Z-L-Ala 2,2,2-trifluoroethyl ester | 203640-41-9

• 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: Z-L-Ala 2,2,2-trifluoroethyl ester
• 英文别名: Z-(S)-Ala-OCH2CF3；Z-L-Ala-OCH2CF3；Z-Ala-OCH2CF3；Cbz-L-Ala-OTfe；2,2,2-trifluoroethyl (2S)-2-(phenylmethoxycarbonylamino)propanoate
• CAS: 203640-41-9
• 化学式: C₁₃H₁₄F₃NO₄
• 分子量: 305.254
• InChiKey: QYXTWDMBWZEEJE-VIFPVBQESA-N

物化性质

• 沸点：
  368.6±42.0 °C(Predicted)
• 密度：
  1.286±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Z-L-Ala 2,2,2-trifluoroethyl ester 在 cross-linked enzyme aggregate of Alcalase 、 水 作用下， 反应 32.0h， 生成 苄氧羰基-L-丙氨酰-L-苯丙氨酸
  参考文献：
  名称：

  Enzymatic synthesis of activated esters and their subsequent use in enzyme-based peptide synthesis

  摘要：

  Chemoenzymatic peptide synthesis is potentially the most cost-efficient technology for the synthesis of short and medium-sized peptides. However, there are still some limitations when challenging peptides, e.g. containing sterically demanding acyl donors, non-proteinogenic amino acids or proline residues, are to be synthesized. To remedy these limitations, special ester moieties have been used that are specifically recognized by the enzyme, e.g. guanidinophenyl, carboxamidomethyl (Cam) or trifluoroethyl (Tfe) esters, which, unfortunately, are notoriously difficult to synthesize chemically. Herein, we demonstrate that Cam and Tfe esters are very useful for Alcalase-CLEA mediated peptide synthesis using sterically demanding and non-proteinogenic acyl donors as well as poor nucleophiles, and combinations thereof. Furthermore, these esters can be efficiently synthesized by using the lipase Cal-B or Alcalase-CLEA. Finally, it is shown that the ester synthesis by Cal-B and subsequent peptide synthesis by Alcalase-CLEA can be performed simultaneously using a two-enzyme-one-pot approach with glycolamide or 2,2,2-trifluoroethanol as additive. (C) 2011 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.molcatb.2011.03.012
• 作为产物：
  描述：

  2,2,2-三氟乙醇 、 苄氧羰基-L-丙氨酸 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 生成 Z-L-Ala 2,2,2-trifluoroethyl ester
  参考文献：
  名称：

  在动态控制的肽合成中，通过使用氨基甲酰基甲酯作为酰基供体，扩大了α-胰凝乳蛋白酶的底物耐受性

  摘要：

  在动力学控制方法中 肽 通过α-胰凝乳蛋白酶介导的合成，可通过切换蛋白酶来实现蛋白酶底物耐受性的扩大。 酰基供体从常规的甲酯到氨基甲酰基甲酯。因此，作为典型实例，通过使用固有不良的甲基酯获得极低的偶联效率。氨基酸 基质， 翼，通过使用此特殊功能得到了显着改善 酯。在其他氨基酸残基如Gly和Ser的偶联中也观察到其改善作用。羧基 成分。

  DOI：

  10.1039/b004180g

文献信息

• Superiority of the carbamoylmethyl ester as an acyl donor for the kinetically controlled amide-bond formation mediated by α-chymotrypsinElectronic supplementary information (ESI) available: elemental analyses and HPLC separation data. See http://www.rsc.org/suppdata/p1/b1/b108735p/
  作者：Toshifumi Miyazawa、Eiichi Ensatsu、Nobuhiro Yabuuchi、Ryoji Yanagihara、Takashi Yamada

  DOI：10.1039/b108735p

  日期：2002.1.23

  The superiority of the carbamoylmethyl ester as an acyl donor for the α-chymotrypsin-catalysed kinetically controlled peptide-bond formation is demonstrated in the couplings of an inherently poor amino acid substrate, Ala, with various amino acid residues as amino components and in the couplings of non-protein amino acids such as halogenophenylalanines as carboxylic components. Furthermore, this approach is applied to the amide-bond formation between an amino acid residue and a chiral amine, which is highly diastereoselective.

