N-tert-Butyloxycarbonyl-L-isoleucine 2-bromoethyl ester | 287178-39-6

• 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
• 英文名称: N-tert-Butyloxycarbonyl-L-isoleucine 2-bromoethyl ester
• 英文别名: 2-bromoethyl N-(tert-butoxycarbonyl)-L-isoleucinate；N-Boc-L-isoleucine；2-bromoethyl (2S,3S)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoate
• CAS: 287178-39-6
• 化学式: C₁₃H₂₄BrNO₄
• 分子量: 338.242
• InChiKey: SESCANUASHMXTF-UWVGGRQHSA-N

物化性质

• 沸点：
  403.6±25.0 °C(Predicted)
• 密度：
  1.239±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-tert-Butyloxycarbonyl-L-isoleucine 2-bromoethyl ester 在 butyrylcholine esterase 、 氢溴酸 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二异丙基碳二亚胺 作用下， 以 phosphate buffer 、 二氯甲烷 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 168.5h， 生成 N-Benzyloxycarbonyl-L-seryl(O-2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)-L-isoleucine
  参考文献：
  名称：

  Enzymatic Protecting Group Techniques for Glyco- and Phosphopeptide Chemistry: Synthesis of a Glycophosphopeptide from Human Serum Response Factor

  摘要：

  The covalent modification of proteins by phosphorylation and by glycosylation with GlcNAc residues are important regulatory processes which mediate biological signal transduction. For the study of such biological phenomena in molecular detail characteristic peptides which embody both types of modification may serve as efficient tools. However, their synthesis is complicated by their pronounced acid and base lability as well as their multifunctionality. For this purpose the enzyme labile choline ester was developed. The choline ester can be removed selectively and in high yields from various GlcNAc-glycopeptides and phosphopeptides at pH 6.5 and 37 degrees C. The conditions under which the enzymatic deprotections proceed are so mild that no undesirable side reactions are observed (i.e., no cleavage or anomerization of the glycosidic bonds and no beta-elimination of the phosphate or the carbohydrate occur). The specificity of the biocatalyst guarantees that neither the peptide bonds nor the other protecting groups present are being attacked. When this enzymatic protecting group technique was combined with the enzyme-labile 4-(phenylacetoxy)benzyloxycarbonyl (PhAcOZ) urethane protecting group a complex glycophosphopeptide could be built up. The glycopeptide is equipped with a biotin label by which it can be traced in biological systems. This peptide represents a characteristic partial structure of a glycosylated and phosphorylated sequence from the transactivation domain of serum response factor (SRF), a widely occuring human transcription factor.

  DOI：

  10.1002/(sici)1521-3765(20000502)6:9<1564::aid-chem1564>3.3.co;2-h
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 2-bromoethyl (2S,3S)-2-amino-3-methylpentanoate 在 三乙胺 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 24.5h， 以95%的产率得到N-tert-Butyloxycarbonyl-L-isoleucine 2-bromoethyl ester
  参考文献：
  名称：

  Enzymatic Protecting Group Techniques for Glyco- and Phosphopeptide Chemistry: Synthesis of a Glycophosphopeptide from Human Serum Response Factor

  摘要：

  The covalent modification of proteins by phosphorylation and by glycosylation with GlcNAc residues are important regulatory processes which mediate biological signal transduction. For the study of such biological phenomena in molecular detail characteristic peptides which embody both types of modification may serve as efficient tools. However, their synthesis is complicated by their pronounced acid and base lability as well as their multifunctionality. For this purpose the enzyme labile choline ester was developed. The choline ester can be removed selectively and in high yields from various GlcNAc-glycopeptides and phosphopeptides at pH 6.5 and 37 degrees C. The conditions under which the enzymatic deprotections proceed are so mild that no undesirable side reactions are observed (i.e., no cleavage or anomerization of the glycosidic bonds and no beta-elimination of the phosphate or the carbohydrate occur). The specificity of the biocatalyst guarantees that neither the peptide bonds nor the other protecting groups present are being attacked. When this enzymatic protecting group technique was combined with the enzyme-labile 4-(phenylacetoxy)benzyloxycarbonyl (PhAcOZ) urethane protecting group a complex glycophosphopeptide could be built up. The glycopeptide is equipped with a biotin label by which it can be traced in biological systems. This peptide represents a characteristic partial structure of a glycosylated and phosphorylated sequence from the transactivation domain of serum response factor (SRF), a widely occuring human transcription factor.

