Boc-Phe-NH(CH2)3OH | 120125-31-7

• 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: Boc-Phe-NH(CH2)3OH
• 英文别名: tert-butyl (S)-(1-((3-hydroxypropyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate；tert-butyl N-[1-benzyl-2-(3-hydroxypropylamino)-2-oxoethyl]carbamate；Tert-butyl N-[(1S)-1-[(3-hydroxypropyl)carbamoyl]-2-phenylethyl]carbamate；tert-butyl N-[(2S)-1-(3-hydroxypropylamino)-1-oxo-3-phenylpropan-2-yl]carbamate
• CAS: 120125-31-7
• 化学式: C₁₇H₂₆N₂O₄
• 分子量: 322.404
• InChiKey: WFGHGFOZUQBMGY-AWEZNQCLSA-N

物化性质

• 沸点：
  562.4±50.0 °C(Predicted)
• 密度：
  1.123±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  87.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Boc-Phe-NH(CH2)3OH 在 盐酸 、 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.5h， 生成 Phenylalanine hydroxypropylamide
  参考文献：
  名称：

  Pyridoxal 5′-Phosphate Binding in Lysine-Modified PAMAM Dendrimers: A Biomimetic Approach

  摘要：

  (G:3-7)-dendri-PAMAM-(APO-Phe-Lys)(x) (2, APO = aminopropanol, Phe = phenylalanine, Lys = lysine) were prepared and used in a binding study with pyridoxal 5'-phosphate. The results revealed a positive dendritic effect, and binding ability was found to vary with the environment. (G:3-7)-dendri-PAMAM-(APO-Phe-Lys),, (2) demonstrated better binding ability at higher pH, and protonation of lysine was considered to affect binding. The strongest binding affinity was K-b = 254.3 mM(-1) at pH 9, which was shown by (G:7)-dendri-PAMAM-(APO-Phe-LYS)(490) (2e).

  DOI：

  10.1021/ol901299e
• 作为产物：
  描述：

  BOC-L-苯丙氨酸 、 3-氨基-1-丙醇 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以81%的产率得到Boc-Phe-NH(CH2)3OH
  参考文献：
  名称：

  共轭弹头的工艺开发和 GMP 生产：Auristatin F-HPA-Ala/TFA (XMT-1864/TFA)

  摘要：

  为 XMT-1864/TFA ( 1-TFA)，一种 auristatin F 衍生物，在 Mersana 的肿瘤抗体-药物偶联物平台中用作新型、高效、细胞毒性弹头。该工艺实现了高非对映异构体纯度，并控制了所有中间体的杂质，所有中间体均可通过结晶或沉淀以高产率和纯度轻松分离。选择保护基团以确保中间体在各种溶液相肽偶联条件下的耐受性、可扩展性和稳定性。开发最终产品的结晶以去除特定的杂质并提供用于生物共轭加工的高纯度活性弹头分子。涉及六个非 GMP 步骤和五个 GMP 步骤的聚合合成已在多个 1-kg 规模的 cGMP 生产中进行，以生产1-TFA在 >98% 的化学纯度和 <1% 的总非对映异构体污染中，GMP 步骤的总收率约为 50%。

  DOI：

  10.1021/acs.oprd.1c00449

文献信息

• Studies on analgesic oligopeptides. V. Structure-activity relationship of tripeptide alkylamides, Tyr-D-Arg-Phe-X.
  作者：KENJI SUZUKI、HIROKI FUJITA、YUSUKE SASAKI、MIKI SHIRATORI、SHINOBU SAKURADA、KENSUKE KISARA

  DOI：10.1248/cpb.36.4834

  日期：——

  Twenty-one analogs based on the structure Tyr-D-Arg-Phe-X (X=OH, alkyl ester, alkylamide or amino acid having a different carbon chain) were synthesized by the solution method and their analgesic activities were tested after subcutaneous (s. c.) administration in mice. Most tripeptide alkylamides showed no analgesia at a dose of 10 mg/kg, s. c. However, some tripeptide alkylamides having the hydroxyl group on the alkyl moiety showed greater activity than morphine. Introduction of the carboxyl group on the alkyl moiety also led to tetrapeptide analogs with potent analgesia, e. g., the compound with X=β-alanine is 33 times more potent than morphine on a molar basis. These results suggest that proper carbon chain lengths and the presence of an oxygen atom at the fourth position are important for high analgesic activity in the series of D-Arg2-dermorphin analogs.

