(2S,3aS,6R,7aS)-6-hydroxy-2,3,3a,4,5,6,7,7a-octahydroindole-1,2-dicarboxylic acid 1-benzyl ester 2-methyl ester | 320748-69-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S,3aS,6R,7aS)-6-hydroxy-2,3,3a,4,5,6,7,7a-octahydroindole-1,2-dicarboxylic acid 1-benzyl ester 2-methyl ester
• 英文别名: 1-benzyl 2-methyl (2S,3aS,6R,7aS)-6-hydroxyoctahydro-1H-indole-1,2-dicarboxylate
• CAS: 320748-69-4
• 化学式: C₁₈H₂₃NO₅
• 分子量: 333.384
• InChiKey: PKULBEVPMGUYEL-FZKCQIBNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  24.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  76.07
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (2S,3aS,6R,7aS)-6-hydroxy-2,3,3a,4,5,6,7,7a-octahydroindole-1,2-dicarboxylic acid 1-benzyl ester 2-methyl ester 在 palladium on activated charcoal 、 四(三苯基膦)钯 吡啶 、 咪唑 、 lithium hydroxide 、 iPr₂NEt₃ 、 五氟苯基二苯基磷酸酯 、 氢氟酸 、 氢气 、 三正丁基氢锡 、 溶剂黄146 、 N,N-二异丙基乙胺 、 3-(二乙氧基邻酰氧基)-1,2,3-苯并三嗪-4-酮 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 35.0 ℃ 、101.33 kPa 条件下， 反应 82.5h， 生成
  参考文献：
  名称：

  Total Synthesis and Stereochemical Revision of (+)-Aeruginosin 298-A

  摘要：

  [GRAPHICS]Novel routes toward both enantiomers of the bicyclic proline surrogate 2-carboxy-6-hydroxyoctahydroindole, i.e., Choi, were developed on the basis of the oxidative cyclization of L-tyrosine. Synthesis of the proposed sequence of (+)-aeruginosin 298-A did not provide the natural product. Incorporation of a D-leucine residue, in contrast, led to the total synthesis of this thrombin inhibitor.

  DOI：

  10.1021/ol006759x
• 作为产物：
  描述：

  (2S,3aS,7aS)-3a-(benzoyloxy)-6-oxo-2,3,3a,6,7,7a-hexahydroindole-1,2-dicarboxylic acid 1-benzyl ester 2-methyl ester 在 platinum(IV) oxide 氢气 、 L-Selectride 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醇 、 溶剂黄146 为溶剂， -78.0~65.0 ℃ 、101.33 kPa 条件下， 反应 13.0h， 生成 (2S,3aS,6R,7aS)-6-hydroxy-2,3,3a,4,5,6,7,7a-octahydroindole-1,2-dicarboxylic acid 1-benzyl ester 2-methyl ester
  参考文献：
  名称：

  Total Synthesis and Stereochemical Revision of (+)-Aeruginosin 298-A

  摘要：

  [GRAPHICS]Novel routes toward both enantiomers of the bicyclic proline surrogate 2-carboxy-6-hydroxyoctahydroindole, i.e., Choi, were developed on the basis of the oxidative cyclization of L-tyrosine. Synthesis of the proposed sequence of (+)-aeruginosin 298-A did not provide the natural product. Incorporation of a D-leucine residue, in contrast, led to the total synthesis of this thrombin inhibitor.

  DOI：

  10.1021/ol006759x

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。
• Investigating the Toxicity of the Aeruginosin Chlorosulfopeptides by Chemical Synthesis
  作者：Manuel Scherer、Dominik Bezold、Karl Gademann

  DOI：10.1002/anie.201602755

  日期：2016.8

  prevalent all over the world, and identification and mechanism‐of‐action studies of the responsible toxins serve to protect ecosystems, livestock, and humans alike. In this study, the chlorosulfopeptide aeruginosin 828A, which rivals the well‐known toxin microcystin LR in terms of crustacean toxicity, has been synthesized for the first time. Furthermore, three congeners with different permutations of the chloride

  有害的藻华在世界范围内日趋普遍，负责任毒素的鉴定和作用机理研究有助于保护生态系统，牲畜和人类。在这项研究中，首次合成了氯磺肽铜绿素酶828A，与甲壳素的毒性相媲美，该毒素与著名的微囊藻毒素LR相媲美。此外，制备了具有不同排列的氯和硫酸根基团的三个同类物，从而能够进行毒性研究，而没有被其他天然毒素污染的风险。用敏感的甲壳类沙棘头鼠的毒性试验表明，引入硫酸根基团会导致明显的毒性，而NMR光谱学证据表明，氯化物取代基可调节构象，
• Structure-based organic synthesis of unnatural aeruginosin hybrids as potent inhibitors of thrombin
  作者：Stephen Hanessian、Karolina Ersmark、Xiaotian Wang、Juan R. Del Valle、Niklas Blomberg、Yafeng Xue、Ola Fjellström

  DOI：10.1016/j.bmcl.2007.03.075

  日期：2007.6

  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.