(2S,3aS,6R,7aS)-1-((benzyloxy)carbonyl)-6-((tert-butyldimethylsilyl)oxy)octahydro-1H-indole-2-carboxylic acid | 945405-59-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2S,3aS,6R,7aS)-1-((benzyloxy)carbonyl)-6-((tert-butyldimethylsilyl)oxy)octahydro-1H-indole-2-carboxylic acid
• CAS: 945405-59-4
• 化学式: C₂₃H₃₅NO₅Si
• 分子量: 433.62
• InChiKey: WNLHZFHNNCKWAL-YRPNKDGESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.04
• 重原子数：
  30.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  76.07
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (2S,3aS,6R,7aS)-1-((benzyloxy)carbonyl)-6-((tert-butyldimethylsilyl)oxy)octahydro-1H-indole-2-carboxylic acid 在 palladium dihydroxide 2,6-二甲基吡啶 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氢气 、 3-(二乙氧基邻酰氧基)-1,2,3-苯并三嗪-4-酮 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 生成
  参考文献：
  名称：

  Structure-based organic synthesis of unnatural aeruginosin hybrids as potent inhibitors of thrombin

  摘要：

  Based on X-ray crystallographic data of complexes of chlorodysinosin A with the enzyme thrombin, a series of analogs were synthesized varying the nature of the P-1, P-2, and P-3 pharmacophoric sites and the central octahydroindole carboxyamide core. In general, introduction of a hydrophobic substituent on the D-leucine amide residue dramatically improved the inhibition of the enzyme. This is rationalized based on a better fit of the P-3 subunit in the hydrophobic S-3 enzyme site. Single digit nanomolar inhibition expressed as IC50 was observed for several analogs. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.075
• 作为产物：
  描述：

  叔丁基二甲硅基三氟甲磺酸酯 在 lithium hydroxide 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (2S,3aS,6R,7aS)-1-((benzyloxy)carbonyl)-6-((tert-butyldimethylsilyl)oxy)octahydro-1H-indole-2-carboxylic acid
  参考文献：
  名称：

  Structure-based organic synthesis of unnatural aeruginosin hybrids as potent inhibitors of thrombin

  摘要：

  Based on X-ray crystallographic data of complexes of chlorodysinosin A with the enzyme thrombin, a series of analogs were synthesized varying the nature of the P-1, P-2, and P-3 pharmacophoric sites and the central octahydroindole carboxyamide core. In general, introduction of a hydrophobic substituent on the D-leucine amide residue dramatically improved the inhibition of the enzyme. This is rationalized based on a better fit of the P-3 subunit in the hydrophobic S-3 enzyme site. Single digit nanomolar inhibition expressed as IC50 was observed for several analogs. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.075

文献信息

• Total Synthesis and Structural Revision of the Presumed Aeruginosins 205A and B
  作者：Stephen Hanessian、Xiaotian Wang、Karolina Ersmark、Juan R. Del Valle、Ellen Klegraf

  DOI：10.1021/ol901702k

  日期：2009.9.17

  A stereoselective synthesis of enantiopure aeruginosin 205B aglycon confirms the presence of a (3R,2S)-3-chloroleucine amide residue and a (6R)-hydroxy (4aR,7aS)-octahydroindole-(2S)-2-carboxamide (Choi) subunit instead of a 6-chloro-substituted core (Ccoi). Enzyme inhibitory tests against thrombin revealed an IC50 of 0.31 μM. The total synthesis of the presumed aeruginosin 205B shows that the α-d-xylopyranosyl

  立体选择性合成对映体纯铜绿蛋白酶205B糖苷配基证实存在（3 R，2 S）-3-氯亮氨酸酰胺残基和（6 R）-羟基（4a R，7a S）-八氢吲哚-（2 S）-2 -羧酰胺（Choi）亚基，而不是6-氯取代的核心（Ccoi）。酶对凝血酶的抑制试验显示IC 50为0.31μM。推测的铜绿素酶205B的总合成表明，α- d-木吡喃糖基单元在C-4'处（而不是在C-3'处）具有硫酸根基团。NMR数据的比较导致了铜绿素205A的相同修订。