(S)-(-)-(3-methoxybenzyl)-1,2,3,4-tetrahydroisoquinoline | 136657-32-4

• 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: (S)-(-)-(3-methoxybenzyl)-1,2,3,4-tetrahydroisoquinoline
• 英文别名: (1S)-6,7-dimethoxy-1-[(3-methoxyphenyl)methyl]-1,2,3,4-tetrahydroisoquinoline
• CAS: 136657-32-4
• 化学式: C₁₉H₂₃NO₃
• 分子量: 313.397
• InChiKey: NRJCAOCPBSXOGP-KRWDZBQOSA-N

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：

  (S)-(-)-(3-methoxybenzyl)-1,2,3,4-tetrahydroisoquinoline 在 草酰氯 、 氨 、 水 、 sodium 、 sodium cyanoborohydride 、 溶剂黄146 、 二甲基亚砜 、 三乙胺 、 叔丁醇 作用下， 以 溶剂黄146 为溶剂， 反应 29.67h， 生成 (S)-(-)-2,3-dimethoxy-5,6,8,8a,9,10,13,13a-octahydro-11H-dibenzoquinolizin-1-one
  参考文献：
  名称：

  Asymmetric synthesis of benzoquinolizidines: a formal synthesis of (-)-emetine

  摘要：

  Chiral formamidines affixed to tetrahydroisoquinoline derivatives affords the appropriate precursor 9 to various benzo[a]quinolizidines 2 and 3 and dibenzo[a,g]quinolizidines 4 in modest to high optical purity. Both 3 and 4 have been utilized in total syntheses of natural emetine 1, thus the route herein constitutes a formal total synthesis of 1. Furthermore, Mannich cyclizations of 1-alkylisoquinolines 18a-c proceeded with or without loss of absolute stereochemistry at the C-1 position. Explanation for this behavior is based upon whether a [3,3] rearrangement or a Mannich reaction takes place. The former results in virtually complete racemization of 18, whereas the latter totally conserves the chirality in 18. Finally, 1-alkynylisoquinolines of high optical purity were transformed, via the Overman protocol, to alkylidine benzo[a]quinolizidines 24 in good yield and to our knowledge, high enantiomeric excess.

  DOI：

  10.1021/jo00024a032
• 作为产物：
  描述：

  N-(2-(3,4-二甲氧基苯基)乙基)-2-(3-甲氧基苯基)乙酰胺 在 甲酸 、 (S,S)-N-(对甲苯磺酰)-1,2-二苯乙烷二胺(对异丙基苯)氯化钌(II) 、 三乙胺 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 10.5h， 生成 (S)-(-)-(3-methoxybenzyl)-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Design, synthesis, and pharmacological evaluation of novel tetrahydroprotoberberine derivatives: Selective inhibitors of dopamine D1 receptor

  摘要：

  A series of new tetrahydroprotoberberine (THPB) derivatives were designed, synthesized, and tested for their binding affinity towards dopamine (D-1 and D-2) and serotonin (5-HT1A and 5-HT2A) receptors. Many of the THPB compounds exhibited high binding affinity and activity at the dopamine D-1 receptor, as well as high selectivity for the D-1 receptor over the D-2, 5-HT1A, and 5-HT2A receptors. Among these, compound 19c exhibited a promising D-1 receptor binding affinity (K-i = 2.53 nM) and remarkable selectivity versus D2R (inhibition = 81.87%), 5-HT1AR (inhibition = 61.70%), and 5-HT2AR (inhibition = 24.96%). Compared with l-(S)-stepholidine (l-SPD) (D-1 K-i = 6.23 nM, D-2 K-i = 56.17 nM), compound 19c showed better binding affinity for the D-1 receptor (2.5-fold higher) and excellent D-2/D-1 selectivity. Functional assays found compounds 18j, 18k, and 19c are pure D-1 receptor antagonists. These results indicate that removing the C10 hydroxy group and introducing a methoxy group at C11 of the pharmacophore of l-SPD can reverse the function of THPB compounds at the D-1 receptor. These results are in accord with molecular docking studies. Crown Copyright (C) 2012 Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.05.057