methyl (8aR,9S)-1,5-dibromo-4-hydroxy-3-methoxy-6-oxo-6,7,8,8a,9,10-hexahydro-9-phenanthrenecarboxylate | 193679-33-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: methyl (8aR,9S)-1,5-dibromo-4-hydroxy-3-methoxy-6-oxo-6,7,8,8a,9,10-hexahydro-9-phenanthrenecarboxylate
• 英文别名: methyl (8aR,9S)-1,5-dibromo-4-hydroxy-3-methoxy-6-oxo-8,8a,9,10-tetrahydro-7H-phenanthrene-9-carboxylate
• CAS: 193679-33-3
• 化学式: C₁₇H₁₆Br₂O₅
• 分子量: 460.119
• InChiKey: UEGUYYKULYOVDG-SFYZADRCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl (8aR,9S)-1,5-dibromo-4-hydroxy-3-methoxy-6-oxo-6,7,8,8a,9,10-hexahydro-9-phenanthrenecarboxylate 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 苯 为溶剂， 反应 4.0h， 以90%的产率得到methyl (7aR,8S)-1-bromo-3-methoxy-6-oxo-5,6,7,7a,8,9-hexahydrophenanthro[4,5-bcd]furan-8-carboxylate
  参考文献：
  名称：

  Asymmetric Total Synthesis of (+)-Codeine via Intramolecular Carbenoid Insertion

  摘要：

  A strategy was devised for the synthesis of codeine that employed intramolecular insertion of a carbenoid into a benzylic methine CH bond for creation of the C13 quaternary center and construction of the pentacyclic skeleton of the alkaloid. The synthesis began from isovanillin, and asymmetry was introduced through catalytic hydrogenation of its Stobbe condensation product 7 over a chiral catalyst (8). The product (S)-9 was advanced to tetralone 12, which underwent Robinson annulation to give the phenanthrenone 33. The latter was brominated and treated with base to afford the fused benzofuran 35. Reduction with hydride followed by catalytic hydrogenation produced the tetracycle 44, which was converted to diazoketone 48. The latter was reacted in the presence of catalytic Rh-2(OAc)(4) to furnish the pentacyclic product 49. Beckmann rearrangement of the derived oxime brosylate 59 gave lactam 57, and the synthesis of (+)-1 (the nonnatural enantiomer of codeine) was completed after oxidation to 63, introduction of Delta(7,8) unsaturation, and exhaustive reduction.

  DOI：

  10.1021/jo990905z
• 作为产物：
  描述：

  methyl (2S)-5-hydroxy-6-methoxy-4-oxo-1,2,3,4-tetrahydro-2-naphthalenecarboxylate 在 lithium hydroxide 、 sodium hydroxide 、 溴 、 potassium hydride 、 碳酸氢钠 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 氯仿 、 水 、 乙酸乙酯 为溶剂， 反应 42.0h， 生成 methyl (8aR,9S)-1,5-dibromo-4-hydroxy-3-methoxy-6-oxo-6,7,8,8a,9,10-hexahydro-9-phenanthrenecarboxylate
  参考文献：
  名称：

  Asymmetric Total Synthesis of (+)-Codeine via Intramolecular Carbenoid Insertion

  摘要：

  A strategy was devised for the synthesis of codeine that employed intramolecular insertion of a carbenoid into a benzylic methine CH bond for creation of the C13 quaternary center and construction of the pentacyclic skeleton of the alkaloid. The synthesis began from isovanillin, and asymmetry was introduced through catalytic hydrogenation of its Stobbe condensation product 7 over a chiral catalyst (8). The product (S)-9 was advanced to tetralone 12, which underwent Robinson annulation to give the phenanthrenone 33. The latter was brominated and treated with base to afford the fused benzofuran 35. Reduction with hydride followed by catalytic hydrogenation produced the tetracycle 44, which was converted to diazoketone 48. The latter was reacted in the presence of catalytic Rh-2(OAc)(4) to furnish the pentacyclic product 49. Beckmann rearrangement of the derived oxime brosylate 59 gave lactam 57, and the synthesis of (+)-1 (the nonnatural enantiomer of codeine) was completed after oxidation to 63, introduction of Delta(7,8) unsaturation, and exhaustive reduction.

  DOI：

  10.1021/jo990905z

文献信息

• Asymmetric Synthesis of (+)-Morphine. The Phenanthrene Route Revisited
  作者：James D. White、Peter Hrnciar、Frank Stappenbeck

  DOI：10.1021/jo9710994

  日期：1997.8.1