(R)-2-acryloylamino-3-(3-chloro-4-methoxyphenyl)propionic acid 2,2,2-trichloroethyl ester | 1248798-73-3

• 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: (R)-2-acryloylamino-3-(3-chloro-4-methoxyphenyl)propionic acid 2,2,2-trichloroethyl ester
• 英文别名: (R)-2,2,2-trichloroethyl 2-acrylamido-3-(3-chloro-4-methoxyphenyl)propanoate；2,2,2-trichloroethyl (2R)-3-(3-chloro-4-methoxyphenyl)-2-(prop-2-enoylamino)propanoate
• CAS: 1248798-73-3
• 化学式: C₁₅H₁₅Cl₄NO₄
• 分子量: 415.1
• InChiKey: FJWXCACYUHPYJH-LLVKDONJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S,3S)-2-[(4R,5R)-2,2-dimethyl-5-phenyl-1,3-dioxolan-4-yl]hex-5-en-3-ol 、 (R)-2-acryloylamino-3-(3-chloro-4-methoxyphenyl)propionic acid 2,2,2-trichloroethyl ester 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 作用下， 以 二氯甲烷 为溶剂， 以78%的产率得到(R)-3-(3-Chloro-4-methoxy-phenyl)-2-[(E)-(5S,6S)-6-((4R,5R)-2,2-dimethyl-5-phenyl-[1,3]dioxolan-4-yl)-5-hydroxy-hept-2-enoylamino]-propionic acid 2,2,2-trichloro-ethyl ester
  参考文献：
  名称：

  Approaches for the Synthesis of Functionalized Cryptophycins

  摘要：

  The first syntheses of bioactive cryptophycins functionalized at unit ID were accomplished ina one-pot Staudinger reduction/cyclization step An a/ado precursor for the lower part of the backbone was introduced to minimize protective group chemistry and enable a very convenient synthesis of cryptophycin-52 and unit D eryptophycin analogues containing an ester or a free carboxylic acid for bioconjugations Both new cryptophycin derivatives show high biological activity in cytotoxicity assays

  DOI：

  10.1021/jo101563s
• 作为产物：
  描述：

  (R)-2-tert-butoxycarbonylamino-3-(3-chloro-4-methoxyphenyl)propionic acid 2,2,2-trichloroethyl ester 在 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 1.0h， 生成 (R)-2-acryloylamino-3-(3-chloro-4-methoxyphenyl)propionic acid 2,2,2-trichloroethyl ester
  参考文献：
  名称：

  Conjugates of Modified Cryptophycins and RGD-Peptides Enter Target Cells by Endocytosis

  摘要：

  Tumor targeting anticancer drug conjugates that contain a tumor recognition motif (homing device) are of high current relevance. Cryptophycins, naturally occurring cytotoxic cyclo-depsipeptides, have been modified by total synthesis to provide analogues suitable for conjugation to peptide-based homing devices. An array of functionalized beta(2)-amino acids was synthesized and incorporated into cryptophycins. All analogues proved to be highly active in the cytotoxicity assay using the human cervix carcinoma cell line KB-3-1 and its multidrug-resistant subclone KB-V1. Conformational analysis of cryptophycin-52 and two synthetic analogues was performed by NMR and MD methods to obtain information on the influence of the unit C configuration on the overall conformation. An azide-functionalized cryptophycin was connected by CuAAC to an alkyne-containing fluorescently labeled cyclic RGD-peptide as the homing device for internalization studies. Confocal fluorescence microscopy proved integrin-mediated internalization by endocytosis and final lysosomal localization of the cryptophycin prodrug.

  DOI：

  10.1021/jm301346z

文献信息

• Total synthesis and biological evaluation of fluorinated cryptophycins
  作者：Christine Weiß、Tobias Bogner、Benedikt Sammet、Norbert Sewald

  DOI：10.3762/bjoc.8.231

  日期：——

  Cryptophycins are cytotoxic natural products that exhibit considerable activities even against multi-drug-resistant tumor cell lines. As fluorinated pharmaceuticals have become more and more important during the past decades, fluorine-functionalized cryptophycins were synthesized and evaluated in cell-based cytotoxicity assays. The unit A trifluoromethyl-modified cryptophycin proved to be highly active against KB-3-1 cells and exhibited an IC₅₀ value in the low picomolar range. However, the replacement of the 3-chloro-4-methoxyphenyl-substituent in unit B by a pentafluorophenyl moiety resulted in a significant loss of activity.

  Cryptophycins是细胞毒性天然产物，甚至对多药耐药的肿瘤细胞系表现出相当大的活性。随着氟化制药在过去几十年变得越来越重要，氟功能化的Cryptophycins被合成并在基于细胞的细胞毒性实验中进行了评估。三氟甲基修饰的Cryptophycin A单元被证明对KB-3-1细胞非常活跃，并在低皮克摩尔范围内显示出IC50值。然而，将单元B中的3-氯-4-甲氧基苯基取代为五氟苯基团导致活性显著降低。
• Approaches for the Synthesis of Functionalized Cryptophycins
  作者：Benedikt Sammet、Tobias Bogner、Markus Nahrwold、Christine Weiss、Norbert Sewald

  DOI：10.1021/jo101563s

  日期：2010.10.15

  The first syntheses of bioactive cryptophycins functionalized at unit ID were accomplished ina one-pot Staudinger reduction/cyclization step An a/ado precursor for the lower part of the backbone was introduced to minimize protective group chemistry and enable a very convenient synthesis of cryptophycin-52 and unit D eryptophycin analogues containing an ester or a free carboxylic acid for bioconjugations Both new cryptophycin derivatives show high biological activity in cytotoxicity assays
• Conjugates of Modified Cryptophycins and RGD-Peptides Enter Target Cells by Endocytosis
  作者：Markus Nahrwold、Christine Weiß、Tobias Bogner、Felix Mertink、Jens Conradi、Benedikt Sammet、Ralf Palmisano、Soledad Royo Gracia、Thomas Preuße、Norbert Sewald

  DOI：10.1021/jm301346z

  日期：2013.3.14

  Tumor targeting anticancer drug conjugates that contain a tumor recognition motif (homing device) are of high current relevance. Cryptophycins, naturally occurring cytotoxic cyclo-depsipeptides, have been modified by total synthesis to provide analogues suitable for conjugation to peptide-based homing devices. An array of functionalized beta(2)-amino acids was synthesized and incorporated into cryptophycins. All analogues proved to be highly active in the cytotoxicity assay using the human cervix carcinoma cell line KB-3-1 and its multidrug-resistant subclone KB-V1. Conformational analysis of cryptophycin-52 and two synthetic analogues was performed by NMR and MD methods to obtain information on the influence of the unit C configuration on the overall conformation. An azide-functionalized cryptophycin was connected by CuAAC to an alkyne-containing fluorescently labeled cyclic RGD-peptide as the homing device for internalization studies. Confocal fluorescence microscopy proved integrin-mediated internalization by endocytosis and final lysosomal localization of the cryptophycin prodrug.