盐酸特美奎诺 | 18559-59-6

• 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
• 中文名称: 盐酸特美奎诺
• 中文别名: (S)-1,2,3,4-四氢-1-[(3,4,5-三甲氧基苯基)甲基]-6,7-异喹啉二醇盐酸盐；盐酸曲托喹芬；曲托喹酚盐酸盐一水合物
• 英文名称: (-)-Trimetoquinol hydrochloride
• 英文别名: trimetoquinol hydrochloride；(S)-(-)-trimetoquinol hydrochloride；(S)-Tetroquinol hydrochloride；l-trimetoquinol hydrochloride；trimetoquinol；(1S)-1-[(3,4,5-trimethoxyphenyl)methyl]-1,2,3,4-tetrahydroisoquinolin-2-ium-6,7-diol;chloride
• CAS: 18559-59-6
• 化学式: C₁₉H₂₃NO₅*ClH
• 分子量: 381.856
• InChiKey: UHSXRTHJCJGEKG-UQKRIMTDSA-N

物化性质

• 熔点：
  137 - 145°C
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.97
• 重原子数：
  26
• 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：
  80.2
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (S)-6,7-Bis(benzyloxy)-1-<(3,4,5-trimethoxyphenyl)methyl>-1,2,3,4-tetrahydroisoquinoline hydrochloride 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 50.0 ℃ 、405.3 kPa 条件下， 反应 16.0h， 以96%的产率得到盐酸特美奎诺
  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

文献信息

• Asymmetric Synthesis of 1-Benzyltetrahydroisoquinolines Using Chiral Oxazolo(2,3-a)tetrahydroisoquinolines.
  作者：Kunio HASHIGAKI、Keizo KAN、Nazmul QAIS、Yasuo TAKEUCHI、Masatoshi YAMATO

  DOI：10.1248/cpb.39.1126

  日期：——

  A novel synthetic route to enantiomerically pure 1-benzyltetrahydroisoquinolines (1) was developed via the reaction of oxazolo[2, 3-a]tetrahydroisoquinoline (5) with benzyltriisopropoxytitanium compounds (10). This method was applied to the synthesis of (S)-trimetoquinol (1c; a bronchodilator).

  开发了一种新颖的合成路线，用于获取对映体纯的1-苄基四氢噻嗪啉（1），该路线是通过氧杂噻唑[2, 3-a]四氢噻嗪啉（5）与苄基三异丙氧基钛化合物（10）反应实现的。该方法被应用于(S)-三美托啉（1c；一种支气管扩张剂）的合成。
• Organocatalytic Enantioselective Pictet–Spengler Approach to Biologically Relevant 1-Benzyl-1,2,3,4-Tetrahydroisoquinoline Alkaloids
  作者：Andrea Ruiz-Olalla、Martien A. Würdemann、Martin J. Wanner、Steen Ingemann、Jan H. van Maarseveen、Henk Hiemstra

  DOI：10.1021/acs.joc.5b00509

  日期：2015.5.15

  A general procedure for the synthesis of 1-benzyl-1,2,3,4-tetrahydroisoquinolines was developed, based on organocatalytic, regio- and enantioselective Pictet-Spengler reactions (86-92% ee) of N-(o-nitrophenylsulfenyl)-2-arylethyl-amines with arylacetaldehydes. The presence of the o-nitrophenylsulfenyl group, together with the MOM-protection in the catechol part of the tetrahydroisoquinoline ring system, appeared to be a productive combination. To demonstrate the versatility of this approach, 10 biologically and pharmaceutically relevant alkaloids were prepared using (R)-TRIP as the chiral catalyst: (R)-norcoclaurine, (R)-coclaurine, (R)-norreticuline, (R)-reticuline, (R)-trimemetoquinol, (R)-armepavine, (R)-norprotosinomenine, (R)-protosinomenine, (R)-laudanosine, and (R)-5-methoxylaudanosine.