Nα-(tert-butyloxycarbonyl)-Cα-methyl-D,L-aspartic acid β-cyclohexyl ester | 155567-91-2

• 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: Nα-(tert-butyloxycarbonyl)-Cα-methyl-D,L-aspartic acid β-cyclohexyl ester
• 英文别名: N^α-(tert-butyloxycarbonyl)-C^α-methyl-D,L-aspartic acid β-cyclohexyl ester
• CAS: 155567-91-2
• 化学式: C₁₆H₂₇NO₆
• 分子量: 329.393
• InChiKey: CAYDIPHWAMLXCX-UHFFFAOYSA-N

物化性质

• 沸点：
  491.8±40.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.62
• 重原子数：
  23.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  101.93
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  BOC-甘氨酸 、 Nα-t-BOC-N-α-methyl-Nω-tosyl-L-arginine 、 Nα-(tert-butyloxycarbonyl)-Cα-methyl-D,L-aspartic acid β-cyclohexyl ester 、 3-(N-Boc-氨甲基)苯甲酸 、 alkaline earth salt of/the/ methylsulfuric acid 生成 cyclo(D-Val-N-MeArg-Gly-(S)-C^α-MeAsp-Mamb) 、 cyclo(D-Val-N-MeArg-Gly-(R)-C^α-MeAsp-Mamb)
  参考文献：
  名称：

  Template-Constrained Cyclic Peptides: Design of High-Affinity Ligands for GPIIb/IIIa

  摘要：

  Although peptides adopt a large ensemble of conformations in aqueous solution, they are generally believed to bind to a receptor in a unique conformation. Thus, there is considerable interest in devising methods to restrict the conformational freedom of peptides. One such approach involves tying the amino and carboxy terminal ends of the peptide onto a semirigid template that will lock the intervening peptide backbone into a single conformer or a family of related conformers. This general strategy has been tested using the tripeptide sequence Arg-Gly-Asp (RGD), which binds with low affinity to the platelet glycoprotein IIb/IIIa (GPIIb/IIIa or alpha(IIb)beta(3)) Mimics of RGD are of interest as antithrombotics because of their ability to inhibit the aggregation of platelets. Prior to this study, other workers (Samanen et al. J. Med. Chem. 1991, 34, 3114-3125) prepared a disulfide-containing cyclic pentapeptide that bound to GPIIb/IIIa with an affinity of approximately 0.1 mu M. NMR analysis of the solution conformation of this peptide suggested that replacing the disulfide-containing portion of the cycle with the amino acid m-(aminomethyl)benzoic acid would lead to a more rigid structure. Indeed, introduction of this template into a cyclic ROD-containing peptide resulted in compounds with high affinity for the receptor. Further, systematic inclusion of additional conformational constraints in the form of N-alpha- and C-alpha-alkyl groups led to a peptide with an affinity of approximately 100 pM for binding to the receptor. This peptide also showed good activity in the platelet aggregation assay at oral doses as low as 0.1 mg/kg.

  DOI：

  10.1021/ja00087a007
• 作为产物：
  描述：

  Nα-(tert-butyloxycarbonyl)-Cα-methyl-D,L-aspartic acid α-benzyl ester 在 palladium on activated charcoal 4-二甲氨基吡啶 、 氢气 、 溶剂黄146 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 5.5h， 生成 Nα-(tert-butyloxycarbonyl)-Cα-methyl-D,L-aspartic acid β-cyclohexyl ester
  参考文献：
  名称：

  Template-Constrained Cyclic Peptides: Design of High-Affinity Ligands for GPIIb/IIIa

  摘要：

  Although peptides adopt a large ensemble of conformations in aqueous solution, they are generally believed to bind to a receptor in a unique conformation. Thus, there is considerable interest in devising methods to restrict the conformational freedom of peptides. One such approach involves tying the amino and carboxy terminal ends of the peptide onto a semirigid template that will lock the intervening peptide backbone into a single conformer or a family of related conformers. This general strategy has been tested using the tripeptide sequence Arg-Gly-Asp (RGD), which binds with low affinity to the platelet glycoprotein IIb/IIIa (GPIIb/IIIa or alpha(IIb)beta(3)) Mimics of RGD are of interest as antithrombotics because of their ability to inhibit the aggregation of platelets. Prior to this study, other workers (Samanen et al. J. Med. Chem. 1991, 34, 3114-3125) prepared a disulfide-containing cyclic pentapeptide that bound to GPIIb/IIIa with an affinity of approximately 0.1 mu M. NMR analysis of the solution conformation of this peptide suggested that replacing the disulfide-containing portion of the cycle with the amino acid m-(aminomethyl)benzoic acid would lead to a more rigid structure. Indeed, introduction of this template into a cyclic ROD-containing peptide resulted in compounds with high affinity for the receptor. Further, systematic inclusion of additional conformational constraints in the form of N-alpha- and C-alpha-alkyl groups led to a peptide with an affinity of approximately 100 pM for binding to the receptor. This peptide also showed good activity in the platelet aggregation assay at oral doses as low as 0.1 mg/kg.

  DOI：

  10.1021/ja00087a007