(3SR,4SR)-1,4-dibenzyl-pyrrolidine-3-carboxylic acid ethyl ester

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (3SR,4SR)-1,4-dibenzyl-pyrrolidine-3-carboxylic acid ethyl ester
• 英文别名: ethyl trans-1,4-dibenzylpyrrolidine-3-carboxylate；ethyl (3S,4S)-1,4-dibenzylpyrrolidine-3-carboxylate
• 化学式: C₂₁H₂₅NO₂
• 分子量: 323.435
• InChiKey: WVBIIBRGJYFEBD-WOJBJXKFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3SR,4SR)-1,4-dibenzyl-pyrrolidine-3-carboxylic acid ethyl ester 在 lithium aluminium tetrahydride 、 palladium hydroxide, 20 wt% on carbon 、 氨 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 乙醇 为溶剂， 20.0 ℃ 、300.01 kPa 条件下， 反应 19.25h， 生成 (3R,4R,)-4-benzyl-1-t-butoxycarbonyl-3-hydroxymethylpyrrolidine
  参考文献：
  名称：

  Diastereodivergent Access to Syn and Anti 3,4-Substituted β-Fluoropyrrolidines: Enhancing or Reversing Substrate Preference

  摘要：

  A practical diastereodivergent access to beta-fluoropyrrolidines with two adjacent stereocenters has been demonstrated, by either enhancing or completely reversing the substrate control, in the diastereoselective fluorination of a series of diverse pyrrolidinyl carbaldehydes using organocatalysis. Furthermore, enamine catalysis has been successfully utilized for kinetic resolution, obtaining a fluorinated beta-prolinol analogue with two adjacent tetrasubstituted chiral centers in 95% ee from a racemic substrate.

  DOI：

  10.1021/acs.orglett.6b00293
• 作为产物：
  描述：

  苯乙醛 在 sodium hydride 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲苯 、 mineral oil 为溶剂， 反应 1.75h， 生成 (3SR,4SR)-1,4-dibenzyl-pyrrolidine-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  The Discovery of Novel Potenttrans-3,4-Disubstituted Pyrrolidine Inhibitors of the Human Aspartic Protease Renin from in Silico Three-Dimensional (3D) Pharmacophore Searches

  摘要：

  The small-molecule trans-3,4-disubstituted pyrrolidine 6 was identified from in silico three-dimensional (3D) pharmacophore searches based on known X-ray structures of renin-inhibitor complexes and demonstrated to be a weakly active inhibitor of the human enzyme. The unexpected binding mode of the more potent enantiomer (3S,4S)-6a in an extended conformation spanning the nonprime and S1' pockets of the recombinant human (rh)-renin active site was elucidated by X-ray crystallography. Initial structure-activity relationship work focused on modifications of the hydrophobic diphenylamine portion positioned in S1 and extending toward the S2 pocket. Replacement with an optimized P3-P1 pharmacophore interacting to the nonsubstrate S3(sp) cavity eventually resulted in significantly improved in vitro potency and selectivity. The prototype analogue (3S,4S)-12a of this new class of direct renin inhibitors exerted blood pressure lowering effects in a hypertensive double-transgenic rat model after oral administration.

  DOI：

  10.1021/jm3017078