(Z)-2-Acetyl-1-<(3,4-dimethoxyphenyl)methylene>-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline | 17366-51-7

• 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: (Z)-2-Acetyl-1-<(3,4-dimethoxyphenyl)methylene>-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
• 英文别名: 2-acetyl-1-(3,4-dimethoxybenzylidene)-1,2,3,4-tetrahydro-6,7-dimethoxyisoquine；2-acetyl-1-(3,4-dimethoxybenzylidene)-1,2,3,4-tetrahydro-6,7-dimethoxyisoquinoline；2-acetyl-1,2,3,4-tetrahydro-6,7-dimethoxy-1-veratrylidene-isoquinoline；trans-2-acetyl-6,7-dimethoxy-1-(4,5-dimethoxybenzylidene)-1,2,3,4-tetrahydroisoquinoline；1-[(1Z)-1-[(3,4-dimethoxyphenyl)methylidene]-6,7-dimethoxy-3,4-dihydroisoquinolin-2-yl]ethanone
• CAS: 17366-51-7
• 化学式: C₂₂H₂₅NO₅
• 分子量: 383.444
• InChiKey: UKWPGQNUELVLGE-ZDLGFXPLSA-N

物化性质

• 熔点：
  192-193 °C
• 沸点：
  580.5±50.0 °C(Predicted)
• 密度：
  1.189±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  57.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (Z)-2-Acetyl-1-<(3,4-dimethoxyphenyl)methylene>-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 在 (S)-Ru(OAc)₂-BINAP 氢氧化钾 、 氢气 、 一水合肼 作用下， 以 乙醇 、 二氯甲烷 、 乙二醇 为溶剂， 24.0~170.0 ℃ 、405.3 kPa 条件下， 反应 68.0h， 生成 S-四氢罂粟碱
  参考文献：
  名称：

  General asymmetric synthesis of isoquinoline alkaloids. Enantioselective hydrogenation of enamides catalyzed by BINAP-ruthenium(II) complexes

  摘要：

  In the presence of a small amount of RuX(2)[(R)- or (S)-BINAP] (X = anionic ligand) a wide range of (Z)-2-acyl-1-benzylidene-1,2,3,4-tetrahydroisoquinolines are hydrogenated to give the saturated products in nearly quantitative yields and in high (up to 100 %) optical yields. The enamide substrates are selectively prepared by N-acylation of the corresponding 1-benzylated 3,4-dihydroisoquinolines under suitable acylation conditions; some crystalline materials having low solubility are obtained by a second-order Z/E stereomutation technique utilizing the double-bond photolability and lattice energy effects. This asymmetric hydrogenation sets the key stereogenic center in a predictable manner, either R or S flexibly, at the C(1) position of the benzylated tetrahydroisoquinolines. The chiral products are converted by standard functional group modification to tetrahydropapaverine, laudanosine, tretoquinol, norreticuline, etc. Hydrogenation of the simple 1-methylene substrate is used fbr synthesis of salsolidine. This enantioselective hydrogenation is applied to the synthesis of morphine and its artificial analogues such as morphinans and benzomorphans of either chirality. A mnemonic device is presented for predicting the reactivity and enantiofacial selection of the BINAP-Ru catalyzed hydrogenation. Reaction with BINAP-Rh catalyst proceeds with a lower enantioselectivity and an opposite sense of asymmetric induction.

  DOI：

  10.1021/jo00081a007
• 作为产物：
  描述：

  (3,4-二甲氧基苯基)乙酰氯 在 吡啶 作用下， 生成 (Z)-2-Acetyl-1-<(3,4-dimethoxyphenyl)methylene>-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  1-甲基-1,2,3,4-四氢萘并[2,1- f ]异喹啉的总合成涉及氢化三丁基锡（IV）引起的自由基环化

  摘要：

  我们描述了基于自由基环化的1-甲基-1,2,3,4-四氢萘并[1,2- f ]异喹啉的两个总合成。其中之一包括将N- {2- [2-（2-溴苯基）-1-甲氧基乙基]苯基乙基}乙酰胺环化，然后转化所得的N- [2-（10-甲氧基-9,10-二氢- 1-菲基）乙基]乙酰胺。第二种方法是基于已知的将1-（2-溴苄基）异色满-3-酮环化为4,5,6a，7-四氢二苯并[ de，g ]色满-3-酮，然后转化所得的2-（ 1-菲基）乙酰胺。

  DOI：

  10.1016/s0040-4020(01)00040-0

文献信息

• Piperazine derivatives
  申请人：Daiichi Pharmaceutical Co., Ltd.

  公开号：US05681954A1

  公开（公告）日：1997-10-28

  A compound represented by formula (I): ##STR1## wherein Q represents an aryl group, a heterocyclic group, a diarylmethyl group, an aralkyl group composed of an aryl group and an alkylene group, an alkyl group or a cycloalkyl group, in which the aryl group, heterocyclic group, and the aryl moiety of the diarylmethyl group and aralkyl group may be substituted with one or more substituents; R represents a bicyclic, substituted, nitrogen-containing heterocyclic group or a substituted phenyl group, in which the nitrogen-containing heterocyclic group is composed of a 5-membered, substituted, aromatic or saturated ring containing one or two nitrogen atoms and a 6-membered ring; and Z represents an alkylene group, an alkenylene group, an alkylene group, a carbonyl group, an alkylene group containing a carbonyl group or an oxalyl group, or a salt thereof. The compound has calmodulin inhibitory activity and is useful as a treating agent for diseases in the circulatory organs or in the cerebral region which are caused by excessive activation of calmodulin.

