(S)-2-Hydrazino-3-phenyl-propionic acid methyl ester | 205748-85-2

• 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)-2-Hydrazino-3-phenyl-propionic acid methyl ester
• 英文别名: methyl (2S)-2-hydrazinyl-3-phenylpropanoate
• CAS: 205748-85-2
• 化学式: C₁₀H₁₄N₂O₂
• 分子量: 194.233
• InChiKey: VGRUCXOHFIEYHQ-VIFPVBQESA-N

物化性质

• 沸点：
  355.2±35.0 °C(Predicted)
• 密度：
  1.131±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  64.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-2-Hydrazino-3-phenyl-propionic acid methyl ester 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 (S)-2-hydrazinyl-3-phenylpropanoic acid
  参考文献：
  名称：

  Ribosome-Mediated Incorporation of Hydrazinophenylalanine into Modified Peptide and Protein Analogues

  摘要：

  (S)-alpha-Hydrazinophenylalanyl-tRNA(Phe), an amino acyl-tRNA derivative containing the unnatural amino acid (S)-alpha-hydrazinophenylalanine, was prepared in an effort to examine the stereochemical requirements of the A-site of the ribosome during in vitro protein synthesis. The (S)-alpha-hydrazinophenylalanine moiety was of interest because it contains two nucleophilic centers, the secondary nitrogen attached to Ca, which is normally acylated during the course of peptide bond formation, and the sterically less hindered primary nitrogen. To determine the position of acylation, (S)-alpha-hydrazinophenylalanyl-tRNA(Phe) was tested in an Escherichia coli in vitro protein biosynthesizing system lacking elongation factor G, such that only dipeptide products were formed. The dipeptide product mixture was analyzed by HPLC in direct comparison with authentic synthetic standards. The dipeptide assay utilizing (S)-alpha-hydrazinophenylalanyl-tRNA(Phe) as the A-site tRNA established that the analogue functioned well as an acceptor tRNA; HPLC analysis of the products showed that both dipeptides were formed in approximately equal amounts. When attached to a suppressor tRNA transcript, (S)-alpha-hydrazinophenylalanine was also incorporated into position 27 of dihydrofolate reductase in an E. coli protein synthesizing system by readthrough of a nonsense codon. This finding expands the currently accepted model of peptide bond formation at the ribosome and adds to the repertoire of peptide-like products shown to form at the peptidyltransferase center of the ribosome.

  DOI：

  10.1021/ja974066e
• 作为产物：
  描述：

  D-苯丙氨酸 在 2,6-二甲基吡啶 、 盐酸 、 硫酸 、 三氟乙酸 、 sodium nitrite 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 为溶剂， 反应 28.5h， 生成 (S)-2-Hydrazino-3-phenyl-propionic acid methyl ester
  参考文献：
  名称：

  Ribosome-Mediated Incorporation of Hydrazinophenylalanine into Modified Peptide and Protein Analogues

  摘要：

  (S)-alpha-Hydrazinophenylalanyl-tRNA(Phe), an amino acyl-tRNA derivative containing the unnatural amino acid (S)-alpha-hydrazinophenylalanine, was prepared in an effort to examine the stereochemical requirements of the A-site of the ribosome during in vitro protein synthesis. The (S)-alpha-hydrazinophenylalanine moiety was of interest because it contains two nucleophilic centers, the secondary nitrogen attached to Ca, which is normally acylated during the course of peptide bond formation, and the sterically less hindered primary nitrogen. To determine the position of acylation, (S)-alpha-hydrazinophenylalanyl-tRNA(Phe) was tested in an Escherichia coli in vitro protein biosynthesizing system lacking elongation factor G, such that only dipeptide products were formed. The dipeptide product mixture was analyzed by HPLC in direct comparison with authentic synthetic standards. The dipeptide assay utilizing (S)-alpha-hydrazinophenylalanyl-tRNA(Phe) as the A-site tRNA established that the analogue functioned well as an acceptor tRNA; HPLC analysis of the products showed that both dipeptides were formed in approximately equal amounts. When attached to a suppressor tRNA transcript, (S)-alpha-hydrazinophenylalanine was also incorporated into position 27 of dihydrofolate reductase in an E. coli protein synthesizing system by readthrough of a nonsense codon. This finding expands the currently accepted model of peptide bond formation at the ribosome and adds to the repertoire of peptide-like products shown to form at the peptidyltransferase center of the ribosome.

