4-amino-N-benzyloxycarbonyl-L-cis-proline

• 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: 4-amino-N-benzyloxycarbonyl-L-cis-proline
• 英文别名: (2S,4S)-4-azaniumyl-1-phenylmethoxycarbonylpyrrolidine-2-carboxylate
• 化学式: C₁₃H₁₆N₂O₄
• 分子量: 264.281
• InChiKey: ZQGCSLSUFLMTOP-QWRGUYRKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  92.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-amino-N-benzyloxycarbonyl-L-cis-proline 在 palladium on activated charcoal 氢气 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 20.0 ℃ 、310.26 kPa 条件下， 生成 (2S,4S)-4-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-ium-2-carboxylate
  参考文献：
  名称：

  Synthesis of Alanine and Proline Amino Acids with Amino or Guanidinium Substitution on the Side Chain

  摘要：

  Competitive binding of peptides containing basic amino acids to disrupt or prevent the Tat-TAR interaction could result in diminished transcription as well as translation and hence constitutes an alternative way of controlling HN replication. Therefore, we synthesized guanidinium and amino containing amino acids, based on a proline or an alanine scaffold. The introduction of the guanidinium moiety was best accomplished using 1H-pyrazole-1-carboxamidine hydrochloride, with Pmc used for its protection. The absence of racemization, maintained throughout the whole synthesis, was confirmed by chiral purity determination. These building blocks were smoothly incorporated into oligopeptides, which proved their suitability for use in a combinatorial approach for selecting TAR binding ligands. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(00)00123-x

文献信息

• HCV NS5A replication complex inhibitors. Part 2: Investigation of stilbene prolinamides
  作者：Denis R. St. Laurent、Makonen Belema、Min Gao、Jason Goodrich、Ramesh Kakarla、Jay O. Knipe、Julie A. Lemm、Mengping Liu、Omar D. Lopez、Van N. Nguyen、Peter T. Nower、Donald O’Boyle、Yuping Qiu、Jeffrey L. Romine、Michael H. Serrano-Wu、Jin-Hua Sun、Lourdes Valera、Fukang Yang、Xuejie Yang、Nicholas A. Meanwell、Lawrence B. Snyder

  DOI：10.1016/j.bmcl.2012.08.049

  日期：2012.10

  In a previous disclosure,(1) we reported the dimerization of an iminothiazolidinone to form 1, a contributor to the observed inhibition of HCV genotype 1b replicon activity. The dimer was isolated via bioassay-guided fractionation experiments and shown to be a potent inhibitor of genotype 1b HCV replication for which resistance mapped to the NS5A protein. The elements responsible for governing HCV inhibitory activity were successfully captured in the structurally simplified stilbene prolinamide 2. We describe herein the early SAR and profiling associated with stilbene prolinamides that culminated in the identification of analogs with PK properties sufficient to warrant continued commitment to this chemotype. These studies represent the key initial steps toward the discovery of daclatasvir (BMS-790052), a compound that has demonstrated clinical proof-of-concept for inhibiting the NS5A replication complex in the treatment of HCV infection. (C) 2012 Elsevier Ltd. All rights reserved.
• Synthesis of Alanine and Proline Amino Acids with Amino or Guanidinium Substitution on the Side Chain
  作者：Zhenyu Zhang、Arthur Van Aerschot、Chris Hendrix、Roger Busson、Frank David、Pat Sandra、Piet Herdewijn

  DOI：10.1016/s0040-4020(00)00123-x

  日期：2000.4

  Competitive binding of peptides containing basic amino acids to disrupt or prevent the Tat-TAR interaction could result in diminished transcription as well as translation and hence constitutes an alternative way of controlling HN replication. Therefore, we synthesized guanidinium and amino containing amino acids, based on a proline or an alanine scaffold. The introduction of the guanidinium moiety was best accomplished using 1H-pyrazole-1-carboxamidine hydrochloride, with Pmc used for its protection. The absence of racemization, maintained throughout the whole synthesis, was confirmed by chiral purity determination. These building blocks were smoothly incorporated into oligopeptides, which proved their suitability for use in a combinatorial approach for selecting TAR binding ligands. (C) 2000 Elsevier Science Ltd. All rights reserved.