benzyl ((S)-1-(((S)-1-hydroxy-3-phenylpropan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate | 17224-88-3

• 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: benzyl ((S)-1-(((S)-1-hydroxy-3-phenylpropan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate
• 英文别名: 1-Propanol, (2S)-2-[N-(benzyloxycarbonyl-(R)-phenylalanyl)amino]-3-phenyl-；benzyl N-[(2S)-1-[[(2S)-1-hydroxy-3-phenylpropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamate
• CAS: 17224-88-3
• 化学式: C₂₆H₂₈N₂O₄
• 分子量: 432.519
• InChiKey: UQRYFUIRUGFGQJ-ZEQRLZLVSA-N

物化性质

• 沸点：
  700.9±60.0 °C(Predicted)
• 密度：
  1.204±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  32
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  87.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzyl ((S)-1-(((S)-1-hydroxy-3-phenylpropan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate 在 palladium dichloride 吡啶 、 氢氧化钾 、 sodium hydroxide 、 氢气 作用下， 以 乙醇 为溶剂， 反应 16.0h， 生成 苯甲酰-DL-苯丙氨酸
  参考文献：
  名称：

  Concerning the crude drug "Ti-ku-'pi." 1. Isolation and structure of lycium amide, a new dipeptide.

  摘要：

  一种新的二肽——枸杞酰胺（1）从中国的粗药“提库皮”中分离获得，该药材为枸杞（Solanaceae）的根皮。通过光谱法、化学降解和合成证明其结构为N-苯甲酰-L-苯丙氨酸-L-苯丙氨醇O-醋酸酯（1）。

  DOI：

  10.1248/cpb.32.3584
• 作为产物：
  描述：

  L-苯丙氨醇 、 N-苄氧羰基-L-苯丙氨酸 在 N-甲基吗啉 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 为溶剂， 反应 16.08h， 以96%的产率得到benzyl ((S)-1-(((S)-1-hydroxy-3-phenylpropan-2-yl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate
  参考文献：
  名称：

  新型手性双齿羟烷基-N-杂环卡宾配体的合成及其在钯催化的Mizoroki-Heck偶联中和二乙基锌不对称加成到苯甲醛中的应用

  摘要：

  的新的手性二齿羟咪唑鎓盐甲小库1是在多克规模方便地合成由廉价和可商购的手性池氨基酸。在咪唑罗基-赫克偶联反应中测试了由咪唑鎓盐1的去质子化生成的相应碳烯与氯化钯（II）的结合。在较低的催化剂负载量下，在产率和反应性方面获得了最显着的结果。在将二乙基锌不对称加成到苯甲醛中，还研究了这些咪唑鎓盐的催化活性。MgO纳米颗粒作为添加剂与这些配体结合使用在提高这些反应效率方面起着至关重要的作用。

  DOI：

  10.1016/j.tetlet.2013.11.027

文献信息

• Synthesis of Novel Chiral Diamino Alcohols and Their Application in Copper-Catalyzed Asymmetric Allylic Oxidation of Cycloolefins
  作者：Laleh Faraji、Saadi Samadi、Khosrow Jadidi、Behrouz Notash

  DOI：10.5012/bkcs.2014.35.7.1989

  日期：2014.7.20

  development of biologically active compounds. Moreover, the chiral diamino alcohols, 1, can be used in the asymmetrical reactions as a catalyst to increase reaction rate and as a chiral auxiliary or chiral ligand to induce the chirality in the synthesis of chiral products. Enantioselective allylic oxidation of olefins using copper chiral complexes have been the subject of great interest during the

  旋光氨基醇是一类重要的化合物，因为它们存在于天然产物中。他们还发现了作为手性配体和助剂的应用，用于各种不对称反应。此外，二氨基醇及其羟基二酰胺前体尤其是许多药物化合物的核心单元，例如 HIV 蛋白酶抑制剂 A80987 (3)、A77003 (4) 和拉考沙胺 (5)（方案 1）。由于手性羟基二酰胺、手性氨基醇及其甲氧基类似物的重要性和高效性，我们的注意力集中在开发一种简单有效的方法来生产一个小的对映体纯二氨基醇 1 及其羟基二酰胺前体 2 库。可用的起始材料。尽管邻氨基醇的不对称合成已被广泛研究，但关于二氨基醇的不对称合成的报道较少，二氨基醇可能成为新型氨基醇化合物的前体。手性羟基二酰胺 2 在结构上与分子 3-5 相似，有望为生物活性化合物的开发提供更多机会。此外，手性二氨基醇 1 可在不对称反应中用作催化剂以提高反应速率，并可用作手性助剂或手性配体以诱导手性产物合成中的手性。在过去十
• Synthesis and biological evaluation of N -(carbobenzyloxy)- l -phenylalanine and N -(carbobenzyloxy)- l -aspartic acid- β -benzyl ester derivatives as potent topoisomerase IIα inhibitors
  作者：Xiaoyan Han、Yifan Zhong、Guan Zhou、Hui Qi、Shengbin Li、Qiang Ding、Zhenming Liu、Yali Song、Xiaoqiang Qiao

  DOI：10.1016/j.bmc.2017.03.065

  日期：2017.6

  A new series of thirteen N-(carbobenzyloxy)-l-phenylalanine and N-(carbobenzyloxy)-l-aspartic acid-β-benzyl ester compounds were synthesized and evaluated for antiproliferative activity against four different human cancer cell lines: cervical cancer (HeLa), lung cancer (A549), gastric cancer (MGC-803) and breast cancer (MCF-7) as well as topoisomerase I and IIα inhibitory activity. Compounds (5a, 5b

