(S)-benzyl 2-(but-3-enyl(1-phenylethyl)amino)acetate | 420840-10-4

• 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: (S)-benzyl 2-(but-3-enyl(1-phenylethyl)amino)acetate
• 英文别名: benzyl 2-[but-3-enyl-[(1S)-1-phenylethyl]amino]acetate
• CAS: 420840-10-4
• 化学式: C₂₁H₂₅NO₂
• 分子量: 323.435
• InChiKey: ZNPLWKSFSHQMSP-SFHVURJKSA-N

物化性质

• 沸点：
  417.2±40.0 °C(Predicted)
• 密度：
  1.060±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  24
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-benzyl 2-(but-3-enyl(1-phenylethyl)amino)acetate 在 乙酰氯 、 zinc dibromide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 生成 (2S,3S)-3-methyloxycarbonylmethyl-1-(1-phenylethyl)pyrrolidine-2-carboxylic acid benzyl ester
  参考文献：
  名称：

  不对称合成3-取代脯氨酸嵌合体，具有蛋白质氨基酸的极性侧链。

  摘要：

  氨基-锌-烯-烯酸酯环化反应是3-取代脯氨酸合成的直接途径。本文中我们报道了该反应在赖氨酸，谷氨酸，谷氨酰胺，精氨酸和丝氨酸脯氨酸嵌合体的合成中的应用。所有这些化合物均以对映体纯形式获得，并适当保护用于肽合成。

  DOI：

  10.1021/jo048762q
• 作为产物：
  描述：

  N-(3-butenyl)-N-[(S)-1-phenylethyl]amine 、 2-溴乙酸苄酯 在 sodium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以90%的产率得到(S)-benzyl 2-(but-3-enyl(1-phenylethyl)amino)acetate
  参考文献：
  名称：

  氨基-锌-烯醇盐碳金属化反应：应用于末端取代的烯烃的闭环反应，用于不对称合成顺式和反式3-脯氨酰亮氨酸。

  摘要：

  氨基锌烯醇盐环化反应是3-取代脯氨酸合成的直接途径。作为经典的分子内碳金属化反应，将锌加成至双键的适用性限于其中末端烯烃碳未被取代的底物。对合成顺式和反式3-脯氨酰亮氨酸衍生物感兴趣，以进行结构-活性关系（SAR）研究，我们集中精力通过末端取代的双键的氨基-锌-烯酸酯环化制备这些化合物。本文中我们报道活化基团例如环丙基与末端烯烃碳的连接使得末端取代的烯烃的氨基-锌-烯醇酸酯环化。反应是立体特异性的，导致反式3取代的脯氨酸衍生物，而在末端未取代的烯烃的氨基-锌-烯醇酸酯环化中观察到顺式立体化学。通过X射线分析，NMR和通过明确途径获得的顺式和反式衍生物的光学活性比较，确定了3-脯氨酰亮氨酸的绝对构型。

  DOI：

  10.1021/jo026535n

文献信息

• [EN] INDOLE COMPOUNDS OR ANALOGUES THEREOF USEFUL FOR THE TREATMENT OF AGE-RELATED MACULAR DEGENERATION (AMD)<br/>[FR] COMPOSÉS INDOLIQUES OU ANALOGUES DE CEUX-CI UTILES DANS LE TRAITEMENT DE LA DÉGÉNÉRESCENCE MACULAIRE LIÉE À L'ÂGE (DMLA)
  申请人：NOVARTIS AG

  公开号：WO2012093101A1

  公开（公告）日：2012-07-12

  The present invention provides a compound of formula (I): a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

  本发明提供了一种公式(I)的化合物：一种制造本发明化合物的方法及其治疗用途。本发明进一步提供了一种药物活性剂的组合物和一种药物组合物。
• Amino-Zinc-Ene-Enolate Cyclization: A Short Access to <i>cis</i>-3-Substituted Prolino-homotryptophane Derivatives
  作者：Céline Mothes、Solange Lavielle、Philippe Karoyan

