Imidazole-1-carboxylic acid cyclohexa-2,4-dienylmethyl ester | 359867-74-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: Imidazole-1-carboxylic acid cyclohexa-2,4-dienylmethyl ester
• 英文别名: Cyclohexa-2,4-dien-1-ylmethyl imidazole-1-carboxylate
• CAS: 359867-74-6
• 化学式: C₁₁H₁₂N₂O₂
• 分子量: 204.228
• InChiKey: WMYIHQRMDYUOIK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Imidazole-1-carboxylic acid cyclohexa-2,4-dienylmethyl ester 在 吡啶 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 {(R)-5-[Bis-(4-methoxy-phenyl)-phenyl-methoxy]-3-[(2-cyano-ethoxy)-diisopropylamino-phosphanyloxy]-pentyl}-carbamic acid cyclohexa-2,4-dienylmethyl ester
  参考文献：
  名称：

  COVALENT MODIFICATION AND SURFACE IMMOBILIZATION OF NUCLEIC ACIDS VIA THE DIELS-ALDER BIOCONJUGATION METHOD

  摘要：

  The importance of chemically modified and surface immobilized nucleic acids has inspired the development of a wide variety of complementary techniques for covalent oligonucleotide preparation and immobilization. We are developing technology based on the use of a Diels-Alder reaction for accomplishing the covalent modification of oligonucleotides. Reported herein is preliminary progress toward the establishment of robust reagents for introducing the reactive functionality, as well as studies employing the BIACORE system to demonstrate surface immobilization by the method.

  DOI：

  10.1081/ncn-100002332
• 作为产物：
  描述：

  3-环己烯-1-甲醇 在 咪唑 、 Dowex 50WX₄-50 、 potassium tert-butylate 、 溴 、 甲基三辛基氯化铵 作用下， 以 四氢呋喃 、 甲醇 、 四氯化碳 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.83h， 生成 Imidazole-1-carboxylic acid cyclohexa-2,4-dienylmethyl ester
  参考文献：
  名称：

  Diels−Alder Bioconjugation of Diene-Modified Oligonucleotides

  摘要：

  In an effort to offer complementary technology for covalent biomolecule modification (bioconjugation), we have developed a method that exploits the aqueous acceleration of Diels-Alder reactions for this purpose. Three different diene phosphoramidite reagents have been synthesized that enable diene modification of synthetic oligonucleotides prepared by the phosphoramidite method. Clean and efficient Diels-Alder cycloaddition of these diene oligonucleotides with maleimide dieneophiles was carried out, and the labeled oligonucleotide bioconjugates were characterized by HPLC and electrospray mass spectrometry. Dieneophile stoichiometry, temperature, and pH are all parameters that were shown to influence the efficiency of the process.

  DOI：

  10.1021/jo0100190

文献信息

• Oligonucleotide conjugation to a cell-penetrating (TAT) peptide by Diels–Alder cycloaddition
  作者：Victoria Steven、Duncan Graham

  DOI：10.1039/b807843b

  日期：——

  Modifed oligonucleotides are routinely employed as analytical probes for use in diagnostics, e.g. in the examination of specific RNA sequences for infectious diseases, however, a major limiting factor in oligonucleotide-based diagnostics is poor cellular uptake of naked oligonucleotides. This problem can be overcome by covalent attachment of a so-called ‘cell-penetrating peptide’ to form an oligonucleotide peptide conjugate. Stepwise solid phase synthesis of such a conjugate is difficult and expensive due to the conflicting chemistries of oligonucleotides and peptides. A simple approach to overcome this is post-synthetic conjugation. Diels–Alder cycloaddition is an attractive methodology for oligonucleotide peptide conjugation; the reaction is fast, chemoselective and the reaction rate is greatly enhanced in aqueous media – ideal conditions for biological moieties. An oligodeoxyribonucleotide sequence has been derivatised with a series of dienes at the 5′-terminus, using a series of unique dienyl-modified phosphoramidites, and investigation into the effect of diene type on the efficiency of conjugation, using Diels–Alder cycloaddition with a maleimido-derivatised cell-penetrating (TAT) peptide, has been performed. This led to the observation that the optimal diene for conjugation was cyclohexadiene, allowing conjugation of oligodeoxyribonucleotides to a cell-penetrating peptide by Diels–Alder cycloaddition for the first time.

  经过修饰的寡核苷酸通常被用作诊断分析探针，例如用于检测传染性疾病的特定RNA序列。然而，寡核苷酸诊断的一个主要限制因素是裸寡核苷酸的细胞吸收率低。通过共价连接所谓的 "细胞穿透肽 "来形成寡核苷酸肽共轭物，可以克服这一问题。由于寡核苷酸和肽的化学性质相互冲突，逐步固相合成这种共轭物既困难又昂贵。克服这一问题的简单方法是合成后共轭。DielsâAlder 环加成法是寡核苷酸与肽共轭的一种有吸引力的方法；该反应速度快、化学选择性好，而且在水介质中反应速率大大提高，是生物分子的理想反应条件。利用一系列独特的二烯基修饰的磷酰胺，在寡脱氧核苷酸序列的 5²-末端用一系列二烯进行了衍生，并利用 DielsâAlder 环加成法与马来酰亚胺衍生化的细胞穿透（TAT）肽进行了二烯类型对共轭效率影响的研究。结果发现，最适合共轭的二烯是环己二烯，从而首次实现了通过 DielsâAlder 环加成法将寡脱氧核苷酸与细胞穿透肽共轭。
• US7427678B2
  申请人：——

  公开号：US7427678B2

  公开（公告）日：2008-09-23
• COVALENT MODIFICATION AND SURFACE IMMOBILIZATION OF NUCLEIC ACIDS VIA THE DIELS-ALDER BIOCONJUGATION METHOD
  作者：Gregory M. Husar、Dominick J. Anziano、Michael Leuck、David P. Sebesta

  DOI：10.1081/ncn-100002332

  日期：2001.3.31

  The importance of chemically modified and surface immobilized nucleic acids has inspired the development of a wide variety of complementary techniques for covalent oligonucleotide preparation and immobilization. We are developing technology based on the use of a Diels-Alder reaction for accomplishing the covalent modification of oligonucleotides. Reported herein is preliminary progress toward the establishment of robust reagents for introducing the reactive functionality, as well as studies employing the BIACORE system to demonstrate surface immobilization by the method.
• Diels−Alder Bioconjugation of Diene-Modified Oligonucleotides
  作者：Kenneth W. Hill、Jon Taunton-Rigby、Jeffrey D. Carter、Eric Kropp、Kurt Vagle、Wolfgang Pieken、Danny P. C. McGee、Gregory M. Husar、Michael Leuck、Dominic J. Anziano、David P. Sebesta

  DOI：10.1021/jo0100190

  日期：2001.8.1

  In an effort to offer complementary technology for covalent biomolecule modification (bioconjugation), we have developed a method that exploits the aqueous acceleration of Diels-Alder reactions for this purpose. Three different diene phosphoramidite reagents have been synthesized that enable diene modification of synthetic oligonucleotides prepared by the phosphoramidite method. Clean and efficient Diels-Alder cycloaddition of these diene oligonucleotides with maleimide dieneophiles was carried out, and the labeled oligonucleotide bioconjugates were characterized by HPLC and electrospray mass spectrometry. Dieneophile stoichiometry, temperature, and pH are all parameters that were shown to influence the efficiency of the process.