  合成了一系列新的十三种N-（羰基苄氧基）-1-苯丙氨酸和N-（羰基苄氧基）-1-天冬氨酸-β-苄基酯化合物，并评估了其对四种不同的人类癌细胞系的抗增殖活性：宫颈癌（HeLa ），肺癌（A549），胃癌（MGC-803）和乳腺癌（MCF-7）以及拓扑异构酶I和IIα的抑制活性。化合物（5a，5b，5e，8a，8b）显示出显着的抗增殖活性，并且对四种癌细胞系的IC50值较低。同样，化合物5a，5b，5e，5f，8a，8d，8e和8f在100μM处显示拓扑异构酶IIα抑制活性，而5b，5e，8f与100μM和20μM的阳性对照分别显示潜在的拓扑异构酶IIα抑制活性。相反地​​，化合物5e，5f，与100μM的阳性对照相比，5g和8a显示出较弱的拓扑异构酶I抑制活性。化合物5b在低浓度时表现出最有效的拓扑异构酶IIα抑制活性，并且对四种人类癌细胞系表现出更好的抗增殖活性。通过分子对接进一步研究化合
• Highly Enantioselective Construction of Fluoroalkylated Quaternary Stereocenters via Organocatalytic Dehydrated Mannich Reaction of Unprotected Hemiaminals with Ketones
  作者：Sheng Zhang、Lijun Li、Yanbin Hu、Yanan Li、Yu Yang、Zhenggen Zha、Zhiyong Wang

  DOI：10.1021/acs.orglett.5b02514

  日期：2015.10.16

  organocatalytic asymmetric dehydrated Mannich reaction of fluoroalkyl hemiaminals with ketones is reported. In this Mannich reaction, previously less explored aryl ketones showed great reactivity. By virtue of this efficient method, a wide range of biologically active β-amino ketones were directly obtained. More importantly, two different intermediates involved in the reaction were detected and identified by 19F

  报道了氟代烷基半缩醛与酮的一般有机催化不对称脱水曼尼希反应。在该曼尼希反应中，以前较少探索的芳基酮显示出很高的反应活性。通过这种有效的方法，直接获得了广泛的生物活性β-氨基酮。更重要的是，通过19 F NMR和HRMS分析检测并鉴定了参与反应的两种不同中间体。此外，通过生物活性的氟烷基β-氨基醇的合成证明了产物的合成效用。
• Design and synthesis of new N-(fluorenyl-9-methoxycarbonyl) (Fmoc)-dipeptides as anti-inflammatory agents
  作者：Chiao-Ting Yen、Tsong-Long Hwang、Yang-Chang Wu、Pei-Wen Hsieh

  DOI：10.1016/j.ejmech.2008.11.008

  日期：2009.5

  Twenty-four new dipeptide analogs (1-24) of aurantiamide acetate were designed, synthesized, and assayed for effects on superoxide anion generation and elastase release by human neutrophils in response to fMLP/CB. Among them, seven N-(fluorenyl-9-methoxycarbonyl) (Fmoc)-dipeptides (6, 9,12, 14, 17, 18 and 20) showed potent inhibitory effects. Compounds 9 and 18 showed the most selective effects against human neutrophil elastase release, with IC50 values of 0.8+/-0.1 and 1.7+/-0.6 mu M, respectively, and were 130-fold more potent than phenylmethylsulfonyl fluoride (PMSF), the positive control, in this anti-inflammatory assay. These two compounds could be developed as new lead antiinflammatory agents. (C) 2008 Elsevier Masson SAS. All rights reserved.
• Development of α-keto-based inhibitors of cruzain, a cysteine protease implicated in Chagas disease
  作者：Youngchool Choe、Linda S. Brinen、Mark S. Price、Juan C. Engel、Meinolf Lange、Corinna Grisostomi、Scott G. Weston、Peter V. Pallai、Hong Cheng、Larry W. Hardy、David S. Hartsough、Marsha McMakin、Robert F. Tilton、Carmen M. Baldino、Charles S. Craik

  DOI：10.1016/j.bmc.2004.12.053

  日期：2005.3

  Trypanosoma cruzi, a protozoan parasite, is the causative agent of Chagas disease, a major cause of cardiovascular disease in many Latin American countries. There is an urgent need to develop an improved therapy due to the toxicity of existing drugs and emerging drug resistance. Cruzain, the primary cysteine protease of T cruzi, is essential for the survival of the parasite in host cells and therefore is an important target for the development of inhibitors as potential therapeutics. A novel series of alpha-ketoamide-, alpha-ketoacid-, alpha-ketoester-, and aldehyde-based inhibitors of cruzain has been developed. The inhibitors were identified by screening protease targeted small molecule libraries and systematically optimizing the P1, P2, P3, and P1 ' residues using specific structure-guided methods. A total of 20 compounds displayed picomolar potency in in vitro assays and three inhibitors representing different alpha-keto-based inhibitor scaffolds demonstrated anti-trypanosomal activity in cell culture. A 2.3 angstrom crystallographic structure of cruzain bound with one of the alpha-ketoester analogs is also reported. The structure and kinetic assay data illustrate the covalent binding, reversible inhibition mechanism of the inhibitor. Information on the compounds reported here will be useful in the development of new lead compounds as potential therapeutic agents for the treatment of Chagas disease and as biological probes to study the role that cruzain plays in the pathology. This study also demonstrates the validity of structure-guided approaches to focused library design and lead compound optimization. (c) 2005 Elsevier Ltd. All rights reserved.