(2E,4Z,6S,7S,8E,10S,11R,12S,14R)-11-(benzyloxy)-15-(3-bromo-2,5-diisopropoxy-6-methoxyphenyl)-6,12-dimethoxy-7-(methoxymethoxy)-2,8,10,14-tetramethylpentadeca-2,4,8-trienelactame | 1033591-59-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: (2E,4Z,6S,7S,8E,10S,11R,12S,14R)-11-(benzyloxy)-15-(3-bromo-2,5-diisopropoxy-6-methoxyphenyl)-6,12-dimethoxy-7-(methoxymethoxy)-2,8,10,14-tetramethylpentadeca-2,4,8-trienelactame
• 英文别名: (4E,6Z,8S,9S,10E,12S,13R,14S,16R)-8,14,19-trimethoxy-9-(methoxymethoxy)-4,10,12,16-tetramethyl-13-phenylmethoxy-20,22-di(propan-2-yloxy)-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18(22),19-hexaen-3-one
• CAS: 1033591-59-1
• 化学式: C₄₃H₆₃NO₉
• 分子量: 737.975
• InChiKey: LMPRFELMBMPQIY-AACQPJEMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  53
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (2E,4Z,6S,7S,8E,10S,11R,12S,14R)-11-(benzyloxy)-15-(3-bromo-2,5-diisopropoxy-6-methoxyphenyl)-6,12-dimethoxy-7-(methoxymethoxy)-2,8,10,14-tetramethylpentadeca-2,4,8-trienelactame 在 甲醇 、 乙酰氯 作用下， 以 乙醚 为溶剂， 反应 12.0h， 以91%的产率得到(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-13-(benzyloxy)-9-hydroxy-12,15-diisopropoxy-14,8,14-trimethoxy-4,10,12,16-tetramethyl-2-aza-1(1,3)-benzenacycloheptadecaphane-4,6,10-trien-3-one
  参考文献：
  名称：

  Total Synthesis of the Hsp90 Inhibitor Geldanamycin

  摘要：

  An enantioselective synthesis of the Hsp90 inhibitor geldanamycin was achieved in 20 linear steps and 2.0% overall yield from 2-methoxyhydroquinone. The synthesis is highlighted by a regio- and stereoselective hydroboration reaction; a Sc(OTf)(3)/Et(3)SiH-mediated pyran ring-opening reaction; an enantioselective crotylation to simultaneously install the C8-C9 (E)-trisubstituted olefin, the C10 and C11 stereocenters; a chelation-controlled asymmetric metallated acetylide addition; and an intramolecular copper(I)-mediated aryl amidation reaction to close the 19-membered macrolactam.

  DOI：

  10.1021/ol800749w
• 作为产物：
  描述：

  (2E,4Z,6S,7S,8E,10S,11R,12S,14R)-11-(benzyloxy)-15-(3-bromo-2,5-diisopropoxy-6-methoxyphenyl)-6,12-dimethoxy-7-(methoxymethoxy)-2,8,10,14-tetramethylpentadeca-2,4,8-trienamide 在 copper(l) iodide 、 potassium carbonate 、 N,N'-二甲基乙二胺 作用下， 以 甲苯 为溶剂， 反应 38.0h， 以81%的产率得到(2E,4Z,6S,7S,8E,10S,11R,12S,14R)-11-(benzyloxy)-15-(3-bromo-2,5-diisopropoxy-6-methoxyphenyl)-6,12-dimethoxy-7-(methoxymethoxy)-2,8,10,14-tetramethylpentadeca-2,4,8-trienelactame
  参考文献：
  名称：

  Total Synthesis of the Hsp90 Inhibitor Geldanamycin

  摘要：

  An enantioselective synthesis of the Hsp90 inhibitor geldanamycin was achieved in 20 linear steps and 2.0% overall yield from 2-methoxyhydroquinone. The synthesis is highlighted by a regio- and stereoselective hydroboration reaction; a Sc(OTf)(3)/Et(3)SiH-mediated pyran ring-opening reaction; an enantioselective crotylation to simultaneously install the C8-C9 (E)-trisubstituted olefin, the C10 and C11 stereocenters; a chelation-controlled asymmetric metallated acetylide addition; and an intramolecular copper(I)-mediated aryl amidation reaction to close the 19-membered macrolactam.

  DOI：

  10.1021/ol800749w

文献信息

• Total Synthesis of the Hsp90 Inhibitor Geldanamycin
  作者：Hua-Li Qin、James S. Panek

  DOI：10.1021/ol800749w

  日期：2008.6.1

  An enantioselective synthesis of the Hsp90 inhibitor geldanamycin was achieved in 20 linear steps and 2.0% overall yield from 2-methoxyhydroquinone. The synthesis is highlighted by a regio- and stereoselective hydroboration reaction; a Sc(OTf)(3)/Et(3)SiH-mediated pyran ring-opening reaction; an enantioselective crotylation to simultaneously install the C8-C9 (E)-trisubstituted olefin, the C10 and C11 stereocenters; a chelation-controlled asymmetric metallated acetylide addition; and an intramolecular copper(I)-mediated aryl amidation reaction to close the 19-membered macrolactam.