trans-N-(benzyloxycarbonyl)-4-carboxy-L-proline dimethyl ester | 130830-70-5

• 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: trans-N-(benzyloxycarbonyl)-4-carboxy-L-proline dimethyl ester
• 英文别名: N-(benzyloxycarbonyl)-trans-4-carboxy-L-proline dimethyl ester；2,4-Dimethyl 1-(phenylmethyl) (2S,4R)-1,2,4-pyrrolidinetricarboxylate；1-O-benzyl 2-O,4-O-dimethyl (2S,4R)-pyrrolidine-1,2,4-tricarboxylate
• CAS: 130830-70-5
• 化学式: C₁₆H₁₉NO₆
• 分子量: 321.33
• InChiKey: VFLKUGOZEYYCCP-OLZOCXBDSA-N

物化性质

• 沸点：
  438.1±45.0 °C(Predicted)
• 密度：
  1.268±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  82.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  trans-N-(benzyloxycarbonyl)-4-carboxy-L-proline dimethyl ester 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 25.0 ℃ 、344.73 kPa 条件下， 反应 16.5h， 生成 Mosher amide of trans-4-carboxy-L-proline dimethyl ester
  参考文献：
  名称：

  Conformationally defined neurotransmitter analogs. Selective inhibition of glutamate uptake by one pyrrolidine-2,4-dicarboxylate diastereomer

  摘要：

  In order to determine the conformational requirements for binding of L-glutamate to the proteins involved in the process of neurotransmission, rigid analogues containing an embedded glutamate moiety have been prepared. These ''conformer mimics'', the pyrrolidine-2,4-dicarboxylates 4, 7, 11, and 14, were synthesized from commercially available trans-4-hydroxy-L-proline and cis-4-hydroxy-D-proline, and then were tested for their ability to inhibit the high-affinity transport of [H-3]-L-glutamate into synaptosomes and to block the binding of radioligands to the NMDA (N-methyl-D-aspartate), KA (kainate), and QA (quisqualate) glutamate neurotransmitter receptor sites. While none of the four analogues binds effectively to the excitatory receptors, the L-trans-isomer 7 is a potent and selective competitive inhibitor of L-glutamate transport. These results delineate a specific structural/conformational preference for binding to the uptake system that is distinct from that required for binding to the NMDA, KA, and QA receptors.

  DOI：

  10.1021/jm00106a037
• 作为产物：
  描述：

  (2S,4S)-1-(苄基羰基)-4-羟基吡咯烷-2-羧酸 在 吡啶 、 盐酸 、 对甲苯磺酸 作用下， 以 氯仿 、 二甲基亚砜 为溶剂， 反应 303.0h， 生成 trans-N-(benzyloxycarbonyl)-4-carboxy-L-proline dimethyl ester
  参考文献：
  名称：

  Conformationally defined neurotransmitter analogs. Selective inhibition of glutamate uptake by one pyrrolidine-2,4-dicarboxylate diastereomer

  摘要：

  In order to determine the conformational requirements for binding of L-glutamate to the proteins involved in the process of neurotransmission, rigid analogues containing an embedded glutamate moiety have been prepared. These ''conformer mimics'', the pyrrolidine-2,4-dicarboxylates 4, 7, 11, and 14, were synthesized from commercially available trans-4-hydroxy-L-proline and cis-4-hydroxy-D-proline, and then were tested for their ability to inhibit the high-affinity transport of [H-3]-L-glutamate into synaptosomes and to block the binding of radioligands to the NMDA (N-methyl-D-aspartate), KA (kainate), and QA (quisqualate) glutamate neurotransmitter receptor sites. While none of the four analogues binds effectively to the excitatory receptors, the L-trans-isomer 7 is a potent and selective competitive inhibitor of L-glutamate transport. These results delineate a specific structural/conformational preference for binding to the uptake system that is distinct from that required for binding to the NMDA, KA, and QA receptors.

  DOI：

  10.1021/jm00106a037

文献信息

• Proline–Glutamate Chimeras in Isopeptides. Synthesis and Biological Evaluation of Conformationally Restricted Glutathione Analogues
  作者：Mario Paglialunga Paradisi、Adriano Mollica、Ivana Cacciatore、Antonio Di Stefano、Francesco Pinnen、Anna Maria Caccuri、Giorgio Ricci、Silvestro Duprè、Alessandra Spirito、Gino Lucente

  DOI：10.1016/s0968-0896(03)00041-5

  日期：2003.4

  The two novel diastereoisomeric glutathione analogues I and 2 have been designed and synthesized by replacing the native gamma-glutamylic moiety with the conformational rigid skeleton of cis- or trans-4-carboxy-L-proline residue. Both analogues have been obtained by following the solution phase peptide chemistry methodologies and final reduction of the corresponding disulfide forms 13 and 14. The two analogues 1 and 2 have been tested towards gamma-glutamyltranspeptidase (gamma-GT) and human glutathione S-transferase (hGST P1-1). Both analogues 1 and 2 are completely resistant to enzymatic degradation by gamma-GT. The S-transferase utilizes the analogue 2 as a good substrate while is unable to bind the analogue 1. (C) 2003 Elsevier Science Ltd. All rights reserved.
• BRIDGES, RICHARD J.;STANLEY, MARK S.;ANDERSON, MICHAEL W.;COTMAN, CARL W.+, J. MED. CHEM., 34,(1991) N, C. 717-725
  作者：BRIDGES, RICHARD J.、STANLEY, MARK S.、ANDERSON, MICHAEL W.、COTMAN, CARL W.+

  DOI：——

  日期：——
• METHOD OF INHIBITING THE TRANSPORT OF L-GLUTAMATE
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：EP0497895A1

  公开（公告）日：1992-08-12
• US5942537A
  申请人：——

  公开号：US5942537A

  公开（公告）日：1999-08-24
• [EN] METHOD OF INHIBITING THE TRANSPORT OF L-GLUTAMATE
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：WO1991006536A1

  公开（公告）日：1991-05-16

  (EN) A method of inhibiting the transport of a neurotransmitter away from the synapse comprising contacting a neurotransmitter transporter with a compound having structure (I), wherein R1 = CO2H; -P(OH2); -SO3H; CO2R3; P(OR3)2; -SO3R; (a); or CONHR3 in any combination and wherein R2 = OR3, NR32, alkyl, or substituted alkyl and R3 = alkyl or substituted alkyl.(FR) Procédé d'inhibition du transport d'un neurotransmetteur en l'éloignant de la synapse, et consistant à mettre en contact un transporteur du neurotransmetteur avec un composé ayant la structure (I) dans laquelle R1 représente CO2H; -P(OH2); -SO3H; CO2R3; P(OR3)2; -SO3R; (a); ou CONHR3 dans n'importe quelle combinaison, et dans laquelle R2 représente OR3, NR32, alkyl, ou alkyl substitué et R3 représente alkyl ou alkyl substitué.