  通过溶液法合成了基于结构Tyr-D-Arg-Phe-X（X=OH，烷基酯，烷基酰胺或具有不同碳链的氨基酸）的21种类似物，并在小鼠皮下（s.c.）给药后测试了它们的镇痛活性。大多数三肽烷基酰胺在10 mg/kg，s.c.剂量下没有镇痛作用。然而，一些在烷基部分具有羟基的三肽烷基酰胺显示出比吗啡更大的活性。在烷基部分引入羧基也导致具有强效镇痛作用的四肽类似物，例如，X=β-丙氨酸的化合物在摩尔基础上比吗啡强33倍。这些结果表明，适当的碳链长度和在第四位存在氧原子对于D-Arg2-dermorphin类似物系列中的高镇痛活性是重要的。
• SUZUKI, KENJI;FUJITA, HIROKI;SASAKI, YUSUKE;SHIRATORI, MIKI;SAKURADA, SHI+, CHEM. AND PHARM. BULL., 36,(1988) N2, C. 4834-4840
  作者：SUZUKI, KENJI、FUJITA, HIROKI、SASAKI, YUSUKE、SHIRATORI, MIKI、SAKURADA, SHI+

  DOI：——

  日期：——
• Pyridoxal 5′-Phosphate Binding in Lysine-Modified PAMAM Dendrimers: A Biomimetic Approach
  作者：Kuang-Chan Hsien、Hui-Ting Chen、Yi-Chen Chen、Yeh-Long Chen、Chi-Yu Lu、Chai-Lin Kao

  DOI：10.1021/ol901299e

  日期：2009.8.20

  (G:3-7)-dendri-PAMAM-(APO-Phe-Lys)(x) (2, APO = aminopropanol, Phe = phenylalanine, Lys = lysine) were prepared and used in a binding study with pyridoxal 5'-phosphate. The results revealed a positive dendritic effect, and binding ability was found to vary with the environment. (G:3-7)-dendri-PAMAM-(APO-Phe-Lys),, (2) demonstrated better binding ability at higher pH, and protonation of lysine was considered to affect binding. The strongest binding affinity was K-b = 254.3 mM(-1) at pH 9, which was shown by (G:7)-dendri-PAMAM-(APO-Phe-LYS)(490) (2e).
• Process Development and GMP Production of a Conjugate Warhead: Auristatin F-HPA-Ala/TFA (XMT-1864/TFA)
  作者：Patrick R. Conlon、Venu Reddy Gurijala、Michael Kaufman、Dachang Li、Jiuyuan Li、Yuanyuan Li、Mao Yin、Bollu Satyanarayan Reddy、Thomas Wagler、Zedong Wang、Zhongmin Xu、Aleksandr V. Yurkovetskiy、Lei Zhu

  DOI：10.1021/acs.oprd.1c00449

  日期：2022.8.19

  large-scale manufacturing process is described for XMT-1864/TFA (1-TFA), an auristatin F derivative, used as a novel, highly potent, cytotoxic warhead in Mersana’s oncology antibody–drug conjugate platforms. The process achieves high diastereomeric purity and controls the impurities with all intermediates readily isolated by crystallization or precipitation in high yield and purity. Protecting groups were

  为 XMT-1864/TFA ( 1-TFA)，一种 auristatin F 衍生物，在 Mersana 的肿瘤抗体-药物偶联物平台中用作新型、高效、细胞毒性弹头。该工艺实现了高非对映异构体纯度，并控制了所有中间体的杂质，所有中间体均可通过结晶或沉淀以高产率和纯度轻松分离。选择保护基团以确保中间体在各种溶液相肽偶联条件下的耐受性、可扩展性和稳定性。开发最终产品的结晶以去除特定的杂质并提供用于生物共轭加工的高纯度活性弹头分子。涉及六个非 GMP 步骤和五个 GMP 步骤的聚合合成已在多个 1-kg 规模的 cGMP 生产中进行，以生产1-TFA在 >98% 的化学纯度和 <1% 的总非对映异构体污染中，GMP 步骤的总收率约为 50%。