j.tetasy.2010.04.053

  日期：2010.4

  A novel family of eleven new tetrahydroisoquinoline (TIQ)-oxazoline intermediates and five corresponding copper(II) catalysts has been developed and applied to the catalytic asymmetric Henry reaction of various aldehydes with nitromethane to provide beta-hydroxy nitroalkanes in high conversion (>99%) This paper describes the synthesis of the TIQ compounds from L-dihydroxyphenylalanine (L-DOPA) as the starting material The chiral ligands were complexed in situ with various transition metals such as Cu, Sc, Co, Zn, Ni and Mn and tested as a chiral catalyst for the Henry reaction The reaction was optimized in terms of the metal, counter ion, solvent, temperature and over a range of substrates The corresponding catalyst with copper(II) acetate and 2-propanol as the solvent provides the best enantioselectivities (up to 77% ee) of the corresponding nitroalcohol for 4-chlorobenzaldehyde (C) 2010 Elsevier Ltd All rights reserved.
• Anticancer activity of ruthenium(II) arene complexes bearing 1,2,3,4-tetrahydroisoquinoline amino alcohol ligands
  作者：Madichaba P. Chelopo、Sachin A. Pawar、Mxolisi K. Sokhela、Thavendran Govender、Hendrik G. Kruger、Glenn E.M. Maguire

  DOI：10.1016/j.ejmech.2013.05.048

  日期：2013.8

  Ruthenium complexes offer potential reduced toxicity compared to current platinum anticancer drugs. 1,2,3,4-tetrahydrisoquinoline amino alcohol ligands were synthesised, characterised and coordinated to an organometallic Ru(II) centre. These complexes were evaluated for activity against the cancer cell lines MCF-7, A549 and MDA-MB-231 as well as for toxicity in the normal cell line MDBK. They were observed to be moderately active against only the MCF-7 cells with the best IC50 value of 34 mu M for the cis-diastereomeric complex C4. They also displayed excellent selectivity by being relatively inactive against the normal MDBK cell line with SI values ranging from 2.3 to 7.4. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Novel tetrahydroisoquinoline based organocatalysts for asymmetric Diels–Alder reactions: insight into the catalytic mode using ROESY NMR and DFT studies
  作者：Tricia Naicker、Katja Petzold、Thishana Singh、Per I. Arvidsson、Hendrik G. Kruger、Glenn E.M. Maguire、Thavendran Govender

  DOI：10.1016/j.tetasy.2010.11.010

  日期：2010.12

  For the first time an organocatalyst bearing a secondary nitrogen within a cyclohexane ring has been evaluated in the asymmetric Diels-Alder reaction. This organocatalyst is also the first of its kind based on a (1R,3S)-6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline backbone. These catalysts were tested over a range of dienes and dienophiles and displayed promising chemical conversions of up to 100% with up to 64% ee with triflic acid as the cocatalyst. Density functional theory computational studies and 20 NMR spectroscopy were used to determine the structure of the intermediate iminium ion formed between the most efficient catalyst and cinnamaldehyde. The reaction profile for each of the four possibilities in this reaction were calculated and it was found that the iminium intermediate leading to the major product is higher in energy but kinetically preferred. The activation energies of all possible reaction paths were calculated and the results correlated with the observed products. These experiments revealed that the presence of both (E)- and (Z)-isomers of the cinnamaldehyde were contributing factors for the low enantioselectivity of the reaction products. (C) 2010 Elsevier Ltd. All rights reserved.
• Synthesis and Screening of C¹-Substituted Tetrahydroisoquinoline Derivatives for Asymmetric Transfer Hydrogenation Reactions
  作者：Sai Kumar Chakka、Pher G. Andersson、Glenn E. M. Maguire、Hendrik G. Kruger、Thavendran Govender

  DOI：10.1002/ejoc.200901159

  日期：2010.2

  Tetrahydroisoquinoline (TIQ) derivatives exhibit good biological activity. However, utilization of TIQ compounds in asymmetric catalysis is limited. This paper presents a series of TIQ derivatives in asymmetric transfer hydrogenation (ATH) reactions. Chiral TIQ amino alcohol ligands were synthesized and screened for the ATH reaction of aromatic ketones. The effect of a cis- and trans-phenyl substitution

  四氢异喹啉 (TIQ) 衍生物表现出良好的生物活性。然而，TIQ 化合物在不对称催化中的应用是有限的。本文介绍了一系列用于不对称转移氢化 (ATH) 反应的 TIQ 衍生物。合成了手性 TIQ 氨基醇配体并筛选了芳香酮的 ATH 反应。通过实验和计算研究了 C-1 位置上的顺式和反式苯基取代对配体骨架的影响。结果表明，在室温下用 Ru 复合物获得的 TIQ 支架上的反式取向产生更高的周转率，选择性为 94% ee。顺式异构体导致没有选择性的高周转率。反式异构体在较低温度下产生 99% ee。此外，