methyl (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)pent-4-ynoate | 1063719-63-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: methyl (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)pent-4-ynoate
• 英文别名: (S)-methyl 2-(((9H-fluoren-9-yl)methoxy)carbonylamino)pent-4-ynoate；N-α-(((9H-fluoren-9-yl)methoxy)carbonyl)-L-propargylglycine methyl ester；(S)-N-Fmoc-α-propargylglycine methyl ester；(S)-Methyl 2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)pent-4-ynoate；methyl (2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)pent-4-ynoate
• CAS: 1063719-63-0
• 化学式: C₂₁H₁₉NO₄
• 分子量: 349.386
• InChiKey: ONXCTKJXSGEPHY-IBGZPJMESA-N

物化性质

• 熔点：
  128-129 °C(Solv: ethanol (64-17-5))
• 沸点：
  551.6±50.0 °C(Predicted)
• 密度：
  1.226±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 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：

  methyl (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)pent-4-ynoate 在 哌啶 、 ammonium hydroxide 、 铜 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 68.25h， 生成 4-(but-2-yn-1-yloxy)-N-((S)-3-(1-(((2R,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl) -3,4-dihydroxytetrahydrofuran-2-yl)methyl)-1H-1,2,3-triazol-4-yl)-1-(hydroxyamino)-1-oxopropan-2-yl)benzamide
  参考文献：
  名称：

  Propargylglycine-based antimicrobial compounds are targets of TolC-dependent efflux systems in Escherichia coli

  摘要：

  A library of novel L-propargylglycine-based compounds were designed and synthesized with the goal of inhibiting the growth of Gram-negative bacteria by targeting LpxC, a highly conserved Gram-negative enzyme which performs an essential step in the lipid A biosynthetic pathway. These compounds were designed with and without a nucleoside and had varying tail structures, which modulate their lipophilicity. The synthetic scheme was improved compared to previous methods: a methyl ester intermediate was converted to a hydroxamic acid, which obviated the need for a THP protecting group and improved the yields and purity of the final compounds. Antimicrobial activity was observed for non-nucleoside compounds containing a phenyl propargyl ether tail (5) or a biphenyl tail (6). An MIC of 16 mu g/mL was achieved for 6 in Escherichia coli, but inhibition was only possible in the absence of TolC-mediated efflux. Compound 5 had an initial MIC > 160 mu g/mL in E. coli. Enhancing outer membrane permeability or eliminating efflux reduced the MIC modestly to 100 mu g/mL and 80 mu g/mL, respectively. These results highlight the importance of hydrophobicity of this class of compounds in developing LpxC inhibitors, as well as the design challenge of avoiding multidrug efflux activity.

  DOI：

  10.1016/j.bmcl.2019.126875
• 作为产物：
  描述：

  (2S)-2-氨基-4-戊炔酸 、 (9H-芴-9-基)甲基 2,5-二氧代吡咯烷-1-羧酸 在 4-二甲氨基吡啶 、 sodium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙二醇二甲醚 、 二氯甲烷 为溶剂， 生成 methyl (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)pent-4-ynoate
  参考文献：
  名称：

  α-炔丙基氨基酸衍生的光学活性新型取代聚乙炔：合成，二级结构和对离子的响应性

  摘要：

  新型旋光取代的乙炔HCCCH 2 CR 1（CO 2 CH 3）NHR 2 [（S）-/（R）-1：R 1 = H，R 2 = Boc，（S）-2：R 1 = CH 3，R 2 = Boc，（S）‐3：R 1 = H，R 2 = Fmoc，（S）‐4：R 1 = CH 3，R 2 = Fmoc（Boc =叔由α-炔丙基甘氨酸和α-炔丙基丙氨酸合成-丁氧基羰基，Fmoc = 9-芴基甲氧基羰基]，并与铑催化剂聚合，以高收率提供数均分子量为2400-38,900的聚合物。极化，圆二色性（CD），和紫外可见分光分析表明，聚[（小号） - 1 ]，聚[（[R ）- 1 ]，和聚[（小号- ）4形成的主要单手螺旋结构]在极性和非极性溶剂中均如此。带有未保护羧基的聚[（S）-1a ]是通过对聚[（S）-1 ]和聚[（通过使用哌啶去除聚[（S）-4 ]的Fmoc基团，可得到带有未保护氨基的S）-4b ]

  DOI：

  10.1002/pola.25975

文献信息

• Synthesis of non-proteinogenic phenylalanine derivatives by rhodium-catalyzed [2+2+2] cycloaddition reactions
  作者：Lídia Garcia、Anna Pla-Quintana、Anna Roglans

  DOI：10.1039/b910961g

  日期：——

  Non-proteinogenic phenylalanine derivatives were efficiently prepared by Rh(I)-catalyzed [2+2+2] cycloaddition reactions between enantiopure and racemic propargylglycine amino acids, with different protective groups, and diynes. Diverse substituents, including tags such as dansyl or dabsyl, were introduced onto the aromatic ring of the amino acid derivatives by selecting the most appropriate diyne