  DOI：10.1021/jo801006a

  日期：2008.9.1

  Proline chimeras are useful tools for medicinal chemistry and/or biological applications. The asymmetric synthesis of cis-3-substituted prolines can be easily achieved via amino-zinc-ene-enolate cyclization followed by transmetalation of the cyclic zinc intermediate for further functionalization. Syntheses of prolino-homotryptophane derivatives were achieved through Negishi cross-coupling of the zinc

  脯氨酸嵌合体是用于药物化学和/或生物学应用的有用工具。顺式-3-取代的脯氨酸的不对称合成可通过氨基-锌-烯-烯酸酯环化，然后对环状锌中间体进行重金属化以进一步官能化来轻松实现。通过锌中间体与吲哚环的Negishi交叉偶联来实现脯氨酰-高色氨酸衍生物的合成。需要使用衍生自Fu的[（t-Bu3）PH] -BF4的Pd催化剂，以避免不希望的β-氢化物消除。获得易于用于肽合成的光学纯和正交保护的化合物。
• Complement pathway modulators and uses thereof
  申请人：ALTMANN Eva

  公开号：US20120295884A1

  公开（公告）日：2012-11-22

  The present invention provides a compound of formula I: a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

  本发明提供了一种化合物I的方法，用于制造本发明的化合物以及其治疗用途。本发明还提供了一种药理活性剂的组合和制药组合物。
• Development of a Zinc-Mediated Approach to a 2,3-<i>cis</i>-Pyrrolidine Arginase Inhibitor
  作者：Thomas W. Lyons、Theodore A. Martinot、Cyndi Qixin He、Ji Qi、Guangxin Shao

  DOI：10.1021/acs.oprd.0c00171

  日期：2020.8.21

  This manuscript outlines the development activities toward a robust synthesis of cis-2,3-pyrrolidine via tandem zincenolate cyclization/Negishi coupling that proceeds with high diastereoselectivity. The methodology facilitated a gram-scale delivery of the target API and eliminated the need for costly chiral resolutions and inefficient protecting group manipulations. A series of DFT experiments provided a transition-state model that agrees closely with the experimental observations and provides a more in-depth understanding of the observed selectivity.
• Synthesis and Evaluation of Analogues of <i>N</i>-Phthaloyl-<scp>l</scp>-tryptophan (RG108) as Inhibitors of DNA Methyltransferase 1
  作者：Saâdia Asgatay、Christine Champion、Gaël Marloie、Thierry Drujon、Catherine Senamaud-Beaufort、Alexandre Ceccaldi、Alexandre Erdmann、Arumugam Rajavelu、Philippe Schambel、Albert Jeltsch、Olivier Lequin、Philippe Karoyan、Paola B. Arimondo、Dominique Guianvarc’h

  DOI：10.1021/jm401419p

  日期：2014.1.23

  DNA methyltransferases (DNMT) are promising drug targets in cancer provided that new, more specific, and chemically stable inhibitors are discovered. Among the non-nucleoside DNMT inhibitors, N-phthaloyl-L-tryptophan 1 (RG108) was first identified as inhibitor of DNMT1. Here, 1 analogues were synthesized to understand its interaction with DNMT. The indole, carboxylate, and phthalimide moieties were modified. Homologated and conformationally constrained analogues were prepared. The latter were synthesized from prolinohomotryptophan derivatives through a methodology based amino-zinc-ene-enolate cyclization. All compounds were tested for their ability to inhibit DNMT1 in vitro. Among them, constrained compounds 16-18 and NPys derivatives 10-11 were found to be at least 10-fold more potent than the reference compound. The cytotoxicity on the tumor, DU145 cell line of the most potent inhibitors was correlated to their inhibitory potency. Finally, docking studies were conducted in order to understand their binding mode. This study provides insights for the design of the next-generation of DNMT inhibitors.