(1R-trans)-1,2,3,4-tetrahydro-5-iodo-1,3-dimethyl-6,8-bis(phenylmethoxy)-2-(phenylmethyl)isoquinoline | 160538-96-5

• 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: (1R-trans)-1,2,3,4-tetrahydro-5-iodo-1,3-dimethyl-6,8-bis(phenylmethoxy)-2-(phenylmethyl)isoquinoline
• 英文别名: (1R,3R)-2-benzyl-5-iodo-1,3-dimethyl-6,8-bis(phenylmethoxy)-3,4-dihydro-1H-isoquinoline
• CAS: 160538-96-5
• 化学式: C₃₂H₃₂INO₂
• 分子量: 589.516
• InChiKey: HDUUHRGXUZTYMC-DNQXCXABSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  21.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1R-trans)-1,2,3,4-tetrahydro-5-iodo-1,3-dimethyl-6,8-bis(phenylmethoxy)-2-(phenylmethyl)isoquinoline 在 四(三苯基膦)钯 盐酸 、 碳酸氢钠 作用下， 以 甲醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 36.0h， 生成 4-[(R(a),1R,3R)-2-phenylmethyl-6,8-bis-phenylmethoxy-1,3-dimethyl-1,2,3,4-tetrahydroisoquinolin-5-yl]-8-methoxy-6-methylnaphthalen-1-ol
  参考文献：
  名称：

  Total Synthesis of Michellamines A−C, Korupensamines A−D, and Ancistrobrevine B

  摘要：

  Efficient syntheses of the title compounds have been developed. Several strategies for preparation of each of the naphthalene and tetrahydroisoquinoline (THIQ) portions were developed. Initial attempts to use benzyne plus furan cycloaddition reactions were thwarted by the unfavorable sense of the regiochemical outcome. An interesting annulation reaction of benzynes derived from 2,4-dibromophenol derivatives formed the core of the shortest naphthalene synthesis. An alternative annulation initiated by the addition of a benzylic sulfone anion to methyl crotonate led to an efficient naphthol synthesis amenable to large scale. The THIQ synthesis of Bringmann was used initially and subsequently complemented by a route whose key step involved the opening of N-tosyl-2-methylethyleneimine by a 3,5-dimethoxyphenylcuprate reagent. The results from a variety of aryl cross-coupling reactions are described. Suzuki coupling of the boronic acid derived from the naphthalene moiety with a THIQ-iodide was the most generally effective method for forming the hindered biaryl bond. The korupensamines and ancistrobrevine B were then revealed by deprotection. The oxidative coupling of several 4-aryl-1-naphthols to indigoids (cross ring naphthoquinones) with silver oxide effected the critical dimerization reaction needed to establish the michellamine skeleton. For the perbenzylated precursor, hydrogen over palladium on carbon both reductively bleached the indigoid and hydrogenolyzed the benzyl ethers and amines to release the free michellamines. The synthesis of several michellamine analogues, including ent-michellamines, is outlined. Results of anti-HIV assays are presented.

  DOI：

  10.1021/jo9908187
• 作为产物：
  描述：

  (1R,3R)-2-benzyl-6,8-dimethoxy-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline 在 氢溴酸 、 碘 、 silver sulfate 、 sodium iodide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 (1R-trans)-1,2,3,4-tetrahydro-5-iodo-1,3-dimethyl-6,8-bis(phenylmethoxy)-2-(phenylmethyl)isoquinoline
  参考文献：
  名称：

  甲胺苯丙胺C和顺牛膝B的总合成

  摘要：

  首次完成了科鲁苯胺C（3）和antrotrobrevine B（4）的首次合成。描述了与萘部分的构造，四氢异喹啉单元上甲氧基的操纵以及受阻联芳基的形成有关的重要的苯炔化学。

  DOI：

  10.1016/0040-4039(96)00525-4

文献信息

• Stille coupling of thiophene with a tetrahydroisoquinoline alkaloid
  作者：S. Abdel-Sattar、Hamad Elgazwy

  DOI：10.1070/mc2006v016n02abeh002242

  日期：2006.1

  The Stille coupling of tributylstannylthiophenes with halogenated tetrahydroisoquinolines produces analogues of michellamine alkaloids

  三丁基锡烷基噻吩与卤代四氢异喹啉的斯蒂勒偶联产生了米切尔敏生物碱的类似物
• Synthetic analogs of dioncophylline and michellamines by stille coupling
  作者：Abdel-Sattar S. Hamad Elgazwy

  DOI：10.1002/jhet.5570430503

  日期：2006.9

  Dioncophielline and Michellamine Analogs S-5, R-5, S-7, R-7, S,S-8, R,R-8 and R,S-8 were synthesized by using Stille coupling condition (Pd°-mediated cross coupling) proceeds in low yield when using stannanes 1 or 2 with tetrahydroisoquinolinyl bromide 3. The addition of tetrahydroisoquinolinyl iodide 4 instead of 3 significantly improves the efficiency of the coupling and providing a variety of Dioncophielline

  Dillecophielline和Michellamine类似物S-5，R-5，S-7，R-7，S，S-8，R，R-8和R，S-8是通过Stille偶联条件合成的（Pd°介导的交叉当将锡烷1或2与四氢异喹啉基溴3一起使用时，收率低。加入四氢异喹啉基碘化物4而不是3可以显着提高偶联效率，并以中等收率提供各种Dioncophielline和Michellamine类似物。
• Total synthesis of Michellamines A-C: Important anti-HIV agents
  作者：Thomas R. Hoye、Minzhang Chen、Liang Mi、Owen P. Priest

  DOI：10.1016/s0040-4039(00)78487-5

  日期：1994.11

  Michellamines A-C have been prepared by total synthesis in 7 and 16 linear steps from known and commercial materials, respectively. Key steps include i) palladium(0)-mediated biaryl coupling, ii) silver oxide promoted oxidative 1-naphthol coupling to an atropisomeric mixture of cross-ring quinones (indigoids), and iii) simultaneous per-debenzylation/reductive bleaching to the central 2,2'-binaphthol.
• Studies of Palladium-Catalyzed Cross-Coupling Reactions for Preparation of Highly Hindered Biaryls Relevant to the Korupensamine/Michellamine Problem
  作者：Thomas R. Hoye、Minzhang Chen

  DOI：10.1021/jo960882d

  日期：1996.1.1