[(1S),1R*,3S*,1'R*,3'S*]-5,5'-[1,1'-dihydroxy-8,8'-dimethoxy-6,6'-dimethyl(2,2'-binaphthalene)-4,4'-diyl]-bis-1,2,3,4-tetrahydro-1,2,3-trimethyl-6,8-isoquinolinediol

• 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: [(1S),1R*,3S*,1'R*,3'S*]-5,5'-[1,1'-dihydroxy-8,8'-dimethoxy-6,6'-dimethyl(2,2'-binaphthalene)-4,4'-diyl]-bis-1,2,3,4-tetrahydro-1,2,3-trimethyl-6,8-isoquinolinediol
• 英文别名: (1S,3R)-5-[3-[4-[(1S,3R)-6,8-dihydroxy-1,2,3-trimethyl-3,4-dihydro-1H-isoquinolin-5-yl]-1-hydroxy-8-methoxy-6-methyl-2-naphthyl]-4-hydroxy-5-methoxy-7-methyl-1-naphthyl]-1,2,3-trimethyl-3,4-dihydro-1H-isoquinoline-6,8-diol；(1S,3R)-5-[3-[4-[(1S,3R)-6,8-dihydroxy-1,2,3-trimethyl-3,4-dihydro-1H-isoquinolin-5-yl]-1-hydroxy-8-methoxy-6-methylnaphthalen-2-yl]-4-hydroxy-5-methoxy-7-methylnaphthalen-1-yl]-1,2,3-trimethyl-3,4-dihydro-1H-isoquinoline-6,8-diol
• 化学式: C₄₈H₅₂N₂O₈
• 分子量: 784.949
• InChiKey: JCDWHORNMUJTOW-XPGKHFPBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.2
• 重原子数：
  58
• 可旋转键数：
  5
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  146
• 氢给体数：
  6
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  (1S,3R)-(-)-6,8-dimethoxy-1,3-dimethyl-1,2,3,4-tetrahydroiso-quinoline 在 palladium on activated charcoal 、 四(三苯基膦)钯 盐酸 、 sodium tetrahydroborate 、 lithium aluminium tetrahydride 、 四丁基氟化铵 、 氢气 、 碘 、 三溴化硼 、 碳酸氢钠 、 potassium carbonate 、 silver sulfate 、 三乙胺 、 silver(l) oxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 乙醇 、 二氯甲烷 、 水 、 甲苯 、 丁酮 为溶剂， -78.0~110.0 ℃ 、101.33 kPa 条件下， 反应 126.0h， 生成 [(1S),1R*,3S*,1'R*,3'S*]-5,5'-[1,1'-dihydroxy-8,8'-dimethoxy-6,6'-dimethyl(2,2'-binaphthalene)-4,4'-diyl]-bis-1,2,3,4-tetrahydro-1,2,3-trimethyl-6,8-isoquinolinediol
  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

文献信息

• 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.