(R)-1-(4'-methoxybenzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline | 60383-76-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: (R)-1-(4'-methoxybenzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
• 英文别名: (+)-(R)-O,O-dimethylcoclaurine；(R)-(+)-O,O-dimethyloclaurine；(R)-6,7-dimethoxy-1-(para-methoxyphenylmethyl)-1,2,3,4-tetrahydroisoquinoline；(R)-6,7-dimethoxy-1-(p-methoxyphenylmethyl)-1,2,3,4-tetrahydroisoquinoline；(1R)-6,7-dimethoxy-1-[(4-methoxyphenyl)methyl]-1,2,3,4-tetrahydroisoquinoline
• CAS: 60383-76-8
• 化学式: C₁₉H₂₃NO₃
• 分子量: 313.397
• InChiKey: GXTUEUWFEKEQHJ-QGZVFWFLSA-N

物化性质

• 沸点：
  454.0±45.0 °C(Predicted)
• 密度：
  1.108±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  39.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-1-(4'-methoxybenzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 在 氢溴酸 作用下， 以 水 、 溶剂黄146 为溶剂， 反应 0.02h， 以70%的产率得到(R)-6,7-dimethoxy-l-(p-methoxyphenylmethyl)-1,2,3,4-tetrahydroisoquinoline hydrobromide
  参考文献：
  名称：

  [EN] NOVEL ENANTIOMERS OF TETRAHYDROISOQUINOLINE DERIVATIVES AND THEIR PHARMACEUTICALLY ACCEPTABLE SALTS, THEIR PREPARATIONS AND PHARMACEUTICAL COMPOSITIONS
  [FR] NOUVEAUX ENANTIOMERES DE DERIVES DE TETRAHYDROISOQUINOLINE ET LEURS SELS PHARMACEUTIQUEMENT ACCEPTABLES, PREPARATIONS ET COMPOSITIONS PHARMACEUTIQUES DE CES DERNIERS

  摘要：

  该披露涉及四氢异喹啉衍生物的新对映体及其药用盐，它们的制备和药物组合物。所提供的四氢异喹啉衍生物的对映体在刺激心率和降压活性、抑制血小板聚集活性以及对诱导型NO合酶的抑制方面具有用途。四氢异喹啉衍生物的对映体及其药用盐对治疗充血性心力衰竭、高血压、血栓形成、炎症、败血症、心脏功能不全和播散性血管内凝血症具有有效性。

  公开号：

  WO2003095426A1
• 作为产物：
  描述：

  6,7-dimethoxy-1-(4-methoxybenzyl)-3,4-dihydroisoquinoline 在 (S,S)-Noyori's catalyst 甲酸 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以60.9 mg的产率得到(R)-1-(4'-methoxybenzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  通过 α-氨基腈的烷基化合成 (-)-(S)-去甲月桂苷、(+)-(R)-O,O-二甲基椰油碱和 (+)-(R)-Salsolidine

  摘要：

  1-取代的 1,2,3,4-四氢异喹啉生物碱的短不对称合成描述了通过未保护的 α-氨基腈的去质子化和所得碳负离子的烷基化，然后自发消除 HCN 和不对称还原。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

  DOI：

  10.1002/ejoc.200700261

文献信息

• Practical Metal-Free C(sp³)H Functionalization: Construction of Structurally Diverse α-Substituted<i>N</i>-Benzyl and<i>N</i>-Allyl Carbamates
  作者：Zhiyu Xie、Lei Liu、Wenfang Chen、Hongbo Zheng、Qingqing Xu、Huiqing Yuan、Hongxiang Lou

  DOI：10.1002/anie.201310193

  日期：2014.4.7

  is a practical and universal CH functionalization of readily removable N‐benzyl and N‐allyl carbamates, with a wide range of nucleophiles at ambient temperature promoted by Ph3CClO4. The metal‐free reaction has an excellent functional‐group tolerance, and displays a broad scope with respect to both N‐carbamates and nucleophile partners (a variety of organoboranes and CH compounds). The synthetic utility

  描述了一种实用的和普遍Ç 易于除去h的官能ñ -苄基和Ñ -烯丙基氨基甲酸酯，在环境温度下的宽范围的亲核试剂通过pH促进3 CClO 4。无金属反应具有出色的官能团耐受性，并且在N-氨基甲酸酯和亲核试剂（各种有机硼烷和CH化合物）方面都具有广阔的应用范围。展示了目标以及面向多样性的综合中的综合效用。
• A Novel Straightforward Synthesis of Enantiopure Tetrahydroisoquinoline Alkaloids
  作者：Rafael Pedrosa、Celia Andrés、Jesús M. Iglesias