  一种由化学式(I)表示的化合物：##STR1## 其中Q代表芳基、杂环基、二芳基甲基基、芳基和烷基组成的芳基烷基基团、烷基或环烷基，其中芳基、杂环基、二芳基甲基基和芳基烷基基团中的芳基可被一个或多个取代基取代；R代表双环取代的含氮杂环基或取代的苯基，其中含氮杂环基由一个含有一个或两个氮原子的5元取代芳香或饱和环和一个6元环组成；Z代表烷基、烯烃基、烷基、羰基、含有羰基的烷基或草酸基，或其盐。该化合物具有钙调蛋白抑制活性，并可用作治疗因钙调蛋白过度活化引起的循环器官或脑区疾病的治疗剂。
• Process for preparing N-acyltetrahydroisoquinoline
  申请人：Takasago Perfumery Co., Ltd.

  公开号：EP0245960A2

  公开（公告）日：1987-11-19

  A process for preparing an N-acyltetrahydro­isoquinoline represented by formula (II) wherein A repesents a phenylene ring substituted with a hydroxyl group, a Cl-4 alkoxy, acetoxy, or benzyloxy group; R represents a hydrogen atom, a Cl-1 alkyl, or phenyl group; and X represents a hydrogen atom, a phenyl group, or a phenyl group substituted with a hydroxyl group, a lower alkoxy group or an acetoxy group, which comprises asymmetrically hydrogenating a solution of an N-acyl-1-­methylenetetrahydroisoquinoline or N-acyl-1-benzylidene­tetrahydroisoquinoline represented by formula (I) wherein A, R, and X are as defined above, in solution at a H₂ pressure of 1 to 10 kg/cm² at 10 to 40°C for 10 to 160 hours, in the presence as catalyst of an optically active ruthenium-phosphine complex, of which several examples are given. The process exclusively and efficiently provides a useful isomer of the N-actyltetrahydroisoquinoline of high purity which is useful as an intermediate for synthesizing isoquinoline type alkaloids as pharmaceuticals without involving optical resolution of a racemate.

  一种制备由式(II)代表的N-酰基四氢异喹啉的工艺 其中 A 代表被羟基、Cl-4 烷氧基、乙酰氧基或苄氧基取代的苯基环；R 代表氢原子、Cl-1 烷基或苯基；X 代表氢原子、苯基或被羟基、低级烷氧基或乙酰氧基取代的苯基、 其中包括不对称地氢化由式（I）代表的 N-酰基-1-亚甲基四氢异喹啉或 N-酰基-1-亚苄基四氢异喹啉的溶液 其中 A、R 和 X 如上定义，在光学活性钌膦络合物作为催化剂存在下，于 10 至 40°C 下，在 1 至 10 kg/cm² 的 H₂ 压力下，在溶液中进行 10 至 160 小时。 该工艺独家有效地提供了一种有用的高纯度 N-内酰四氢异喹啉异构体，该异构体可用作合成异喹啉类生物碱的中间体，而不涉及外消旋体的光学解析。
• Piperazine derivatives useful as calmodolin inhibitors
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP0624584A1

  公开（公告）日：1994-11-17

  A compound represented by formula (I): wherein Q represents an aryl group, a heterocyclic group, a diarylmethyl group, an aralkyl group composed of an aryl group and an alkylene group, an alkyl group or a cycloalkyl group, in which the aryl group, heterocyclic group, and the aryl moiety of the diarylmethyl group and aralkyl group may be substituted with one or more substituents; R represents a bicyclic, substituted, nitrogen-containing heterocyclic group or a substituted phenyl group, in which the nitrogen-containing heterocyclic group is composed of a 5-membered, substituted, aromatic or saturated ring containing one or two nitrogen atoms and a 6-membered ring; and Z represents an alkylene group, an alkenylene group, an alkylene group, a carbonyl group, an alkylene group containing a carbonyl group or an oxalyl group, or a salt thereof. The compound has calmodulin inhibitory activity and is useful as a treating agent for diseases in the circulatory organs or in the cerebral region which are caused by excessive activation of calmodulin.

  式 (I) 所代表的化合物： 其中 Q 代表芳基、杂环基、二芳甲基、由芳基和亚烷基组成的芳烷基、烷基或环 烷基，其中芳基、杂环基以及二芳甲基和芳烷基的芳基可被一个或多个取代基取代；R 代表双环、取代的含氮杂环基团或取代的苯基，其中含氮杂环基团由含有一个或两个氮原子的五元环、取代的芳香环或饱和环以及六元环组成；以及 Z 代表烯基、烯基、亚烷基、羰基、含有羰基的亚烷基或草酰基、 或其盐。该化合物具有钙调蛋白抑制活性，可用于治疗因钙调蛋白过度活化而引起的循环器官或脑部疾病。
• Asymmetric synthesis of isoquinoline alkaloids by homogeneous catalysis
  作者：Ryoji. Noyori、Masako. Ohta、Yi. Hsiao、Masato. Kitamura、Tetsuo. Ohta、Hidemasa. Takaya

  DOI：10.1021/ja00282a054

  日期：1986.10
• Piperazine derivatives useful as calmodulin inhibitors
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP0624584B1

  公开（公告）日：1998-08-19