(R)-2-tert-butoxycarbonylamino-3-(3-chloro-4-methoxyphenyl)propionic acid 2,2,2-trichloroethyl ester

• 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-tert-butoxycarbonylamino-3-(3-chloro-4-methoxyphenyl)propionic acid 2,2,2-trichloroethyl ester
• 英文别名: N-(tert-butoxycarbonyl)-3-(3-chloro-4-methoxyphenyl)-D-alanine 2,2,2-trichloroethyl ester；2,2,2-trichloroethyl (2R)-3-(3-chloro-4-methoxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
• 化学式: C₁₇H₂₁Cl₄NO₅
• 分子量: 461.169
• InChiKey: KOXHQMBPYKPFBD-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  27
• 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：
  73.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  2,2,2-三氯乙醇 、 N-Boc-O-methyl-D-3-chlorotyrosine 在 吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以65%的产率得到(R)-2-tert-butoxycarbonylamino-3-(3-chloro-4-methoxyphenyl)propionic acid 2,2,2-trichloroethyl ester
  参考文献：
  名称：

  隐藻素的全合成。隐藻素 A 和 C 结构的修订

  摘要：

  描述了隐霉素 C 和 D 的收敛全合成。已经表明，在两种天然产物中，α-氨基酸的绝对构型对应于 D 系列。已更正了隐藻素 C 的结构分配以反映这一事实。由于隐藻素A的结构与隐藻素C相关，隐藻素A中的氯-0-甲基酪氨酸单元具有D-构型。隐藻素是与陆生蓝绿藻 Nostoc sp. 相关的强效肿瘤选择性细胞毒素。GSV 224' 和 Nostoc sp。ATCC 53789.2 每种藻类中的主要细胞毒素，cryptophycin A，对植入小鼠的实体瘤（包括耐药性肿瘤）显示出极好的活性。超过 20 种相关的细胞毒素作为次要成分存在于 GSV 224 菌株中，以及这些化合物中的一些，例如，隐藻素 B 和 C，已被分离出足够的量用于体内评估。~为了获得足够数量的选定天然存在的隐藻素和合成类似物，用于构效关系 (SAR) 研究、临床前评估和人类临床试验，我们设计了一个通用的合成。正如原始论文中所述，Cryptophycins

  DOI：

  10.1021/ja00114a011

文献信息

• 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
• Total Synthesis of Cryptophycins. Revision of the Structures of Cryptophycins A and C
  作者：Russell A. Barrow、Thomas Hemscheidt、Jian Liang、Seunguk Paik、Richard E. Moore、Marcus A. Tius

  DOI：10.1021/ja00114a011

  日期：1995.3

  The convergent total synthesis of cryptophycins C and D is described. It has been shown that in both natural products the absolute configuration of the a-amino acid corresponds to the D-series. The structural assignment for cryptophycin C has been corrected to reflect this fact. Since the structure of cryptophycin A has been correlated to cryptophycin C, the chloro-0-methyltyrosine unit in cryptophycin

  描述了隐霉素 C 和 D 的收敛全合成。已经表明，在两种天然产物中，α-氨基酸的绝对构型对应于 D 系列。已更正了隐藻素 C 的结构分配以反映这一事实。由于隐藻素A的结构与隐藻素C相关，隐藻素A中的氯-0-甲基酪氨酸单元具有D-构型。隐藻素是与陆生蓝绿藻 Nostoc sp. 相关的强效肿瘤选择性细胞毒素。GSV 224' 和 Nostoc sp。ATCC 53789.2 每种藻类中的主要细胞毒素，cryptophycin A，对植入小鼠的实体瘤（包括耐药性肿瘤）显示出极好的活性。超过 20 种相关的细胞毒素作为次要成分存在于 GSV 224 菌株中，以及这些化合物中的一些，例如，隐藻素 B 和 C，已被分离出足够的量用于体内评估。~为了获得足够数量的选定天然存在的隐藻素和合成类似物，用于构效关系 (SAR) 研究、临床前评估和人类临床试验，我们设计了一个通用的合成。正如原始论文中所述，Cryptophycins
• 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.