methyl (S)‐6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinoline‐3‐carboxylate | 175673-28-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (S)‐6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinoline‐3‐carboxylate
• 英文别名: (S)-methyl 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate；(S)-6,7-dimethoxy-3-methoxycarbonyl-1,2,3,4-tetrahydroisoquinoline；methyl 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate；methyl (3S)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate
• CAS: 175673-28-6
• 化学式: C₁₃H₁₇NO₄
• mdl: MFCD06618354
• 分子量: 251.282
• InChiKey: XAVYTZMVMTXAEC-JTQLQIEISA-N

物化性质

• 沸点：
  371.5±42.0 °C(Predicted)
• 密度：
  1.153±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  56.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl (S)‐6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinoline‐3‐carboxylate 在 4-二甲氨基吡啶 、 甲酸 、 硫酸 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 lithium tri-t-butoxyaluminum hydride 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 38.0h， 生成 (1R,2S,13S)-6,7,17,18-tetramethoxy-21-methyl-11,21-diazapentacyclo[11.7.1.02,11.04,9.015,20]henicosa-4,6,8,15,17,19-hexaen-12-one
  参考文献：
  名称：

  构建海洋生物生物苦素的五环核的新有效合成方法

  摘要：

  ecteinascidins的五环核是由两个基本结构单元，即1,2,3,4-四氢异喹啉衍生物和取代的苯丙氨酸衍生物，通过8个步骤，使用容易获得的L-Dopa作为起始原料构建的。关键步骤涉及上述两个结构单元的偶联，关键中间体哌嗪-1,4-二酮衍生物的11-羰基的区域选择性还原以及分子内Pictet-Spengler环化。

  DOI：

  10.1016/s0040-4039(03)01785-4
• 作为产物：
  描述：

  左旋多巴 在 盐酸 、 硫酸 、 水 、 乙酸酐 、 potassium carbonate 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 38.0h， 生成 methyl (S)‐6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinoline‐3‐carboxylate
  参考文献：
  名称：

  构建海洋生物生物苦素的五环核的新有效合成方法

  摘要：

  ecteinascidins的五环核是由两个基本结构单元，即1,2,3,4-四氢异喹啉衍生物和取代的苯丙氨酸衍生物，通过8个步骤，使用容易获得的L-Dopa作为起始原料构建的。关键步骤涉及上述两个结构单元的偶联，关键中间体哌嗪-1,4-二酮衍生物的11-羰基的区域选择性还原以及分子内Pictet-Spengler环化。

  DOI：

  10.1016/s0040-4039(03)01785-4

文献信息

• Structure and Biocatalytic Scope of Coclaurine <i>N</i> ‐Methyltransferase
  作者：Matthew R. Bennett、Mark L. Thompson、Sarah A. Shepherd、Mark S. Dunstan、Abigail J. Herbert、Duncan R. M. Smith、Victoria A. Cronin、Binuraj R. K. Menon、Colin Levy、Jason Micklefield

  DOI：10.1002/anie.201805060

  日期：2018.8.13

  plant secondary metabolites, which have been exploited to develop analgesics, antibiotics, antitumor agents, and other therapeutic agents. Biosynthesis of BIAs proceeds via a common pathway from tyrosine to (S)‐reticulene at which point the pathway diverges. Coclaurine N‐methyltransferase (CNMT) is a key enzyme in the pathway to (S)‐reticulene, installing the N‐methyl substituent that is essential for

  苄基异喹啉生物碱 (BIA) 是结构多样的植物次生代谢物家族，已被用来开发镇痛药、抗生素、抗肿瘤剂和其他治疗剂。BIA 的生物合成通过从酪氨酸到 ( S )-网状荠烯的共同途径进行，此时该途径出现分歧。椰壳碱N-甲基转移酶 (CNMT) 是 ( S )-网状荠烯途径中的关键酶，安装N-甲基取代基，这对于许多 BIA 的生物活性至关重要。在本文中，我们描述了 CNMT 的第一个晶体结构，它与诱变研究一起定义了酶活性位点的结构。还利用一系列天然和合成底物以及辅因子类似物探索了 CNMT 的特异性。这项研究的知识可用于生成生产 BIA 或合成衍生物所需的改进 CNMT 变体。
• An organogel formed from a cyclic β-aminoalcohol
  作者：Chuanqing Kang、Zheng Bian、Yabing He、Fushe Han、Xuepeng Qiu、Lianxun Gao

  DOI：10.1039/c1cc13179f

  日期：——

  A new organogelator with unique structural feature of a cyclic β-aminoalcohol is presented as the first example of gelation by aminoalcohol through hydrogen-bonding between hydroxy and amine.

