allyl {(2S,6S,8aS)-8a-[(tert-butyl)oxycarbonyl]methyl}perhydro-5,8-dioxo-{[(9H-fluoren-9-yl)methoxycarbonyl]amino}-pyrrolo[1,2-a]pyrazin-6-acetate | 212387-71-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: allyl {(2S,6S,8aS)-8a-[(tert-butyl)oxycarbonyl]methyl}perhydro-5,8-dioxo-{[(9H-fluoren-9-yl)methoxycarbonyl]amino}-pyrrolo[1,2-a]pyrazin-6-acetate
• 英文别名: prop-2-enyl 2-[(3S,7S,8aR)-7-(9H-fluoren-9-ylmethoxycarbonylamino)-8a-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4-dioxo-3,6,7,8-tetrahydro-2H-pyrrolo[1,2-a]pyrazin-3-yl]acetate
• CAS: 212387-71-8
• 化学式: C₃₃H₃₇N₃O₈
• 分子量: 603.672
• InChiKey: GBUSFRXCDHTOKS-MSRXDGMWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  44
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  140
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  allyl {(2S,6S,8aS)-8a-[(tert-butyl)oxycarbonyl]methyl}perhydro-5,8-dioxo-{[(9H-fluoren-9-yl)methoxycarbonyl]amino}-pyrrolo[1,2-a]pyrazin-6-acetate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Synthesis, Conformational Properties, and Immunogenicity of a Cyclic Template-Bound Peptide Mimetic Containing an NPNA Motif from the Circumsporozoite Protein of Plasmodium falciparum

  摘要：

  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.

  DOI：

  10.1021/ja980444j
• 作为产物：
  描述：

  [(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 在 甲基肼 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 allyl {(2S,6S,8aS)-8a-[(tert-butyl)oxycarbonyl]methyl}perhydro-5,8-dioxo-{[(9H-fluoren-9-yl)methoxycarbonyl]amino}-pyrrolo[1,2-a]pyrazin-6-acetate
  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 of template-fixed β-hairpin loop mimetics
  申请人：Robinson John A.

  公开号：US06878804B1

  公开（公告）日：2005-04-12

  Template-fixed β-hairpin loop mimetics comprising a template corresponding to one of the structures (a), (b), (c), (d), (e), (f), (g), (h) and a template-fixed chain of 4 to 20 α-amino acid residues which, if their α-C atom is asymmetric, have L-configuration can be manufactured by a novel process which is based on a mixed solid- and solution phase synthetic strategy. If desired, this process can be modified to give the enantiomers of these template-fixed β-hairpin loop mimetics. These enantiomers are novel compounds, and many of said template-fixed β-hairpin loop mimetics themselves are also novel compounds. The template-fixed β-hairpin loop mimetics and their enantiomers can mimick flat surfaces of proteins and thus be used to probe large surface protein-protein interactions. Accordingly they can serve as lead finding tools for protein targets where it is difficult to find small-molecular-weight lead compounds.

  由模板固定的β-发夹环类似物包括一个与结构（a）、（b）、（c）、（d）、（e）、（f）、（g）、（h）之一相对应的模板和一个由4到20个α-氨基酸残基组成的模板固定链，如果它们的α-C原子是不对称的，则具有L-构型，可以通过一种基于混合固相和溶液相合成策略的新工艺制造。如果需要，该工艺可以修改以给出这些模板固定的β-发夹环类似物的对映体。这些对映体是新化合物，许多所述模板固定的β-发夹环类似物本身也是新化合物。模板固定的β-发夹环类似物及其对映体可以模拟蛋白质的平面表面，因此可以用于探测大面积蛋白质相互作用。因此，它们可以作为寻找小分子靶点的先导化合物的工具，这些靶点很难找到小分子量的先导化合物。