benzyloxycarbonyl-L-tyrosyl-D-alaninemethylester | 35790-08-0

• 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: benzyloxycarbonyl-L-tyrosyl-D-alaninemethylester
• 英文别名: methyl (2R)-2-[[(2S)-3-(4-hydroxyphenyl)-2-(phenylmethoxycarbonylamino)propanoyl]amino]propanoate
• CAS: 35790-08-0
• 化学式: C₂₁H₂₄N₂O₆
• 分子量: 400.431
• InChiKey: QTVLQZKFEDHRLP-KDOFPFPSSA-N

物化性质

• 沸点：
  650.1±55.0 °C(Predicted)
• 密度：
  1.253±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  benzyloxycarbonyl-L-tyrosyl-D-alaninemethylester 在 N-甲基吗啉 、 水 、 sodium hydroxide 、 氯甲酸异丁酯 作用下， 以 丙酮 为溶剂， 生成 CBz-Tyr-D-Ala-Phe(F)-Phe-NH2
  参考文献：
  名称：

  Frakefamide, an Analgesic Tetrapeptide:  Development of a Pilot-Plant-Scale Process

  摘要：

  A pilot-plant-process is described where frakefamide x HCl (L-tyrosyl-D-alanyl-p-fluoro-L-phenylalanyl-L-phenylalaninamide hydrochloride) was synthesised from its amino acid monomers in seven steps. The synthesis was performed in 70-L equipment, and the final product was obtained in 70% overall yield and in 99.5% purity. Only two intermediates were isolated, and the process required no chromatography. Peptide bond formation was promoted by isobutyl chloroformate-mediated mixed anhydride coupling reactions. The formed mixed anhydrides proved to be surprisingly stable, in most cases for several hours at -10 degreesC, and therefore suitable for large-scale peptide synthesis. Only traces, if any, of racemised coupling products were obtained. Benzyloxycarbonyl was used as amino protecting group throughout the synthesis, and its removal by hydrogenolysis proved to be fast and convenient on a large scale.

  DOI：

  10.1021/op020060k
• 作为产物：
  描述：

  N-苄氧羰基-L-酪氨酸 、 D-丙氨酸甲酯盐酸盐 在 N-甲基吗啉 、 氯甲酸异丁酯 作用下， 以 丙酮 为溶剂， 生成 benzyloxycarbonyl-L-tyrosyl-D-alaninemethylester
  参考文献：
  名称：

  Frakefamide, an Analgesic Tetrapeptide:  Development of a Pilot-Plant-Scale Process

  摘要：

  A pilot-plant-process is described where frakefamide x HCl (L-tyrosyl-D-alanyl-p-fluoro-L-phenylalanyl-L-phenylalaninamide hydrochloride) was synthesised from its amino acid monomers in seven steps. The synthesis was performed in 70-L equipment, and the final product was obtained in 70% overall yield and in 99.5% purity. Only two intermediates were isolated, and the process required no chromatography. Peptide bond formation was promoted by isobutyl chloroformate-mediated mixed anhydride coupling reactions. The formed mixed anhydrides proved to be surprisingly stable, in most cases for several hours at -10 degreesC, and therefore suitable for large-scale peptide synthesis. Only traces, if any, of racemised coupling products were obtained. Benzyloxycarbonyl was used as amino protecting group throughout the synthesis, and its removal by hydrogenolysis proved to be fast and convenient on a large scale.

  DOI：

  10.1021/op020060k

文献信息

• [EN] PROCESS FOR THE PREPARATION OF A TETRAPEPTIDE<br/>[FR] PROCEDE DE PREPARATION D'UN TETRAPEPTIDE
  申请人：ASTRAZENECA AB

  公开号：WO1999047548A1

  公开（公告）日：1999-09-23

  (EN) The present invention discloses a new and improved process for the preparation of the tetrapeptide H-Tyr-D-Ala-Phe(F)-Phe-NH2 which is a peptide of formula (I) or a pharmaceutically acceptable salt thereof, as well as new intermediates in the preparation thereof. The novel process is suitable for large scale production.(FR) La présente invention concerne un nouveau procédé amélioré de préparation du tétrapeptide H-Tyr-D-Ala-Phe(F)-Phe-NH2 qui est un peptide de la formule (I) ou d'un sel de ce peptide acceptable du point de vue pharmaceutique, ainsi que de nouveaux intermédiaires dans la préparation de ce peptide. Le nouveau procédé selon l'invention convient à une production à grande échelle.

  (中文翻译) 本发明揭示了一种新的和改进的制备H-Tyr-D-Ala-Phe(F)-Phe-NH2四肽或其药学上可接受的盐的过程，以及制备过程中的新中间体。这种新的过程适用于大规模生产。
• [EN] A PROCESS FOR THE PREPARATION OF H-TYR-D-ALA-PHE(F)-PHE-NH2<br/>[FR] PROCEDE DE PREPARATION DE H-TYR-D-ALA-PHE(F)-PHE-NH2
  申请人：ASTRAZENECA AB

  公开号：WO2001019849A1

  公开（公告）日：2001-03-22

  The present invention discloses a new and improved process for the preparation of the tetrapeptide H-Tyr-D-Ala-Phe(F)-Phe-NH2 that is a peptide of formula (I), or a pharmaceutically acceptable salt thereof, as well as new intermediates in the preparation thereof. The novel process is a fragment synthesis and suitable for large-scale production.

  本发明揭示了一种新的、改进的四肽H-Tyr-D-Ala-Phe(F)-Phe-NH2的制备方法，该四肽的化学式为(I)，或其药学上可接受的盐，以及其制备中的新中间体。这种新的方法是一种片段合成方法，适用于大规模生产。
• US4496540A
  申请人：——

  公开号：US4496540A

  公开（公告）日：1985-01-29