  研究表明，羰甲基氨基甲酸酯作为酰基供体在α-糜蛋白酶催化的动力学控制的肽键形成反应中具有优越性，这体现在天然不良氨基酸底物Ala与各种氨基酸残基作为氨基组分的偶联反应中，以及与非蛋白氨基酸如卤代苯丙氨酸作为羧基组分的偶联反应中。此外，这种方法还应用于氨基酸残基与手性胺之间的酰胺键形成反应，具有高度立体选择性。
• Pilot-Scale Lipase-Catalyzed Regioselective Acylation of Ribavirin in Anhydrous Media in the Synthesis of a Novel Prodrug Intermediate
  作者：Maria Tamarez、Brian Morgan、George S. K. Wong、Weidong Tong、Frank Bennett、Raymond Lovey、Jinping L. McCormick、Aleksey Zaks

  DOI：10.1021/op0255938

  日期：2003.11.1

  The ester 4 was synthesized via Candida antarctica lipase-catalyzed acylation of ribavirin (3) with the oxime ester of l-Cbz-Ala (2) in anhydrous THF. The reaction was highly regioselective, resulting in the exclusive acylation of the 5‘-hydroxyl. The process practiced on pilot-plant scale produced 82 kg of 4 in three batches in an average isolated yield of 82%.

  酯 4 是通过南极念珠菌脂肪酶催化的利巴韦林 (3) 与 l-Cbz-Ala (2) 在无水 THF 中的肟酯的酰化合成的。该反应是高度区域选择性的，导致 5'-羟基的唯一酰化。在中试规模上实施的工艺分三批生产 82 公斤 4，平均分离产率为 82%。
• Enzymatic synthesis and bioactivity of estradiol derivative conjugates with different amino acids
  作者：Ai-xin Yan、Robbie Y.K. Chan、Wai-Sum Lau、Kin-sing Lee、Man-Sau Wong、Guo-wen Xing、Gui-ling Tian、Yun-hua Ye

  DOI：10.1016/j.tet.2005.02.090

  日期：2005.6

  series of N-protected amino acid-estradiol derivative conjugates have been synthesized by coupling of 17β-aminoestra-1,3,5 (10)-trien-3-ol (1) or 17β-hydrazonoestra-1,3,5 (10)-trien-3-ol (2) with different amino acids via the catalysis of subtilisin Carlsberg in organic solvent. Various factors, including the structure of amino acid residue, different N-protecting groups of amino acids, different esters

  一系列ñ -保护的氨基酸雌二醇衍生物缀合物已经通过17β-aminoestra -1,3,5（10） -三烯-3-醇（的偶联合成1）或17β-hydrazonoestra -1,3,5（ 10）-trien-3-ol（2）通过枯草杆菌蛋白酶Carlsberg在有机溶剂中的催化作用而具有不同的氨基酸。各种因素，包括氨基酸残基的结构，不同的N系统地研究了氨基酸的保护基，不同的羧基酯和反应介质中水含量对酶促反应效率的影响。体外生物学活性研究表明，雌二醇衍生物结合物与雌激素受体之间的结合相互作用可能会受到结合氨基酸特性的影响，但结合特性改变的影响并没有导致MCF- 7和HeLa细胞系。
• Resolution of non-proteinogenic amino acids via microbial lipase-catalyzed enantioselective transesterification
  作者：Toshifumi Miyazawa、Motoe Mio、Yuko Watanabe、Takashi Yamada

  DOI：10.1139/v07-154

  日期：2008.3.1

  A number of non-proteinogenic amino acids bearing aliphatic side chains were resolved with moderate to good enantioselectivities (E = 15–42) through the Burkholderia cepacia lipase-catalyzed enantioselective transesterification of the 2,2,2-trifluoroethyl esters of their N-benzyloxycarbonyl derivatives with methanol as a nucleophile in diisopropyl ether.Key words: non-proteinogenic amino acids, microbial lipases, Burkholderia cepacia lipase, 2,2,2-trifluoroethyl ester, enantioselective transesterification, enantioselectivity.

  通过伯克霍尔德氏菌脂肪酶催化的2,2,2-三氟乙基酯的对映体选择性酯化反应，在二异丙基醚中以甲醇为亲核体，分离出了一些带有脂肪族侧链的非蛋白源氨基酸，其对映体选择性为中等到良好（E = 15-42）。关键词：非蛋白源氨基酸；微生物脂肪酶；伯克霍尔德氏菌脂肪酶；2,2,2-三氟乙基酯；对映选择性酯交换反应；对映选择性。
• Remarkable effects of donor esters on the α-chymotrypsin-catalyzed couplings of inherently poor amino acid substrates
  作者：Toshifumi Miyazawa、Kayoko Tanaka、Eiichi Ensatsu、Ryoji Yanagihara、Takashi Yamada

  DOI：10.1016/s0040-4039(97)10798-5

  日期：1998.2

  The extremely low efficiency during the α-chymotrypsin-catalyzed coupling of an inherently poor amino acid substrate, e.g., alanine, using the methyl ester as an acyl donor was significantly improved using esters such as the 2,2,2-trifluoroethyl or carbamoylmethyl ester. The ameliorating effect of the latter ester was especially significant.

  使用酯类（例如2,2,2-三氟乙基或氨基甲酰基甲基酯）可显着改善α-胰凝乳蛋白酶催化的固有不良氨基酸底物（如丙氨酸）在使用甲基酯作为酰基供体时的极低效率。后一种酯的改善作用特别显着。