(3R)-(+)-6,8-dimethoxy-1,3-dimethyl-3,4-dihydroisoquinoline | 178150-76-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氢异喹啉
• 英文名称: (3R)-(+)-6,8-dimethoxy-1,3-dimethyl-3,4-dihydroisoquinoline
• 英文别名: (R)-3,4-dihydro-6,8-dimethoxy-1,3-dimethylisoquinoline；(3R)-6,8-dimethoxy-1,3-dimethyl-3,4-dihydroisoquinoline
• CAS: 178150-76-0
• 化学式: C₁₃H₁₇NO₂
• 分子量: 219.283
• InChiKey: GZBGZFKNOCVESD-MRVPVSSYSA-N

物化性质

• 沸点：
  344.4±42.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  30.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3R)-(+)-6,8-dimethoxy-1,3-dimethyl-3,4-dihydroisoquinoline 在 lithium aluminium tetrahydride 、 三甲基铝 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 27.5h， 生成 (1R,3R)-2-benzyl-6,8-dimethoxy-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  两种抗HIV生物碱Michellamine B的合成及其生物学活性

  摘要：

  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

  DOI：

  10.1002/jhet.5570330460
• 作为产物：
  描述：

  (R,R)-N-<1-(3,5-dimethoxyphenyl)-2-propyl>-α-methylbenzenemethanamine 在 钯 甲酸铵 、 三乙胺 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 (3R)-(+)-6,8-dimethoxy-1,3-dimethyl-3,4-dihydroisoquinoline
  参考文献：
  名称：

  Total synthesis of Michellamines A-C: Important anti-HIV agents

  摘要：

  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.

  DOI：

  10.1016/s0040-4039(00)78487-5

文献信息

• Design of Phosphorus Ligands with Deep Chiral Pockets: Practical Synthesis of Chiral β-Arylamines by Asymmetric Hydrogenation
  作者：Guodu Liu、Xiangqian Liu、Zhihua Cai、Guangjun Jiao、Guangqing Xu、Wenjun Tang

  DOI：10.1002/anie.201300646

  日期：2013.4.8

  WingPhos, a C2‐symmetric bisphosphorus ligand with a deep and well‐defined chiral pocket was developed. It has shown high efficiency in the rhodium‐catalyzed asymmetric hydrogenation of (E)‐β‐aryl‐N‐acetyl enamides, cyclic β‐aryl enamides, and heterocyclic β‐aryl enamides. A series of chiral β‐arylisopropylamines, 2‐aminotetralines, and 3‐aminochromans can be synthesized with excellent ee values (nbd=3

  WingPhos是一种C 2对称的双磷配体，具有较深且定义明确的手性口袋。在（E）-β-芳基-N-乙酰基酰胺，环状β-芳基酰胺和杂环β-芳基酰胺的铑催化不对称氢化反应中显示出很高的效率。可以合成一系列具有良好ee值（nbd = 3,5-降冰片二烯； TON =周转数）的手性β-芳基异丙胺，2-氨基四氢呋喃和3-氨基苯并二氢吡喃。
• Sulfinimine-Mediated Asymmetric Synthesis of 1,3-Disubstituted Tetrahydroisoquinolines:  A Stereoselective Synthesis of <i>cis</i>- and <i>trans</i>-6,8-Dimethoxy-1,3-dimethyl- 1,2,3,4-tetrahydroisoquinoline
  作者：Franklin A. Davis、Pradyumna K. Mohanty、David M. Burns、Yemane W. Andemichael

  DOI：10.1021/ol006654u

  日期：2000.11.1

  lithiated o-tolunitriles to sulfinimines followed by treatment of the resulting sulfinamide with MeLi, hydrolysis, and reduction represents a concise new methodology for the asymmetric synthesis of 1,3-disubstituted tetrahydroisoquinolines.

  [反应：见正文]在亚磺胺中高度非对映选择性地将侧基锂化邻甲苯二酚加成，然后用MeLi处理所得的亚磺酰胺，进行水解和还原反应，代表了一种简洁的新方法，用于不对称合成1,3-二取代的四氢异喹啉。
• Asymmetric synthesis of alkaloids using polyfunctionalized chiral building blocks
  作者：Franklin A. Davis、Bin Chao、Yemane W. Andemichael、Pradyumna K. Mohanty、Tianan Fang、David M. Burns、Ashwin Rao、Joanna M. Szewczyk

  DOI：10.1002/hc.10090

  日期：——

  Enantiopure N-sulfinyl-δ-amino-β-ketoesters and isoquinolones, prepared from sulfinimines (N-sulfinyl imines) are a new class of polyfunctionalized chiral building blocks. These building blocks provide easy access to enantiomerically pure, functionalized piperidines and tetrahydroisoquinolines with a minimum of chemical manipulation and protecting-group chemistry. © 2002 Wiley Periodicals, Inc. Heteroatom

  由亚磺亚胺（N-亚磺酰基亚胺）制备的对映体纯 N-亚磺酰基-δ-氨基-β-酮酯和异喹诺酮类是一类新的多官能化手性结构单元。这些结构单元可轻松获得对映异构纯的官能化哌啶和四氢异喹啉，且化学操作和保护基团化学最少。© 2002 Wiley Periodicals, Inc. 杂原子化学 13:486–492, 2002; 在线发表于 Wiley Interscience (www.interscience.wiley.com)。DOI 10.1002/hc.10090
• Total synthesis of (ent)-korupensamine D
  作者：Thomas R. Hoye、Minzhang Chen

  DOI：10.1016/0040-4039(96)00524-2

  日期：1996.4

  enantiomer of the natural product, korupensamine D (16R), is described. The key steps include a highly efficient preparation of the enantiomerically pure primary amine 4 via the ring opening of aziridine 2 with an arylcuprate reagent and the development of a one-pot selective functionalization of a hindered secondary amine in the presence of phenolic hydroxyl groups (i.e., 8 to 9).

  描述了天然产物对映异构体D（16R）的对映异构体的第一次全合成。关键步骤包括通过氮丙啶2与芳基铜酸酯试剂的开环高效制备对映体纯的伯胺4以及在酚羟基存在的情况下开发受阻仲胺的一锅选择性功能化，8至9）。
• Total Synthesis of Michellamines A−C, Korupensamines A−D, and Ancistrobrevine B
  作者：Thomas R. Hoye、Minzhang Chen、Bac Hoang、Liang Mi、Owen P. Priest

  DOI：10.1021/jo9908187

  日期：1999.9.1

  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.