6-amino-5-benzyl-3-methylpyrazin-2(1H)-one | 151674-87-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 6-amino-5-benzyl-3-methylpyrazin-2(1H)-one
• 英文别名: 2-Amino-5-benzyl-3-methylpyrazin-2-one；6-amino-5-benzyl-3-methyl-1H-pyrazin-2-one
• CAS: 151674-87-2
• 化学式: C₁₂H₁₃N₃O
• 分子量: 215.255
• InChiKey: QZOAZXZYIDJEGL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  67.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  重氮甲烷 、 6-amino-5-benzyl-3-methylpyrazin-2(1H)-one 以 甲醇 、 乙醚 为溶剂， 反应 2.0h， 以50%的产率得到6-Amino-5-benzyl-1,3-dimethylpyrazin-2-one
  参考文献：
  名称：

  Synthesis and tautomeric equilibrium of 6-amino-5-benzyl-3-methylpyrazin-2-one. An acceptor-donor-donor nucleoside base analog

  摘要：

  6-Aminopyrazin-2-one, when incorporated as pyrimidine base analog into an oligonucleotide, might participate in a nonstandard base pair that retains a Watson-Crick geometry but is joined by a nonstandard hydrogen bonding pattern. Such base pairs can, at least in principle, be recognized independently in duplex nucleic acids. To explore the tautomeric properties that govern hydrogen bonding of this heterocycle, 6-amino-5-benzyl-3-methylpyrazin-2-one was synthesized. The equilibrium constant for the interconversion of the keto and hydroxyl tautomeric forms was estimated by comparing its ultraviolet spectrum with those of N- and 0-methyl derivatives in water, methanol, ethanol, dioxane, and water-dioxane mixtures. A plot of the logarithm of the tautomeric equilibrium constant versus Dimroth's microscopic dielectric constant (ET(30)) was linear. On the basis of an extrapolation of this relationship to the microscopic dielectric of water, 6-amino-5-benzyl-3-methylpyrazin-2-one is expected to favor at equilibrium the keto form over the hydroxyl form by a factor of ca. 2000 under conditions where DNA and RNA polymerases operate. This is substantially better than the tautomeric ratio observed with isoguanosine, where the minor form has been observed to create tautomeric ambiguity with some polymerase systems.

  DOI：

  10.1021/jo00078a038
• 作为产物：
  描述：

  2-Amino-3-benzyl-5-methylpyrazine 1-oxide 在 一水合肼 作用下， 以 乙酸酐 为溶剂， 反应 13.17h， 生成 6-amino-5-benzyl-3-methylpyrazin-2(1H)-one
  参考文献：
  名称：

  Synthesis and tautomeric equilibrium of 6-amino-5-benzyl-3-methylpyrazin-2-one. An acceptor-donor-donor nucleoside base analog

  摘要：

  6-Aminopyrazin-2-one, when incorporated as pyrimidine base analog into an oligonucleotide, might participate in a nonstandard base pair that retains a Watson-Crick geometry but is joined by a nonstandard hydrogen bonding pattern. Such base pairs can, at least in principle, be recognized independently in duplex nucleic acids. To explore the tautomeric properties that govern hydrogen bonding of this heterocycle, 6-amino-5-benzyl-3-methylpyrazin-2-one was synthesized. The equilibrium constant for the interconversion of the keto and hydroxyl tautomeric forms was estimated by comparing its ultraviolet spectrum with those of N- and 0-methyl derivatives in water, methanol, ethanol, dioxane, and water-dioxane mixtures. A plot of the logarithm of the tautomeric equilibrium constant versus Dimroth's microscopic dielectric constant (ET(30)) was linear. On the basis of an extrapolation of this relationship to the microscopic dielectric of water, 6-amino-5-benzyl-3-methylpyrazin-2-one is expected to favor at equilibrium the keto form over the hydroxyl form by a factor of ca. 2000 under conditions where DNA and RNA polymerases operate. This is substantially better than the tautomeric ratio observed with isoguanosine, where the minor form has been observed to create tautomeric ambiguity with some polymerase systems.

