ethyl (2E,4S)-4-[(tert-butoxycarbonyl)amino]-5-phenylpent-2-enoate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl (2E,4S)-4-[(tert-butoxycarbonyl)amino]-5-phenylpent-2-enoate
• 英文别名: ethyl (S,E)-4-((tert-butoxycarbonyl)amino)-5-phenylpent-2-enoate；(S,E)-ethyl 4-((tert-butoxycarbonyl)amino)-5-phenylpent-2-enoate；(E)-4-tert-butoxycarbonylamino-5-phenyl-pent-2-enoic acid ethyl ester；ethyl (E,4S)-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-phenylpent-2-enoate
• 化学式: C₁₈H₂₅NO₄
• 分子量: 319.401
• InChiKey: OFLTYWJABWDXRC-AYJWMTRPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 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：

  ethyl (2E,4S)-4-[(tert-butoxycarbonyl)amino]-5-phenylpent-2-enoate 在 4-二甲氨基吡啶 、 水 、 三乙酰氧基硼氢化钠 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 128.0h， 生成 (E)-[4-(1-benzyl-3-methylcarbamoylallylcarbamoyl)-4-isopropylaminobutylamino]acetic acid benzyl ester
  参考文献：
  名称：

  Anti-malarial activity of new N-acetyl-l-leucyl-l-leucyl-l-norleucinal (ALLN) derivatives against Plasmodium falciparum

  摘要：

  Malaria is the most common of the parasitic diseases in tropical and subtropical regions. Adverse side effects of anti-malarial drugs have precluded them as a potential clinical drug. In this study, novel derivatives of N-acetyl-L-leucyl-L-leucyl-L-norleucinal (ALLN) based on a variety of dipeptidyl alpha,beta-unsaturated amides containing lysine as a part were synthesized and evaluated. Lower toxicity was achieved by reducing or eliminating the tendency of forming chemically reactive and toxic intermediates and metabolites. The synthesized compounds were evaluated for anti-malarial efficacy against Plasmodium falciparum and cytotoxicity in human epitheloid carcinoma cervix (HeLa cells) by estimating the therapeutic index (TI). N-Methyl amide with N'-Boc protection among them exhibited strong anti-malarial activity and N-methyl amide with N'-m-methylbenzyl amide showed excellent anti-malarial activity with much lower toxicity than the ALLN. Therefore, the two chemicals, as well as the underlying design rationale, could be useful in the discovery and development of new anti-malarial drugs. (c) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.12.100
• 作为产物：
  描述：

  BOC-PHE-甲氧基甲胺 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 ethyl (2E,4S)-4-[(tert-butoxycarbonyl)amino]-5-phenylpent-2-enoate
  参考文献：
  名称：

  Synthesis of α, β-unsaturated γ-amino esters with unprecedented high (E)-stereoselectivity and their conformational analysis in peptides

  摘要：

  描述了一种温和、高效且无光学异构化的N保护α, β-不饱和γ-氨基酯的合成方法，该方法具有前所未有的高E型立体选择性。该方法与Boc、Fmoc及其他侧链保护基团相容。研究了单体和同源及混合二肽中乙烯基γ-氨基酯的晶体构象。此外，乙烯基同源二肽显示出β-折叠构象，而混合的α型和α,β-不饱和γ-杂合二肽在单晶中适应了不规则结构。

  DOI：

  10.1039/c1ob05732d

文献信息

• Efficient synthesis of functionalized olefins by Wittig reaction using Amberlite resin as a mild base
  作者：Tushar R. Valkute、Eswar K. Aratikatla、Asish K. Bhattacharya

  DOI：10.1080/00397911.2016.1276191

  日期：2017.3.19

  convenient procedure for the synthesis of olefins by the reaction of stabilized, semistabilized, and nonstabilized phosphorous ylides with various aldehydes or ketone using Amberlite resin as a mild base is described. Our developed method offers facile and racemization-free synthesis of α,β-unsaturated amino esters and chiral allylic amine. The developed methodology offers mild reaction conditions, high efficiency

  摘要描述了使用 Amberlite 树脂作为弱碱，通过稳定、半稳定和不稳定的磷叶立德与各种醛或酮反应合成烯烃的简便方法。我们开发的方法提供了 α,β-不饱和氨基酯和手性烯丙胺的简便且无外消旋的合成。所开发的方法提供温和的反应条件、高效率和最终产品的容易分离，是已知程序的实用替代方案。图形概要
• Design and synthesis of a novel class of furan-based molecules as potential 20S proteasome inhibitors
  作者：Yiqiu Fu、Bo Xu、Xiaomin Zou、Chao Ma、Xiaoming Yang、Ke Mou、Gang Fu、Yang Lü、Ping Xu

  DOI：10.1016/j.bmcl.2006.11.020

  日期：2007.2

  A novel class of furan-based compounds as potential 20S proteasome inhibitors have been designed and synthesized, among which nine compounds are peptide derivatives and six molecules are statine peptidomimetics. The C-terminal furanyl moiety was introduced to target molecules as furan-based amino acids. All the compounds were obtained steadily with moderate to high yield. Compound 12 was a selective

  已经设计和合成了一类新型的呋喃基化合物作为潜在的20S蛋白酶体抑制剂，其中九种化合物是肽衍生物，六种分子是他汀类肽模拟物。将C末端呋喃基部分作为基于呋喃的氨基酸引入靶分子。稳定地获得了所有化合物，产率中等至高。化合物12是选择性的中度有效的蛋白酶体拟肽抑制剂。它有效地抑制了HepG2和HL-60的增殖。
• Synthesis and biological activity of cyclolinopeptide A analogues modified with γ 4 -bis(homo-phenylalanine)
  作者：Karol Jędrzejczak、Paweł Hrynczyszyn、Małgorzata Szczesio、Jolanta Artym、Tomasz Jastrząbek、Maja Kocięba、Marek Główka、Krzysztof Huben、Iwona Kochanowska、Michał Zimecki、Janusz Zabrocki、Stefan Jankowski、Beata Kolesińska