  作为氨基甲醇通过羟基和胺之间的氢键作用凝胶化的第一个实例，介绍了一种具有独特结构特征的新型环δ-氨基甲醇有机凝胶剂。
• Potent direct inhibitors of factor Xa based on the tetrahydroisoquinoline scaffold
  作者：Rami A. Al-Horani、Akul Y. Mehta、Umesh R. Desai

  DOI：10.1016/j.ejmech.2012.06.032

  日期：2012.8

  Direct inhibition of coagulation factor Xa (FXa) carries significant promise for developing effective and safe anticoagulants. Although a large number of FXa inhibitors have been studied, each can be classified as either possessing a highly flexible or a rigid core scaffold. We reasoned that an intermediate level of flexibility will provide high selectivity for FXa considering that its active site is less constrained in comparison to thrombin and more constrained as compared to trypsin. We studied several core scaffolds including 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid for direct FXa inhibition. Using a genetic algorithm-based docking and scoring approach, a promising candidate 23 was identified, synthesized, and found to inhibit FXa with a K-i of 28 mu M. Optimization of derivative 23 resulted in the design of a potent dicarboxamide 47, which displayed a K-i of 135 nM. Dicarboxamide 47 displayed at least 1852-fold selectivity for FXa inhibition over other coagulation enzymes and doubled PT and aPTT of human plasma at 17.1 mu M and 20.2 mu M, respectively, which are comparable to those of clinically relevant agents. Dicarboxamide 47 is expected to serve as an excellent lead for further anticoagulant discovery. (C) 2012 Elsevier Masson SAS. All rights reserved.
• Design, syntheses, and pharmacological characterization of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3′-carboxamido)morphinan analogues as opioid receptor ligands
  作者：Yunyun Yuan、Saheem A. Zaidi、David L. Stevens、Krista L. Scoggins、Philip D. Mosier、Glen E. Kellogg、William L. Dewey、Dana E. Selley、Yan Zhang

  DOI：10.1016/j.bmc.2015.02.055

  日期：2015.4

  A series of 17-cyclopropylmethyl-3,14 beta-dihydroxy-4,5 alpha-epoxy-6 alpha-(isoquinoline-3 '-carboxamido)morphinan (NAQ) analogues were synthesized and pharmacologically characterized to study their structure-activity relationship at the mu opioid receptor (MOR). The competition binding assay showed two-atom spacer and aromatic side chain were optimal for MOR selectivity. Meanwhile, substitutions at the 1 '- and/or 4 '-position of the isoquinoline ring retained or improved MOR selectivity over the kappa opioid receptor while still possessing above 20-fold MOR selectivity over the delta opioid receptor. In contrast, substitutions at the 6 '- and/or 7 '-position of the isoquinoline ring reduced MOR selectivity as well as MOR efficacy. Among this series of ligands, compound 11 acted as an antagonist when challenged with morphine in warm-water tail immersion assay and produced less significant withdrawal symptoms compared to naltrexone in morphine-pelleted mice. Compound 11 also antagonized the intracellular Ca2+ increase induced by DAMGO. Molecular dynamics simulation studies of 11 in three opioid receptors indicated orientation of the 6 '-nitro group varied significantly in the different 'address' domains of the receptors and played a crucial role in the observed binding affinities and selectivity. Collectively, the current findings provide valuable insights for future development of NAQ-based MOR selective ligands. Published by Elsevier Ltd.
• An efficient asymmetric synthesis of allo- and pseudo-7,8-dimethoxyberbane systems through tin-mediated three component coupling
  作者：Yoshikazu Haraguchi、Sinpei Kozima、Ryohei Yamaguchi

  DOI：10.1016/0957-4166(96)00027-4

  日期：1996.2

  Three component coupling reactions of chiral 3-substituted 6,7-dimethoxy-3,4-dihydroisoquinoline with allylic tin reagents and unsaturated acid chlorides followed by intramolecular Diels-Alder reactions afford allo- and pseudo-7,8-dimethoxyberbane systems in high diastereomeric excess.