(1R-trans)-5-bromo-1,2,3,4-tetrahydro-1,3-dimethyl-6,8-bis(phenylmethoxy)-2-(phenylmethyl)isoquinoline | 160466-01-3

• 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)-5-bromo-1,2,3,4-tetrahydro-1,3-dimethyl-6,8-bis(phenylmethoxy)-2-(phenylmethyl)isoquinoline
• 英文别名: (1R,3R)-2-benzyl-5-bromo-1,3-dimethyl-6,8-bis(phenylmethoxy)-3,4-dihydro-1H-isoquinoline
• CAS: 160466-01-3
• 化学式: C₃₂H₃₂BrNO₂
• 分子量: 542.516
• InChiKey: LGJULTQHCQWVHQ-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)-5-bromo-1,2,3,4-tetrahydro-1,3-dimethyl-6,8-bis(phenylmethoxy)-2-(phenylmethyl)isoquinoline 在 四(三苯基膦)钯 barium dihydroxide 、 溶剂黄146 、 pyridinium hydrobromide perbromide 作用下， 以 氯仿 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 65.0h， 生成 (1R,3R)-2-Benzyl-6,8-bis-benzyloxy-5-(4-benzyloxy-3-bromo-5-methoxy-7-methyl-naphthalen-1-yl)-1,3-dimethyl-1,2,3,4-tetrahydro-isoquinoline
  参考文献：
  名称：

  The first stereospecific synthesis of michellamine B

  摘要：

  二聚生物碱小檗胺 B 是通过钯催化四苄基化的 korupensmine A 衍生物的 6′-萘硼酸与四苄基化的 korupensmine B 衍生物的 6′-溴类似物的交叉偶联而合成的。

  DOI：

  10.1039/cc9960000923
• 作为产物：
  描述：

  (1R,3R)-2-Benzyl-8-methoxy-1,3-dimethyl-1,2,3,4-tetrahydro-isoquinolin-6-ol 在 sodium hydroxide 、 溴 、 苄基三丁基氯化铵 、 sodium hydride 、 异丙硫醇 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 (1R-trans)-5-bromo-1,2,3,4-tetrahydro-1,3-dimethyl-6,8-bis(phenylmethoxy)-2-(phenylmethyl)isoquinoline
  参考文献：
  名称：

  Bringmann, Gerhard; Goetz, Roland; Harmsen, Sven, Liebigs Annalen, 1996, # 12, p. 2045 - 2058

  摘要：

  DOI：

文献信息

• The synthesis and biological activity of two analogs of the anti-HIV alkaloid michellamine B
  作者：Velaparthi Upender、Daniel J. Pollart、Jyanwei Liu、Peter D. Hobbs、Cris Olsen、Wan-Ru Chao、Bonnie Bowden、Jac L. Crase、David W. Thomas、Anjali Pandey、John A. Lawson、Marcia I. Dawson

  DOI：10.1002/jhet.5570330460

  日期：1996.7

  respectively. These analogs inhibited recombinant HIV reverse transcriptase with IC5() values of 62 μM and 1000 μM, respectively, whereas the IC5() value for michellamine B was 33 μM. Both michellamine B and the analogs inhibited the phosphorylation of histories by rat brain protein kinase C. The analogs were more active (IC50 values of 36 μM and 30 μM, respectively) than michellamine B (IC50 = 130 μM)

  二聚萘基四氢异喹啉生物碱米切胺B [4'，4“ -didesmethoxy-2'，2” -didesmethylmichellamine B和6,8-dihydroxy-5-（1'，1“ -dihydroxy-2'，2”的两个简化类似物-Suzuki钯催化的4-（2-苄基-6,8-二苄氧基-）的联芳基偶联反应合成了[ -binaphthalen-4'-yl）-1 R，3 R-二甲基-1,2,3,4-四氢异喹啉] 1 R，3 R-二甲基-1,2,3,4-四氢异喹啉-5-基）-1-苄氧基-2-溴萘分别转化为其相应的阻转异构体2-萘硼酸和1-苄氧基-2-萘硼酸。这些类似物抑制重组HIV逆转录酶与IC 5（）的62μ值中号和1000μ中号分别，而IC 5（）为michellamine B值为33μ中号。既michellamine B和类似物抑制历史的磷酸化的大鼠脑蛋白激酶C的类似物是多种活性（IC
• Stereospecific Syntheses of Michellamines A and C
  作者：Peter Hobbs、Velaparthi Upender、Marcia Dawson

  DOI：10.1055/s-1997-957

  日期：1997.8

  The total syntheses of two of the three dimeric naphthylisoquinoline michellamines - A and C - were achieved by Pd-catalyzed cross-coupling of the appropriate 6'-bromo- or 6'-boronic acid-substituted tetrabenzylated korupsensamine A and B derivatives under nonaqueous conditions, followed by deprotection of the octabenzylated products.

  在非水条件下，通过钯催化适当的 6'- 溴或 6'- 硼酸取代的四苄基柯鲁普森胺 A 和 B 衍生物的交叉偶联，然后对八苄基产物进行脱保护，实现了三种二聚萘基异喹啉小壳胺中的两种--A 和 C 的全合成。
• 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。
• A Convergent Total Synthesis of the Michellamines
  作者：Gerhard Bringmann、Roland Götz、Paul A. Keller、Rainer Walter、Michael R. Boyd、Fengrui Lang、Alberto Garcia、John J. Walsh、Imanol Tellitu、K. Vijaya Bhaskar、T. Ross Kelly

  DOI：10.1021/jo971495m

  日期：1998.2.1

  A convergent total synthesis of the anti-HIV michellamines (1) is described. The tetraaryl skeleton of the michellamines mas constructed by formation first of the inner (nonstereogenic) biaryl axis and subsequently of the two other (stereogenic) axes in a highly convergent manner. The key transformation features a double Suzuki-type cross-coupling reaction between binaphthalene ditriflate 26 and isoquinolineboronic acid 35. Ditriflate 26 is synthesized in six steps starting from diene 6 and 2,6-dibromobenzoquinone (9) in 21% overall yield. For large scale production of 26, a substantially shortened version of an existing procedure for the preparation of bisnaphthoquinone 13 was also developed, which allows far the preparation of 13 from benzoquinone and diene 6 in five steps and 67% overall yield. Binaphthoquinone 13 was subsequently converted into ditriflate 26 in three steps and 67% overall yield, By the described synthetic strategy, michellamines A (1a) and B (1b) are produced (1a:1b = 1:2.5) in 24.6% overall yield from diene 6. Curiously, none of the nonnaturally occurring atropoisomer 1c is formed.