  DOI：10.1016/j.bmc.2017.05.063

  日期：2017.8

  γ-peptides with a dominance of an antiparallel arrangement. As carbonyl groups may be engaged in the interactions with plausible receptors through hydrogen bonds, a similar biological activity of the modified peptides was expected. Our biological studies showed that certain cyclic, but not the corresponding linear peptides, lowered the viability of peripheral blood mononuclear cells (PBMC) at 100 μg/mL concentration

  环亚麻肽A（CLA），由亚麻种子衍生的免疫抑制九肽，用改性小号或- [R -γ 4中的位置3或4双（同型苯丙氨酸），或两者3个4这些修饰改变的新的类似物的灵活性和分子内氢键的分布。类似物11 C（临1 -Pro 2 -Phe 3 - S- γ 4 - hhPhe 4 -Leu 5 -Ile 6 -Ile 7 -Leu 8 -Val 9），13 C（临1 -Pro 2-小号-γ 4 - hhPhe 3 - [R -γ 4 - hhPhe 4 -Leu 5 -Ile 6 -Ile 7 -Leu 8 -Val 9）和15 C（临1 -Pro 2 - [R - γ 4 - hhPhe 3 - Phe 4 -Leu 5 -Ile 6 -Ile 7 -Leu 8 -Val 9）以稳定的顺式/反式混合物存在Pro-Pro肽键的异构体。对两个羰基（相邻的γ-氨基酸）的晶体状态的相对空间取向的比较显示出与α-肽的构象相似性。-CH
• Synthesis of Enantiomerically Pure 3-Substituted Piperazine-2-acetic Acid Esters as Intermediates for Library Production
  作者：Shiva Krishna Reddy Guduru、Srinivas Chamakuri、Idris O. Raji、Kevin R. MacKenzie、Conrad Santini、Damian W. Young

  DOI：10.1021/acs.joc.8b01708

  日期：2018.10.5

  substitutions, leaving the four carbon atoms underutilized. Using an efficient six-step synthesis, chiral amino acids were transformed into 3-substituted piperazine-2-acetic acid esters as diastereomeric mixtures whose cis and trans products (dr 0.56 → 2.2:1, respectively) could be chromatographically separated. From five amino acids (both antipodes) was obtained a complete matrix of 20 monoprotected chiral 2

  哌嗪杂环在FDA批准的药物和生物活性化合物中得到广泛利用，但其化学多样性通常仅限于环氮取代，从而使四个碳原子未被充分利用。使用高效的六步合成方法，将手性氨基酸转化为3-取代的哌嗪-2-乙酸酯，为非对映异构体混合物，其色谱图可分离出顺式和反式产物（分别为dr 0.56→2.2：1）。从五个氨基酸（均为对映体）获得了20个单保护的手性2，3-二取代的哌嗪的完整基质，每种均作为单个绝对立体异构体，但均以克数表示。与构建更多Csp 3的总体目标保持一致这些丰富多样的哌嗪具有丰富的用于药物发现的化合物库，可以在两个氮原子上官能化，使其可用作平行库合成的支架，并用作生产新型哌嗪化合物的中间体。
• Peptidomimetic Vinyl Heterocyclic Inhibitors of Cruzain Effect Antitrypanosomal Activity
  作者：Bala C. Chenna、Linfeng Li、Drake M. Mellott、Xiang Zhai、Jair L. Siqueira-Neto、Claudia Calvet Alvarez、Jean A. Bernatchez、Emily Desormeaux、Elizabeth Alvarez Hernandez、Jana Gomez、James H. McKerrow、Jorge Cruz-Reyes、Thomas D. Meek

  DOI：10.1021/acs.jmedchem.9b02078

  日期：2020.3.26

  disease. We describe here a new series of reversible, but time-dependent, inhibitors of cruzain, composed of a dipeptide scaffold appended to vinyl-heterocycles meant to provide replacements for the irreversible reactive "warheads" of vinyl sulfone inactivators of cruzain. Peptidomimetic vinyl-heterocyclic inhibitors (PVHIs) containing Cbz-Phe-Phe/homoPhe- scaffolds with vinyl-2-pyrimidine, vinyl-2-pyridine

  Cruzain是一种寄生虫原生动物Trypanosoma cruzi的必需半胱氨酸蛋白酶，是恰加斯病的重要药物靶标。我们在这里描述了一系列新的可逆但时间依赖性的克鲁赞蛋白酶抑制剂，该抑制剂由附加至乙烯基杂环的二肽支架组成，旨在为克鲁赞蛋白酶的乙烯基砜灭活剂提供不可逆的反应性“弹头”。含Cbz-Phe-Phe / homoPhe-骨架并带有乙烯基-2-嘧啶，乙烯基-2-吡啶和乙烯基-2-（N-甲基）-吡啶基的拟肽乙烯基杂环抑制剂（PVHI）赋予了可逆的，时间依赖性的抑制克鲁萨因（Ki * = 0.1-0.4μM）。与人类组织蛋白酶B，L和S相比，这些Cruzain抑制剂显示出中等至出色的选择性，并且对人细胞没有明显的毒性，但在布鲁氏锥虫锥虫的细胞培养中有效（EC50 = 1-15μM），并在感染的小鼠心肌成纤维细胞中消除了克鲁氏锥虫（EC50 = 5-8μM）。PVHIs是一类新的Cruza