  DOI：10.1021/jo001397s

  日期：2001.1.1

  formation of chiral 2,3-substituted perhydro-1,3-benzoxazines derived from (-)-8-aminomenthol, (ii) diastereoselective intramolecular ring opening of the N,O-acetal moiety by an arylmetal generated from the substituent at the nitrogen atom in the perhydrobenzoxazine ring, and (iii) removal of the chiral auxiliary appendage. The starting perhydrobenzoxazines are easily prepared from (-)-8-aminomenthol and two

  描述了一种对映纯的1-取代的四氢异喹啉（THIQ）的新颖，直接，高产的立体选择性方法。在THIQ核形成过程中建立立体中心的成功方法是基于（i）形成衍生自（-）-8-氨基薄荷醇的手性2,3-取代的过氢-1,3-苯并恶嗪，（ii）非对映选择性N，O-乙缩醛部分的分子内开环是由在全氢苯并恶嗪环中氮原子上的取代基产生的芳基金属引起的，和（iii）除去手性辅助附属物。起始的全氢苯并恶嗪很容易由（-）-8-氨基薄荷醇和两种不同的醛制备，并且分子内的开口具有立体特异性，从而形成单一的立体异构体。该方法可以制备多种对映体1取代的THIQ，
• METHOD FOR RESOLVING ENANTIOMERS FROM RACEMIC MIXTURE HAVING CHIRAL CARBON IN ALPHA POSITION OF NITROGEN
  申请人：Ahn Soon Kil

  公开号：US20090036679A1

  公开（公告）日：2009-02-05

  Disclosed relates to a simplified method for resolving enantiomers by dissolving a racemic mixture having chiral carbon in α-position of nitrogen and an amino acid to prepare a diastereomeric salt, not using catalyses or enzymes, with enhancing the optical purity remarkably. Moreover, the present invention can prepare the enantiomers in large quantities without using expensive catalysts or without controlling the reaction conditions for the activity of enzymes applied.

  揭示了一种简化的方法，通过将含有手性碳的混合物溶解在氮的α位和氨基酸中，制备出对映异构盐来分离对映体，而不使用催化剂或酶，显著提高光学纯度。此外，本发明可以大量制备对映体，而无需使用昂贵的催化剂或控制应用酶的反应条件。
• Novel enantiomers of etrahydroisoquinoline derivatives and theirpharmaceutically acceptable salts, their preparations and pharmaceutical compositions
  申请人：Yun-Choi Hye-Sook

  公开号：US20060058346A1

  公开（公告）日：2006-03-16

  The disclosure concerns novel enantiomers of tetrahydroisoquinoline derivatives and their pharmaceutically acceptable salts, their preparations and pharmaceutical compositions. The enantiomers of tetrahydroisoquinoline derivatives are provided which are useful in stimulating heart rate and hypotensive activity, inhibitory activity against platelet aggregation, and suppressive against inducible NO synthase. The enantiomers of tetrahydroisoquinoline derivatives and their pharmaceutically acceptable salts are effective for treating congestive heart failure, hypertension, thrombosis, inflammation, septicemia, cardiac insufficiency, and disseminated intravascular coagulopathy.

  该披露涉及四氢异喹啉衍生物的新手性异构体及其药学上可接受的盐、其制备和制药组合物。提供了四氢异喹啉衍生物的手性异构体，其对于刺激心率和降压活性、抑制血小板聚集活性以及对可诱导的一氧化氮合酶具有抑制作用是有用的。四氢异喹啉衍生物的手性异构体及其药学上可接受的盐对于治疗充血性心力衰竭、高血压、血栓形成、炎症、败血症、心脏功能不全和弥漫性血管内凝血是有效的。
• Enantioselective synthesis of (R)-(+)- and (S)-(−)-higenamine and their analogues with effects on platelet aggregation and experimental animal model of disseminated intravascular coagulation
  作者：Mi Kyung Pyo、Duck-Hyung Lee、Doo-Hyun Kim、Ji-Hye Lee、Jong-Cheon Moon、Ki Churl Chang、Hye Sook Yun-Choi

  DOI：10.1016/j.bmcl.2008.05.094

  日期：2008.7

  Optically active tetrahydroisoquinoline alkaloids, (R)-(+)-higenamine (1R) and (S)-(-)-higenamine (1 S), and their optically active 1-naphthylmethyl analogues (2 and 3), were synthesized by enantioselective hydrogenation of the corresponding dihydroisoquinoline intermediates 7 as a key step. The evaluation of the platelet anti-aggregation effect demonstrated clearly that the (S)-(-)-enantiomers, 1S, 2S, and 3S, had higher inhibitory potency than the corresponding (R)-(+)-antipodes, 1R, 2R, and 3R, respectively, to platelet aggregation induced by epinephrine. 1S enantiomer was superior to the corresponding 1R enantiomer in attenuating all of the disseminated intravascular coagulation (DIC) and multiple organ failure (MOF) parameters tested, while the S enantiomers 2S and 3S ameliorated some of the DIC and MOF parameters more effectively than the corresponding antipodes 2R and 3R. (c) 2008 Published by Elsevier Ltd.