(R)-benzyl 2-(but-3-enyl(1-phenylethyl)amino)acetate | 193538-82-8

• 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: (R)-benzyl 2-(but-3-enyl(1-phenylethyl)amino)acetate
• 英文别名: (R)-[but-3-enyl-(1-phenyl-ethyl)-amino]-acetic acid benzyl ester；benzyl 2-[but-3-enyl-[(1R)-1-phenylethyl]amino]acetate
• CAS: 193538-82-8
• 化学式: C₂₁H₂₅NO₂
• 分子量: 323.435
• InChiKey: ZNPLWKSFSHQMSP-GOSISDBHSA-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：

  (R)-benzyl 2-(but-3-enyl(1-phenylethyl)amino)acetate 在 盐酸 、 碳酸氢钠 、 lithium chloride 、 zinc dibromide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 1,2-二氯乙烷 为溶剂， 反应 198.58h， 生成 (2S,3S)-3-Methylsulfanylmethyl-pyrrolidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester
  参考文献：
  名称：

  Asymmetric synthesis of (2S,3S)- and (2S,3R)-3-prolinomethionines: 3-methylsulfanylmethyl-pyrrolidine-2-carboxylic acids

  摘要：

  The synthesis of 3-prolinomethionine can be easily achieved in a diastereoselective and enantioselective way via zinc-enolate cyclisation. After transmetallation by CuCN.2LiCl, the zinc-copper derivative was reacted with S-methyl methanesulfonothioate leading in a ''one-pot'' procedure, to N-(alpha-methylbenzyl)-3-prolinomethionine benzyl ester. The alpha-methylbenzyl group was transformed in vinyl-oxycarbonyl and tertiobutyloxycarbonyl groups successively. Reprotonation of cis Voc prolinomethionine enolate at low temperature yielded the enantiomerically pure trans diastereoisomer. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0957-4166(97)00203-6
• 作为产物：
  描述：

  (R)-N-(1-phenylethyl)but-3-en-1-amine 、 2-溴乙酸苄酯 在 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 生成 (R)-benzyl 2-(but-3-enyl(1-phenylethyl)amino)acetate
  参考文献：
  名称：

  Asymmetric synthesis of (2S,3S)- and (2S,3R)-3-prolinomethionines: 3-methylsulfanylmethyl-pyrrolidine-2-carboxylic acids

  摘要：

  The synthesis of 3-prolinomethionine can be easily achieved in a diastereoselective and enantioselective way via zinc-enolate cyclisation. After transmetallation by CuCN.2LiCl, the zinc-copper derivative was reacted with S-methyl methanesulfonothioate leading in a ''one-pot'' procedure, to N-(alpha-methylbenzyl)-3-prolinomethionine benzyl ester. The alpha-methylbenzyl group was transformed in vinyl-oxycarbonyl and tertiobutyloxycarbonyl groups successively. Reprotonation of cis Voc prolinomethionine enolate at low temperature yielded the enantiomerically pure trans diastereoisomer. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0957-4166(97)00203-6

文献信息

• 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。
• Thrombin inhibitors
  申请人：——

  公开号：US20040073025A1

  公开（公告）日：2004-04-15

  Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure Formula (I): wherein u is CH or N; Q is 1)—N(R 25 )CH(R 30 )—wherein the nitrogen atom is attached to R 1 , and R 25 and R 30 are independently selected from the group consisting of hydrogen, C 3-6 cycloalkyl, and C 1-6 alkyl, or 2) wherein the nitrogen atom is attached to R 1 , and m is 0, 1, or 2. 1

  本发明的化合物在抑制凝血酶和相关的血栓闭塞方面具有有用的结构式（I），其中u为CH或N；Q为1）-N（R25）CH（R30）-，其中氮原子连接到R1，且R25和R30分别选自氢，C3-6环烷基和C1-6烷基的群组，或2）其中氮原子连接到R1，且m为0，1或2.1。
• Amino-zinc-ene-enolate cyclisation: a short access to (2S,3R)- and (2S,3S)-3-benzylprolines (3-benzylpyrrolidine-2-carboxylic acids)
  作者：Jean Quancard、Hervé Magellan、Solange Lavielle、Gérard Chassaing、Philippe Karoyan

  DOI：10.1016/j.tetlet.2004.01.039

  日期：2004.3

  The synthesis of 3-benzylprolines can be easily achieved in a diastereoselective and enantioselective way via amino-zincene-enolate cyclisation. Transmetalation of the cyclic zinc intermediate with Pd-2(dba)(3)/P(o-Tolyl)(3) allowed functionalisation with an aromatic ring. One-pot hydrogenolysis and Boc-protection led to the cis-isomer readily usable for peptide synthesis. The transisomer was obtained by epimerisation of the alpha-centre in a sealed tue Lit 200 degreesC. (C) 2004 Elsevier Ltd. All rights reserved.
• US7144899B2
  申请人：——

  公开号：US7144899B2

  公开（公告）日：2006-12-05
• [EN] THROMBIN INHIBITORS<br/>[FR] INHIBITEURS DE THROMBINE
  申请人：MERCK & CO INC

  公开号：WO2002064559A2

  公开（公告）日：2002-08-22

  Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure Formula (I): wherein u is CH or N; Q is 1)-N(R?25)CH(R30¿)- wherein the nitrogen atom is attached to R?1, and R25 and R30¿ are independently selected from the group consisting of hydrogen, C¿3-6?cycloalkyl, and C1-6alkyl, or 2) wherein the nitrogen atom is attached to R?1¿, and m is 0, 1, or 2.