  通过Rh（I）催化的对映纯和具有不同保护基团的外消旋炔丙基甘氨酸氨基酸和二炔之间的Rh（I）催化的[2 + 2 + 2]环加成反应，可以有效地制备非蛋白质苯基丙氨酸衍生物。通过选择最合适的二炔反应伙伴，将包括标签如丹磺酰基或达布磺酰基在内的各种取代基引入到氨基酸衍生物的芳环上。
• Peptide-Directed Binding for the Discovery of Modulators of α-Helix-Mediated Protein-Protein Interactions: Proof-of-Concept Studies with the Apoptosis Regulator Mcl-1
  作者：Andrew Michael Beekman、Maria Anne O'Connell、Lesley Ann Howell

  DOI：10.1002/anie.201705008

  日期：2017.8.21

  molecules can be challenging owing to large, hydrophobic binding surfaces. Herein, we describe a strategy that exploits selective α-helical PPIs, transferring these characteristics to small molecules. The proof of concept is demonstrated with the apoptosis regulator Mcl-1, commonly exploited by cancers to avoid cell death. Peptide-directed binding uses few synthetic transformations, requires the production

  由于小分子的疏水性结合表面较大，因此用小分子靶向 PPI 可能具有挑战性。在此，我们描述了一种利用选择性 α-螺旋 PPI 的策略，将这些特性转移到小分子上。细胞凋亡调节因子 Mcl-1 证明了这一概念，癌症通常利用该调节因子来避免细胞死亡。肽定向结合使用很少的合成转化，需要产生少量的化合物，并且产生高百分比的命中。在本实施例中，约50%的制备小分子对Mcl-1的IC50值小于100μm，约25%的小分子的IC50值小于1μm。与其他抗凋亡蛋白相比，化合物对 Mcl-1 具有选择性，对癌细胞系具有细胞毒性，并诱导细胞凋亡的特征。这种方法代表了一种快速发现新型 α-螺旋 PPI 调节剂的新颖且经济的过程。
• Accessing elusive σ-type cyclopropenium cation equivalents through redox gold catalysis
  作者：Xiangdong Li、Matthew D. Wodrich、Jérôme Waser

  DOI：10.1038/s41557-024-01535-8

  日期：2024.6

  cyclopropenyl-gold(III) species as equivalents of σ-type CPCs, which can then react with terminal alkynes and vinylboronic acids. With catalyst loadings as low as 2 mol%, the synthesis of highly functionalized alkynyl- or alkenyl-cyclopropenes proceeded under mild conditions. A class of hypervalent iodine reagents—the cyclopropenyl benziodoxoles (CpBXs)—enabled the direct oxidation of gold(I) to gold(III) with concomitant

  环丙烯是最小的不饱和碳环。从环丙烯中去除一个取代基可得到环丙烯阳离子（C3+ 系统，CPC）。1957 年，Breslow 通过去除脂肪族位点上的取代基发现了稳定的芳香族 π 型 CPC。相比之下，σ型 CPC（通过去除烯烃上的一个取代基正式获得）不稳定且相对未被探索。在这里，我们介绍了亲电环丙烯基金 （III） 物质作为 σ 型 CPC 的等价物，然后可以与末端炔烃和乙烯基硼酸反应。在催化剂负载量低至 2 mol% 的情况下，在温和条件下进行高度官能化的炔基或烯基环丙烯的合成。一类高价碘试剂——环丙烯基苯并氧唑 （CPBX）——能够直接将金 （I） 氧化成金 （III），同时发生环丙烯基团的转移。该方案是通用的，对许多官能团具有耐受性，可用于复杂天然产物、生物活性分子和药物的后期修饰。
• Preliminary investigations into triazole derived androgen receptor antagonists
  作者：Jarrad M. Altimari、Birunthi Niranjan、Gail P. Risbridger、Stephanie S. Schweiker、Anna E. Lohning、Luke C. Henderson

  DOI：10.1016/j.bmc.2014.03.018

  日期：2014.5

  A range of 1,4-substituted-1,2,3-N-phenyltriazoles were synthesized and evaluated as non-steroidal androgen receptor (AR) antagonists. The motivation for this study was to replace the N-phenyl amide portion of small molecule antiandrogens with a 1,2,3-triazole and determine effects, if any, on biological activity. The synthetic methodology presented herein is robust, high yielding and extremely rapid. Using this methodology a series of 17 N-aryl triazoles were synthesized from commercially available starting materials in less than 3 h. After preliminary biological screening at 20 and 40 mu M, the most promising three compounds were found to display IC50 values of 40-50 mu M against androgen dependent (LNCaP) cells and serve as a starting point for further structure-activity investigations. All compounds in this work were the focus of an in silico study to dock the compounds into the human androgen receptor ligand binding domain (hARLBD) and compare their predicted binding affinity with known antiandrogens. A comparison of receptor-ligand interactions for the wild type and T877A mutant AR revealed two novel polar interactions. One with Q738 of the wild type site and the second with the mutated A877 residue. (C) 2014 Elsevier Ltd. All rights reserved.
• Enyne Metathesis/Brønsted Acid-Promoted Heterocyclization
  作者：Kyle P. Kalbarczyk、Steven T. Diver

  DOI：10.1021/jo802582k

  日期：2009.3.6

  The "one-pot" synthesis of nitrogen heterocycles and an oxygen heterocycle by enyne metathesis and in situ cyclization is reported.