N-[叔丁氧羰基]-1-(2,4-二硝基苯基)-D-组氨酸 | 103343-26-6

• 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
• 中文名称: N-[叔丁氧羰基]-1-(2,4-二硝基苯基)-D-组氨酸
• 英文名称: Boc-D-(DNP)-His
• 英文别名: Boc-D-(DNP)His-OH；Boc-L-His(DNP)-OH；Boc-D-his(dnp)-OH；(2R)-3-[1-(2,4-dinitrophenyl)imidazol-4-yl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
• CAS: 103343-26-6
• 化学式: C₁₇H₁₉N₅O₈
• 分子量: 421.367
• InChiKey: KPGVUOQMOHGHEW-GFCCVEGCSA-N

物化性质

• 沸点：
  663.2±55.0 °C(Predicted)
• 密度：
  1.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  185
• 氢给体数：
  2
• 氢受体数：
  9

安全信息

• WGK Germany：
  3

反应信息

• 作为反应物：
  描述：

  9H-芴-9-基甲基[(2S,3S)-1-氯-3-甲基-1-氧代-2-戊烷基]氨基甲酸酯 、 Fmoc-D-Pip-Cl 、 N-<(9-fluorenylmethoxy)carbonyl>-L-pipecolic acid chloride 、 N-[叔丁氧羰基]-1-(2,4-二硝基苯基)-D-组氨酸 、 alkaline earth salt of/the/ methylsulfuric acid 在 哌啶 、 肼 作用下， 生成 H-D-β-Nal-Ile-D-Pip-Pip-D-His-Pro-NH-NH2
  参考文献：
  名称：

  Use of N-Fmoc amino acid chlorides and activated 2-(fluorenylmethoxy)-5(4H)-oxazolones in solid-phase peptide synthesis. Efficient syntheses of highly N-alkylated cyclic hexapeptide oxytocin antagonists related to L-365,209

  摘要：

  Fmoc amino acid chlorides have been shown to be useful reagents in the solid-phase synthesis of hexapeptides containing up to four sequential secondary amino acids. The oxytocin antagonist cyclo-(D-Phe-Ile-D-Pip-Pip-D-(N-Me)Phe-Pro) (1) was prepared in 70% overall yield starting from Boc-L-Pro-O-(PAM)-resin. In the synthesis of 1, the high reactivity of Fmoc-L-pipecolic acid chloride used in the di- to tripeptide step averted diketopiperazine formation seen with active ester couplings. The use of Fmoc-amino acid chlorides in the subsequent couplings provided a rapid method for assembly of the linear hexapeptide. The two potent cyclic hexapeptide oxytocin antagonists L-366,682 and L-366,948 were prepared in 45-48% overall yield on a 20 mmol scale using the methodology developed for the synthesis of 1. A particularly difficult coupling was encountered that involved acylation of a sterically hindered N(delta)-Cbz-piperazic acid N-terminus with Fmoc-L-isoleucine. Excess Fmoc-L-isoleucine acid chloride in the presence of tertiary amine base gave only 30% conversion. The efficiency was improved to 76% by utilizing the acid chloride with AgCN in toluene. Further investigation revealed that this combination of reagents produces an activated form of the isoleucine 2-alkoxy-5(4H)-oxazolone derivative.

  DOI：

  10.1021/jo00042a016

文献信息

• Development of a novel class of cyclic hexapeptide oxytocin antagonists based on a natural product
  作者：Peter D. Williams、Mark G. Bock、Roger D. Tung、Victor M. Garsky、Debra S. Perlow、Jill M. Erb、G. F. Lundell、Norman P. Gould、Willie L. Whitter

  DOI：10.1021/jm00099a019

  日期：1992.10

  optimal combination of cyclic amino acid ring sizes at positions 1, 4, and 5 and the role of the N-alkyl substituent at position 6 was elucidated. The lipophilic amino acids at positions 2 and 3 and the unusual amino acid D-dehydropiperazic acid at position 4 were found to be the most critical residues for obtaining good oxytocin receptor affinity. Analogs containing a basic side chain at the less critical

  源自链霉菌的环状六肽催产素拮抗剂的新结构类别，以L-365,209为代表（环-[L-脯氨酰基1-D-苯丙氨酰基2-L-异亮氨酰基3-D-脱氢哌嗪基4-L-脱氢过唑基5-D-（N-甲基）最近报道了苯丙氨酰6]。在本文中，我们通过系统研究通过全合成获得的L-365,209类似物，进一步描述了这一新类的结构活性图谱。阐明了位置1、4和5的环状氨基酸环大小的最佳组合以及位置6的N-烷基取代基的作用。发现在2和3位的亲脂氨基酸和在4位的不寻常氨基酸D-脱氢哌嗪酸是获得良好催产素受体亲和力的最关键的残基。在不太关键的5位和6位上含有基本侧链的类似物保持良好的受体亲和力，并且对于静脉内制剂也具有有用的水溶性水平。通过结合增强效力和溶解性的取代，鉴定了几种在体外具有所需性质组合的类似物（22，环-[L-脯氨酰基-D-色氨酸-L-异亮氨酰基-D-哌啶基-L-pipeco lyl- D-组氨酸]; 25，环-
• <i>p‐</i> Methoxyphenol: A potent and effective scavenger for solid‐phase peptide synthesis
  作者：Jhoan Samacá、Erika Velandia‐Bautista、Luisa Tabares、Luis Escamilla、Magnolia Vanegas、Manuel‐E. Patarroyo

  DOI：10.1002/psc.3251

  日期：2020.6

  t‐Boc/Bzl, solid‐phase peptide synthesis (SPPS)‐protecting groups from amino acids (aa) side chains must be removed from the target peptides during cleavage from the solid support. These reaction steps involve hydrolysis with hydrogen fluoride (HF) in the presence of a nucleophile (scavenger), whose function is to trap the carbocations produced during SN1‐type reactions. Five peptide sequences were synthesised

  在t- Boc / Bzl的最后一步中，在从固相支持物中裂解的过程中，必须从目标肽中去除氨基酸（aa）侧链的固相肽合成（SPPS）保护基。这些反应步骤涉及在亲核试剂（清除剂）存在下用氟化氢（HF）进行水解，其功能是捕获S N 1型反应过程中产生的碳正离子。合成了五个肽序列以评估对甲氧基苯酚作为有效清除剂的有效性。合成后，树脂-肽被分成两个相等的部分，使用两种清除剂进行裂解：常规反应性p-甲酚（在文献中报告为有效的酰基离子消除剂）和对甲氧基苯酚（假设具有与常规使用的清除剂相同的功能）。静电势图（EPM）的详细分析显示，这两个亲核体在净原子电荷，电子密度分布和相似的pKa值方面具有相似性。通过色谱法和质谱结果对合成分子观察到了良好的清除剂功效，这表明对苯甲氧基苯酚可以通过t ‐Boc / Bzl策略在SPPS期间用作有效的清除剂，与使用常规清除剂获得的结果相似。