  DOI：

  10.1002/(sici)1521-3765(20000502)6:9<1564::aid-chem1564>3.3.co;2-h

文献信息

• Design and synthesis of novel bis(l-amino acid) ester prodrugs of 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) with improved anti-HBV activity
  作者：Xiaozhong Fu、Saihong Jiang、Chuan Li、Jian Xin、Yushe Yang、Ruyun Ji

  DOI：10.1016/j.bmcl.2006.10.021

  日期：2007.1

  A series of novel bis(L-amino acid) ester prodrugs of 9-[2-(phosphonomethoxy)ethyl] adenine (PMEA) was synthesized and their anti-HBV activity was evaluated in HepG 2 2.2.15 cells. Compounds 11, 12, 21, 22, 26, and 27 demonstrated more potent anti-HBV activity and higher selective index (SI) than adefovir dipivoxil, which was used as a positive control. Compound 11, which was found to be the most potent

  合成了一系列新型的9- [2-（膦酰基甲氧基）乙基]腺嘌呤（PMEA）双（L-氨基酸）酯前药，并在HepG 2 2.2.15细胞中评估了它们的抗HBV活性。与用作阳性对照的阿德福韦酯相比，化合物11、12、21、22、26和27表现出更强的抗HBV活性和更高的选择性指数（SI）。被发现是最有效的化合物11，其效力是阿德福韦酯的5倍，EC50值为0.095 microM，CC50值为6636 microM。化合物11的SI值（> 69,000）分别比阿德福韦酯和拉米夫定高60倍和24倍。体外稳定性研究表明，化合物11比阿德福韦酯更稳定，t1 / 2为270分钟。
• Design, Synthesis, and Anti-HBV Activity of New Bis(<scp>l</scp>-amino acid) Ester Tenofovir Prodrugs
  作者：Apeng Wang、Shuo Wu、Zeyu Tao、Xiaoning Li、Kai Lv、Chao Ma、Yuhuan Li、Linhu Li、Mingliang Liu

  DOI：10.1021/acsmedchemlett.9b00184

  日期：2019.6.13

  A series of bis(l-amino acid) ester prodrugs of tenofovir (TFV) were designed and synthesized as new anti-HBV agents in this work. Four compounds 11, 12a, 12d, and 13b displayed better anti-HBV activity (IC50: 0.71–4.22 μM) than the parent drug TFV. The most active compound 11 (IC50: 0.71 μM), a bis(l-valine) ester prodrug of TFV, was found to have obviously greater AUC0–∞,Cmax, and F% than tenofovir

  设计并合成了一系列替诺福韦（TFV）的双（1-氨基酸）酯前药，作为这项工作中的新型抗HBV药物。四种化合物11、12a，12d和13b表现出比母体药物TFV更好的抗HBV活性（IC 50：0.71-4.22μM）。发现活性最高的化合物11（IC 50：0.71μM）是TFV的双（1-缬氨酸）酯前药，其富马酸替诺福韦酯（TDF）的AUC 0–∞，C max和F％明显更高，体内有力 在鸭HBV（DHBV）模型和HBV DNA流体动力学小鼠模型中疗效不亚于TDF，并且它可以作为进一步发现抗HBV药物的有前途的先导化合物。
• Synthesis, anti-HBV activity and renal cell toxicity evaluation of mixed phosphonate prodrugs of adefovir
  作者：Xiao-Zhong Fu、Yu Ou、Jian-Ying Pei、Ying Liu、Jing Li、Wen Zhou、Yan-Yu Lan、Ai-Min Wang、Yong-Lin Wang

  DOI：10.1016/j.ejmech.2012.01.013

  日期：2012.3

  A series of phosphonate ester prodrugs of adefovir incorporating L-amino (thio)acid and non-steroidal anti-inflammatory drug (NSAID) moieties were synthesized and their anti-HBV activity and renal cell toxicity were evaluated in HepG2 2.2.15 and HK-2 cells respectively. Bioactivity evaluation results revealed that this kind of adefovir prodrug have lower renal cell toxicity than adefovir dipivoxil. Compounds 8a and 8b, incorporating the NSAID ketoprofen and the L-amino acid (Val or Ile) structural fragments, exhibited more potent anti-HBV activity than adefovir dipivoxil with IC50 = 0.51 and 0.73 mu M, SI = 1697.64 and 881.92 respectively. In vitro stability studies showed that the synthesized prodrugs have higher chemical and plasma stability than the positive control adefovir dipivoxil. (C) 2012 Elsevier Masson SAS. All rights reserved.
• AN IMPROVED SYNTHETIC PROCESS FOR YF-6, A PROMISING ANTI-HBV DRUG CANDIDATE
  作者：Sai Hong Jiang、Peng Lu、Xiao Zhong Fu、Yu She Yang、Ru Yun Ji

  DOI：10.1080/00304940809458108

  日期：2008.10
• Design, synthesis and evaluation of novel scutellarin and scutellarein-N,N-bis-substituted carbamate-l-amino acid derivatives as potential multifunctional therapeutics for Alzheimer’s disease
  作者：Dirong Wu、Jiao Chen、Keke Luo、Hui Li、Ting Liu、Li Li、Zeqin Dai、Yongjun Li、Yonglong Zhao、Xiaozhong Fu

  DOI：10.1016/j.bioorg.2022.105760

  日期：2022.5