  DOI：

  10.1021/jo00078a038

文献信息

• Expanding the Genetic Alphabet: Pyrazine Nucleosides That Support a DonorDonorAcceptor Hydrogen-Bonding Pattern
  作者：Ulrike von Krosigk、Steven A. Benner

  DOI：10.1002/hlca.200490120

  日期：2004.6

  as a pyrimidine-base analog into an oligonucleotide chain, presents a H-bond donordonoracceptor pattern to a complementary DNA or RNA strand. When paired with the corresponding acceptoracceptordonor purine in oligonucleotides, the heterocycle selectively contributes to the stability of the duplex, presumably by forming a base pair of WatsonCrick geometry joined by a nonstandard H-bonding pattern, expanding

  当6-氨基吡嗪-2（1 H）-一作为嘧啶碱基类似物掺入寡核苷酸链时，对互补的DNA或RNA链呈H键供体供体受体形式。当与寡核苷酸中相应的受体-嘌呤嘌呤配对时，杂环可能选择性地形成了双链体的稳定性，大概是通过形成一个由非标准H键连接的WatsonCrick几何碱基对，扩展了遗传字母。这里报道的是通过甘氨酸核糖苷衍生物28的6-氨基吡嗪-2（1 H）-一个核苷的短而高产的β -D选择性合成。关键步骤包括WittigHorner（适当保护的核糖衍生物的反应方案10，19 21），后跟一个迈克尔样环闭合（方案12，30 1A和32 1B）。因此，各种吡嗪核苷（方案13）包括靶标6-氨基吡嗪-2（1 H）-核糖苷1a及其5-甲基衍生物1b，6-氨基-5-甲基吡嗪-2（1 H）-获得一种核糖。
• In vivo conversion of nucleosides in plasmid DNA
  申请人：Benner Steven A

  公开号：US10415088B1

  公开（公告）日：2019-09-17

  Disclosed are processes that use DNA polymerases to extend primers annealed to templates, wherein a standard nucleotide in the template guiding the extension directs the incorporation of a nonstandard nucleotide analog into the product duplex opposite that standard template nucleotide, and processes wherein a nonstandard nucleotide in the template guiding the extension directs the incorporation of a standard nucleotide analog opposite the nonstandard template nucleotide. Conditions, including the pH of the mixture where the primer extension is done and the composition of triphosphate mixtures where the primary extensions done, are disclosed.

  公开了使用 DNA 聚合酶延伸与模板退火的引物的过程，其中模板中的标准核苷酸指导延伸，将非标准核苷酸类似物掺入与该标准模板核苷酸相对的产物双链中；以及模板中的非标准核苷酸指导延伸，将标准核苷酸类似物掺入与该非标准模板核苷酸相对的产物双链中。此外，还公开了一些条件，包括进行引物延伸的混合物的 pH 值和进行初级延伸的三磷酸混合物的成分。
• Polymerase incorporation of non-standard nucleotides
  申请人：Benner Steven A

  公开号：US10865431B1

  公开（公告）日：2020-12-15

  The disclosed invention teaches processes to create a Watson-Crick complementary copy of a preselected oligonucleotide that contain non-standard nucleotides, which form nucleobase pairs fitting the standard Watson-Crick geometry, but here said pairs are joined by hydrogen bonding patterns different from those that join standard A:T and G:C pairs. The invention further relates to polymerases that incorporate those non-standard nucleotide analogs into oligonucleotide products using the corresponding triphosphate derivatives.

  所公开的发明教导了创建预选寡核苷酸的沃森-克里克互补拷贝的过程，该过程包含非标准核苷酸，它们形成符合标准沃森-克里克几何形状的核碱基对，但此处所述核碱基对是通过不同于连接标准 A:T 和 G:C 对的氢键模式连接的。本发明还涉及使用相应的三磷酸衍生物将这些非标准核苷酸类似物结合到寡核苷酸产品中的聚合酶。
• POLYMERASE INCORPORATION OF NON-STANDARD NUCLEOTIDES
  申请人：Benner Steven Albert

  公开号：US20110124053A1

  公开（公告）日：2011-05-26

  The disclosed invention teaches processes to amplify oligonucleotides by contacting templates and primers with DNA polymerases and triphosphates of non-standard nucleotides, which form nucleobase pairs fitting the standard Watson-Crick geometry, but joined by hydrogen bonding patterns different from those that join standard A:T and G:C pairs. Thus, this invention relates to nucleotide analogs and their derivatives that, when incorporated into DNA and RNA, expand the number of replicatable nucleotides beyond the four found in standard DNA and RNA. The invention further relates to polymerases that incorporate those non-standard nucleotide analogs into oligonucleotide products using the corresponding triphosphate derivatives, and more specifically, polymerases and non-standard nucleoside triphosphates that support the polymerase chain reaction (PCR), including PCR where the products contain more than one non-standard nucleotide unit. Examples are provides that show this process using 6-amino-5-nitro-3-(1′-beta-D-2′-deoxyribofuranosyl)-2(1H)-pyridone to implement the non-standard “small” donor-donor-acceptor (pyDDA) hydrogen bonding pattern, and 2-amino-8-(r-beta-D-2′-deoxyribofuranosyl)-imidazo[1,2-α]-1,3,5-triazin-4(8H)-one to implement the “large” acceptor-acceptor-donor (puADD) pattern.
• US6140496A
  申请人：——

  公开号：US6140496A

  公开（公告）日：2000-10-31