  DOI：

  10.1021/ja974066e

文献信息

• Stereoselective amination of chiral enolates. A new approach to the asymmetric synthesis of .alpha.-hydrazino and .alpha.-amino acid derivatives
  作者：David A. Evans、Thomas C. Britton、Roberta L. Dorow、Joseph F. Dellaria

  DOI：10.1021/ja00280a050

  日期：1986.10

  L'«amination» electrophile d'enolates chiraux derives d'acyl-3 oxazolidones par l'azoformiate de di-t-butyle permet la synthese d'α-hydrazino- et α-aminoacides

  L'«胺化» 亲电子 d'enolates chiraux 衍生 d'acyl-3 oxazolidones par l'azoformate de di-t-butyle permet la synthese d'α-hydrazino- et α-aminoacides
• [EN] DESACETOXYTUBULYSIN H AND ANALOGS THEREOF<br/>[FR] DÉSACÉTOXYTUBULYSINE H ET SES ANALOGUES
  申请人：UNIV RICE WILLIAM M

  公开号：WO2016138288A1

  公开（公告）日：2016-09-01

  In one aspect, the present disclosure provides tubulysin analogs of the formula (I) wherein R1, R2, R3, R4, X1, X2, X3, and A1 are as defined herein. In another aspect, the present disclosure also provides methods of preparing the compounds disclosed herein. In another aspect, the present disclosure also provides pharmaceutical compositions and methods of use of the compounds disclosed herein.

  在一个方面，本公开提供了公式（I）的tubulysin类似物，其中R1、R2、R3、R4、X1、X2、X3和A1如本文所定义。在另一个方面，本公开还提供了制备本公开化合物的方法。在另一个方面，本公开还提供了药物组合物和使用本公开化合物的方法。
• Total Synthesis and Biological Evaluation of Natural and Designed Tubulysins
  作者：K. C. Nicolaou、Jun Yin、Debashis Mandal、Rohan D. Erande、Philipp Klahn、Michael Jin、Monette Aujay、Joseph Sandoval、Julia Gavrilyuk、Dionisios Vourloumis

  DOI：10.1021/jacs.5b12557

  日期：2016.2.10

  A streamlined total synthesis of N(14)-desacetoxytubulysin H (Tb1) based on a C-H activation strategy and a short total synthesis of pretubulysin D (PTb-D43) are described. Applications of the developed synthetic strategies and technologies to the synthesis of a series of tubulysin analogues (Tb2-Tb41 and PTb-D42) are also reported. Biological evaluation of the synthesized compounds against an array

  描述了基于 CH 激活策略的 N(14)-去乙酰氧基微管溶素 H (Tb1) 的简化全合成和 pretubulysin D (PTb-D43) 的短全合成。还报告了所开发的合成策略和技术在合成一系列微管溶素类似物（Tb2-Tb41 和 PTb-D42）中的应用。针对一系列癌细胞的合成化合物的生物学评估揭示了许多新的类似物（例如，Tb14），其中一些对某些细胞系具有特殊的效力[例如，Tb32 对 MES SA（子宫肉瘤）细胞系的 IC50 = 12 pM和 2 pM 针对 HEK 293T（人胚胎肾）细胞系]，以及一组有价值的构效关系。
• RADIOLABELED PROSTATE SPECIFIC MEMBRANE ANTIGEN INHIBITORS
  申请人：Molecular Insight Pharmaceuticals

  公开号：US20150078998A1

  公开（公告）日：2015-03-19

  Compounds according to Formula I and Formula II are potent inhibitors of PSMA activity: Pharmaceutical compositions may include a complex of a radionuclide and a compound of Formula I or Formula II.

  公式 I 和公式 II 的化合物是 PSMA 活性的有效抑制剂：药物组合物可以包括放射性核素和公式 I 或公式 II 的化合物的复合物。
• US9388144B2
  申请人：——

  公开号：US9388144B2

  公开（公告）日：2016-07-12