1-O-benzyl 2-O-methyl (4R)-4-hydroxy-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]pyrrolidine-1,2-dicarboxylate | 212387-68-3

• 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: 1-O-benzyl 2-O-methyl (4R)-4-hydroxy-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]pyrrolidine-1,2-dicarboxylate
• CAS: 212387-68-3
• 化学式: C₂₀H₂₇NO₇
• 分子量: 393.437
• InChiKey: PLZOWIMECWCUHA-IWPPFLRJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-O-benzyl 2-O-methyl (4R)-4-hydroxy-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]pyrrolidine-1,2-dicarboxylate 在 palladium on activated charcoal N-羟基-7-氮杂苯并三氮唑 、 氢气 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三苯基膦 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 偶氮二甲酸二乙酯 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 [(3S,7S,8aR)-3-Allyloxycarbonylmethyl-7-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-1,4-dioxo-hexahydro-pyrrolo[1,2-a]pyrazin-8a-yl]-acetic acid tert-butyl ester
  参考文献：
  名称：

  A template for the solid-phase synthesis of conformationally restricted protein loop mimetics

  摘要：

  三功能模板1由反式-4-羟基-L-脯氨酸和L-天冬氨酸合成，固定在固体载体上，用于固相合成含Asn-Pro-Asn-Ala（NPNA）模序的环状构象限制性六肽模拟物；NMR显示其在水溶液中形成稳定的β-转角构象。

  DOI：

  10.1039/cc9960002155
• 作为产物：
  描述：

  L-羟基脯氨酸 在 氯化亚砜 、 三乙胺 、 柠檬酸 、 lithium diisopropyl amide 作用下， 生成 1-O-benzyl 2-O-methyl (4R)-4-hydroxy-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]pyrrolidine-1,2-dicarboxylate
  参考文献：
  名称：

  A template for the solid-phase synthesis of conformationally restricted protein loop mimetics

  摘要：

  三功能模板1由反式-4-羟基-L-脯氨酸和L-天冬氨酸合成，固定在固体载体上，用于固相合成含Asn-Pro-Asn-Ala（NPNA）模序的环状构象限制性六肽模拟物；NMR显示其在水溶液中形成稳定的β-转角构象。

  DOI：

  10.1039/cc9960002155

文献信息

• Synthesis, Conformational Properties, and Immunogenicity of a Cyclic Template-Bound Peptide Mimetic Containing an NPNA Motif from the Circumsporozoite Protein of <i>Plasmodium </i><i>f</i><i>alciparum</i>
  作者：Christian Bisang、Luyong Jiang、Ernst Freund、Fabienne Emery、Christian Bauch、Hugues Matile、Gerd Pluschke、John A. Robinson

  DOI：10.1021/ja980444j

  日期：1998.8.1

  The immunodominant central portion of the circumsporozoite (CS) surface protein of the malaria parasite Plasmodium falciparum contains a tetrapeptide motif, Asn-Pro-Asn-Ala (NPNA), tandemly repeated almost 40 times. The three-dimensional structure of the CS protein, including the central repeat region, is presently unknown. We have investigated an approach to stabilize beta-turns in a single NPNA motif, by its incorporation into a template-bound cyclic peptide comprising the sequence ANPNAA. The template was designed to stabilize beta-turns in the peptide loop and to allow its conjugation to T-cell epitopes in a multiple antigen-peptide. NMR studies and MD simulations with time-averaged NOE-derived upper distance restraints support the formation of a stable beta-I turn conformation in the NPNA motif of this template-bound antigen. Balb/c mice immunized with a multiple-antigen-peptide containing four copies of the template-bound loop conjugated to a single universal T-cell epitope produced antibodies that bound P. falciparum sporozoites in immunofluorescence assays. These results provide further support for the immunological relevance of a type-I beta-turn conformation based on the NPNA cadence in the repeat region of the CS protein and illustrate the use of a novel template for the evaluation of conformationally constrained peptide immunogens.
• TEMPLATE-FIXED PEPTIDOMIMETICS WITH ANTIBACTERIAL ACTIVITY
  申请人：Vrijbloed Jan Wim

  公开号：US20100056432A1

  公开（公告）日：2010-03-04

  Template-fixed β-hairpin peptidomimetics of the general formula (I) wherein Z is a template-fixed chain of 12 α-amino acid residues which, depend on their positions in the chain (counted starting from the N-terminal amino acid) are Gly, or Pro, or of certain types which, as the remaining symbols in the above formula, are defined in the description and the claims, and salts thereof, have the property to selectively inhibit the growth of or to kill microorganisms such as Pseudomonas aeruginosa and Acinetobacter. They can be used as disinfectants for foodstuffs, cosmetics, medicaments or other nutrient-containing materials, or as medicaments to treat or prevent infections. In a specific embodiment, the template is based on the D-Pro-L-Pro dipeptides. These β-hairpin peptidomimetics can be manufactured by processes which are based on a mixed solid—and solution phase synthetic strategy.
• US7253146B2
  申请人：——

  公开号：US7253146B2

  公开（公告）日：2007-08-07
• A template for the solid-phase synthesis of conformationally restricted protein loop mimetics
  作者：Fabienne Emery、Christian Bisang、Michel Favre、Luyong Jiang、John A. Robinson

  DOI：10.1039/cc9960002155

  日期：——

  A trifunctional template 1 is synthesized from trans-4-hydroxy-L-proline and L-aspartic acid, immobilized on a solid-support, and used for the solid-phase synthesis of a cyclic conformationally restrained hexapeptide loop mimetic containing the motif Asn-Pro-Asn-Ala (NPNA); this is shown by NMR to populate a stable β-turn conformation in aqueous solution.

  三功能模板1由反式-4-羟基-L-脯氨酸和L-天冬氨酸合成，固定在固体载体上，用于固相合成含Asn-Pro-Asn-Ala（NPNA）模序的环状构象限制性六肽模拟物；NMR显示其在水溶液中形成稳定的β-转角构象。