(S)-1-((S)-2-tert-Butoxycarbonylamino-3-trimethylsilanyl-propionyl)-pyrrolidine-2-carboxylic acid | 142148-78-5

• 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: (S)-1-((S)-2-tert-Butoxycarbonylamino-3-trimethylsilanyl-propionyl)-pyrrolidine-2-carboxylic acid
• CAS: 142148-78-5
• 化学式: C₁₆H₃₀N₂O₅Si
• 分子量: 358.51
• InChiKey: LVFVVTHBDIHYIJ-NEPJUHHUSA-N

物化性质

• 沸点：
  515.8±50.0 °C(Predicted)
• 密度：
  1.119±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.29
• 重原子数：
  24.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  95.94
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (S)-1-((S)-2-tert-Butoxycarbonylamino-3-trimethylsilanyl-propionyl)-pyrrolidine-2-carboxylic acid 在 palladium on activated charcoal sodium azide 、 氢气 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 、 乙酸乙酯 为溶剂， -20.0~20.0 ℃ 、496.42 kPa 条件下， 反应 70.5h， 生成 tert-butyl N-[(2S)-1-[(2S)-2-[[(1R)-5-formamido-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]pentyl]carbamoyl]pyrrolidin-1-yl]-1-oxo-3-trimethylsilylpropan-2-yl]carbamate
  参考文献：
  名称：

  Selective boron-Containing thrombin inhibitors—X-ray analysis reveals surprising binding mode

  摘要：

  Based on the structural comparison of the S1 pocket in different trypsin-like serine proteases, a series of Boc-D-trimethylsilylalanine-proline-boro-X pinanediol derivatives, with boro-X being different amino boronic acids, have been synthesized as inhibitors of thrombin. Among the novel compounds, a number of derivatives were synthesized which appeared to have sidechain variants too big to fit into the S1 pocket. Nevertheless, these compounds inhibited thrombin in the nM range. The X-ray structure of one of these inhibitors bound to the active side of thrombin reveals that a new binding mode is responsible for these surprising results. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00147-4
• 作为产物：
  描述：

  (S)-N-(t-butoxycarbonyl)-β-(trimethylsilyl)alanine 在 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 为溶剂， 反应 36.0h， 生成 (S)-1-((S)-2-tert-Butoxycarbonylamino-3-trimethylsilanyl-propionyl)-pyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  Selective boron-Containing thrombin inhibitors—X-ray analysis reveals surprising binding mode

  摘要：

  Based on the structural comparison of the S1 pocket in different trypsin-like serine proteases, a series of Boc-D-trimethylsilylalanine-proline-boro-X pinanediol derivatives, with boro-X being different amino boronic acids, have been synthesized as inhibitors of thrombin. Among the novel compounds, a number of derivatives were synthesized which appeared to have sidechain variants too big to fit into the S1 pocket. Nevertheless, these compounds inhibited thrombin in the nM range. The X-ray structure of one of these inhibitors bound to the active side of thrombin reveals that a new binding mode is responsible for these surprising results. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00147-4

文献信息

• Design, synthesis and biological evaluation of selective boron-containing thrombin inhibitors
  作者：Anette Wienand、Claus Ehrhardt、Rainer Metternich、Carlo Tapparelli

  DOI：10.1016/s0968-0896(99)00069-3

  日期：1999.7

  Based on the structural comparison of the S-l pocket in different trypsin-like serine proteases, a series of Boc-D-trimethylsilylalanine-proline-boro-X pinanediol derivatives, with boro-X being different amino boronic acids, have been synthesised as inhibitors of thrombin. The influence of hydrogen donor/acceptor properties of different residues in the P-1 side chain of these inhibitors on the selectivity profile has been investigated. This study confirmed the structure-based working hypothesis: The hydrophobic/hydrophilic character of amino acid residues 190 and 213 in the neighbourhood of Asp 189 in the S-1 pocket of thrombin (Ala/Val), trypsin (Ser/Val) and plasmin (Ser/Thr) define the specificity for the interaction with different P-1 residues of the inhibitors. Many of the synthesised compounds demonstrate potent antithrombin activity with Boc-D-trimethylsilylalanine-proline-boro-methoxypropylglycine pinanediol (9) being the most selective thrombin inhibitor of this series. (C) 1999 Elsevier Science Ltd. All rights reserved.