(+/-)-1-(3-hydroxy-4-methoxybenzyl)-1,2,3,4-tetrahydro-2-methyl-6,7-methylenedioxyisoquinoline | 109741-34-6

• 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: (+/-)-1-(3-hydroxy-4-methoxybenzyl)-1,2,3,4-tetrahydro-2-methyl-6,7-methylenedioxyisoquinoline
• 英文别名: (±)-2-methoxy-5-((6-methyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinolin-5-yl)methyl)phenol；2-methoxy-5-(6-methyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinolin-5-ylmethyl)-phenol；2-Methoxy-5-(6-methyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isochinolin-5-ylmethyl)-phenol；1-(3-Hydroxy-4-methoxybenzyl)-2-methyl-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoline；2-methoxy-5-[(6-methyl-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isoquinolin-5-yl)methyl]phenol
• CAS: 109741-34-6
• 化学式: C₁₉H₂₁NO₄
• 分子量: 327.38
• InChiKey: LZDZXNMXZLWRLZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (+/-)-1-(3-hydroxy-4-methoxybenzyl)-1,2,3,4-tetrahydro-2-methyl-6,7-methylenedioxyisoquinoline 在 氢氧化钾 、 硫酸 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 反应 48.52h， 生成 dicentrine
  参考文献：
  名称：

  Studies on tetrahydroisoquinolines. XXVIII Syntheses of (.+-.)-N-methyllaurotetanine, (.+-.)-cassythicine, (.+-.)-9-hydroxy-1,2,3,10-tetramethoxyaporphine, (.+-.)-dicentrine, and (.+-.)-thalicsimidine.

  摘要：

  标题的非典型生物碱骨架是通过对1-(3-羟基-4-甲氧基苄基)-1, 2, 3, 4-四氢异喹啉进行铅四乙酸盐氧化合成的。

  DOI：

  10.1248/cpb.34.1946
• 作为产物：
  描述：

  (3-苄氧基-4-甲氧基-苯基)乙酸 在 甲烷 、 palladium dichloride sodium tetrahydroborate 、 氢气 、 三氯氧磷 作用下， 以 甲醇 、 氯仿 、 甲苯 、 xylene 为溶剂， 25.0 ℃ 、344.73 kPa 条件下， 反应 25.2h， 生成 (+/-)-1-(3-hydroxy-4-methoxybenzyl)-1,2,3,4-tetrahydro-2-methyl-6,7-methylenedioxyisoquinoline
  参考文献：
  名称：

  Synthesis of some 1-(3-hydroxy-4-methoxybenzyl)-2-alkyl-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinolines and their binding affinities to DA receptor subtypes

  摘要：

  1-(3-Hydroxy-4-methoxybenzyl)-2-alkyl-6,7-methylenedioxytetrahydroisoquinolines (3a-c), derived from the D-1 selective antagonist S-bulbocapnine by cleavage of the bond between the 2 aromatic moieties, have been synthesized and their in vitro affinity towards D-1 and D-2 receptors evaluated. Of the compounds tested, the 2-methyl derivative 3a while showing poor affinity towards D-1 receptors was able to inhibit the D-2 radioligand H-3-raclopride binding by 60% at 10(-5) M. Conformational analysis allows reasonable explanations of the loss of D-1-affinity of 3a with respect to the model.

  DOI：

  10.1016/0223-5234(94)90126-0

文献信息

• The ethoxycarbonyl group as both activating and protective group in <i>N</i>-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids
  作者：Marco Keller、Karl Sauvageot-Witzku、Franz Geisslinger、Nicole Urban、Michael Schaefer、Karin Bartel、Franz Bracher

  DOI：10.3762/bjoc.17.183

  日期：——

  We present a systematic investigation on an improved variant of the N-acyl-Pictet–Spengler condensation for the synthesis of 1-benzyltetrahydroisoquinolines, based on our recently published synthesis of N-methylcoclaurine, exemplified by the total syntheses of 10 alkaloids in racemic form. Major advantages are a) using ω-methoxystyrenes as convenient alternatives to arylacetaldehydes, and b) using

  我们基于我们最近发表的N-甲基椰壳碱的合成，以 10 种外消旋形式的生物碱的全合成为例，对用于合成 1-苄基四氢异喹啉的N-酰基-Pictet-Spengler 缩合的改进变体进行了系统研究。主要优点是a)使用ω-甲氧基苯乙烯作为芳基乙醛的方便替代品，b)使用乙氧基羰基残基来活化环化反应的芳基乙胺前体，并且作为显着的扩展，也作为酚残基的保护基团。闭环后，乙氧羰基保护的酚类在氨基甲酸酯基团进一步加工的同时脱保护，或者按照路线A（铝氢化锂还原）得到N-甲基化酚产物，或者按照路线B（用过量甲基锂处理）得到N-甲基化酚产物。相应的具有游离N-H功能的生物碱。乙氧基羰基的双重使用显着缩短了羟基化1-苄基四氢异喹啉的合成路线。毫不奇怪，这十种生物碱对 TPC2 阳离子通道和肿瘤细胞系 VCR-R CEM 没有表现出显着的作用，并且没有表现出 P-糖蛋白阻断活性。但由于其游离酚基团，根据该化学型结构-活
• Kikkawa, Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1959, vol. 79, p. 1244,1247
  作者：Kikkawa

  DOI：——

  日期：——
• Studies on tetrahydroisoquinolines. XXVIII Syntheses of (.+-.)-N-methyllaurotetanine, (.+-.)-cassythicine, (.+-.)-9-hydroxy-1,2,3,10-tetramethoxyaporphine, (.+-.)-dicentrine, and (.+-.)-thalicsimidine.
  作者：HIROSHI HARA、FUMIAKI HASHIMOTO、OSAMU HOSINO、BUNNSUKE UMEZAWA

  DOI：10.1248/cpb.34.1946

  日期：——

  The skeleton of the title aporphines was synthesized by use of the lead tetraacetate oxidation of 1-(3-hydroxy-4-methoxybenzyl)-1, 2, 3, 4-tetrahydroisoquinolines.

  标题的非典型生物碱骨架是通过对1-(3-羟基-4-甲氧基苄基)-1, 2, 3, 4-四氢异喹啉进行铅四乙酸盐氧化合成的。
• Synthesis of some 1-(3-hydroxy-4-methoxybenzyl)-2-alkyl-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinolines and their binding affinities to DA receptor subtypes
  作者：GA Pinna、G Cignarella、S Scolastico、ML Porceddu

  DOI：10.1016/0223-5234(94)90126-0

  日期：1994.1

  1-(3-Hydroxy-4-methoxybenzyl)-2-alkyl-6,7-methylenedioxytetrahydroisoquinolines (3a-c), derived from the D-1 selective antagonist S-bulbocapnine by cleavage of the bond between the 2 aromatic moieties, have been synthesized and their in vitro affinity towards D-1 and D-2 receptors evaluated. Of the compounds tested, the 2-methyl derivative 3a while showing poor affinity towards D-1 receptors was able to inhibit the D-2 radioligand H-3-raclopride binding by 60% at 10(-5) M. Conformational analysis allows reasonable explanations of the loss of D-1-affinity of 3a with respect to the model.