N-(4,7-dihydroxy-8-methyl-2-oxo-2H-chromen-3-yl)benzamide | 101601-14-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: N-(4,7-dihydroxy-8-methyl-2-oxo-2H-chromen-3-yl)benzamide
• 英文别名: 3-benzoylamino-4,7-dihydroxy-8-methyl-coumarin；3-Benzoylamino-4,7-dihydroxy-8-methyl-cumarin；N-(4,7-dihydroxy-8-methyl-2-oxochromen-3-yl)benzamide
• CAS: 101601-14-3
• 化学式: C₁₇H₁₃NO₅
• 分子量: 311.294
• InChiKey: WOQFJDWSFXARRE-UHFFFAOYSA-N

物化性质

• 熔点：
  309-310 °C
• 沸点：
  612.6±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)：
  2.3
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(4,7-dihydroxy-8-methyl-2-oxo-2H-chromen-3-yl)benzamide 、 乙酸酐 在 吡啶 作用下， 生成 7-acetoxy-2,6-dimethyl-chromeno[3,4-d]oxazol-4-one
  参考文献：
  名称：

  The Structure of Novobiocin^1,2

  摘要：

  DOI：

  10.1021/ja01571a047
• 作为产物：
  描述：

  N-(4,7-dihydroxy-2-oxo-2H-chromen-3-yl)benzamide 、 S-腺苷-L-蛋氨酸 在 Streptomyces spheroides DSMZ 40292 Strep-tagged NovO C-methyltransferase 作用下， 以 aq. phosphate buffer 、 二甲基亚砜 为溶剂， 生成 N-(4,7-dihydroxy-8-methyl-2-oxo-2H-chromen-3-yl)benzamide
  参考文献：
  名称：

  Molecular characterization of the C-methyltransferase NovO of Streptomyces spheroides, a valuable enzyme for performing Friedel–Crafts alkylation

  摘要：

  The methyltransferase NovO cloned from Streptomyces spheroides could be heterologously produced as soluble and active enzyme in Escherichia coli. Sequencing of the cloned novO gene revealed differences to the GenBank entry AAF67508.1 resulting in a different amino acid at position 223 (Cys instead of Ser). A generated variant containing a Ser residue at this position, however, resulted in poor ability to express soluble and enzymatically active protein. Characterization of NovO revealed a type I methyltransferase that performs its action as a dimer in solution. Functional elements include the conserved S-adenosyl-L-methionine (SAM) binding site (consensus: E/DXXXGXG) as DLCCGSG (residues 45-51). Mutation analyses of the respective amino acids verified their importance for cofactor binding and enzyme activity. In soluble protein fractions of mutants D45N and G49A the calculated kat values decreased from 2.5 x 10(-2) s(-1) of the wild-type protein to 9.7 x 10(-4) s(-1) and 1.2 x 10(-3) s(-1), respectively. A histidine at position 15 was identified as the catalytic base in the methyl transfer reaction. The analysis of purified enzyme preparations showed that the transfer of allyl groups via the SAM analog allyl-SAH occurs with a fourfold increased K-cat of 11 x 10(-3) s(-1) compared to 3.2 x 10(-3) s(-1) for methyl transfer. However, the evolutionary design toward SAM is obvious from the Km value of 0.06 mM compared to 0.22 mM for allyl-SAH. (C) 2012 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.molcatb.2012.03.016

文献信息

• <i>S</i> ‐Adenosyl Methionine Cofactor Modifications Enhance the Biocatalytic Repertoire of Small Molecule <i>C</i> ‐Alkylation
  作者：Iain J. W. McKean、Joanna C. Sadler、Anibal Cuetos、Amina Frese、Luke D. Humphreys、Gideon Grogan、Paul A. Hoskisson、Glenn A. Burley

  DOI：10.1002/anie.201908681

  日期：2019.12.2

  A tandem enzymatic strategy to enhance the scope of C-alkylation of small molecules via the in situ formation of S-adenosyl methionine (SAM) cofactor analogues is described. A solvent-exposed channel present in the SAM-forming enzyme SalL tolerates 5'-chloro-5'-deoxyadenosine (ClDA) analogues modified at the 2-position of the adenine nucleobase. Coupling SalL-catalyzed cofactor production with C-(m)ethyl

  描述了通过原位形成S-腺苷甲硫氨酸（SAM）辅助因子类似物来增强小分子C-烷基化范围的串联酶促策略。SAM形成酶SalL中存在的溶剂暴露通道可耐受在腺嘌呤核苷碱基2位修饰的5'-氯-5'-脱氧腺苷（ClDA）类似物。SalL催化的辅因子生产与甲基转移酶（MTase）催化的C-（间）乙基转移至香豆素底物相结合，相对于使用缺乏核碱基修饰的辅因子获得的C-（间）乙基香豆素具有更高的收率和更大的底物范围。建立影响C-烷基化的分子决定簇为开发用于制备高价值小分子的后期酶促平台提供了基础。
• Biocatalytic Friedel-Crafts Alkylation Using Non-natural Cofactors
  作者：Harald Stecher、Martin Tengg、Bernhard J. Ueberbacher、Peter Remler、Helmut Schwab、Herfried Griengl、Mandana Gruber-Khadjawi

  DOI：10.1002/anie.200905095

  日期：2009.12.7

  A novel biocatalytic protocol for CC bond formation is described and is an equivalent to Friedel–Crafts alkylation. S‐Adenosyl‐L‐methionine (SAM), the major methyl donor for biological methylation catalyzed by methyltransferases (Mtases), can perform alkylations (see scheme). These enzymes can accept non‐natural cofactors and transfer functionalities other than methyl onto aromatic substrates.

  描述了一种新颖的CC键形成的生物催化方案，该方案等同于Friedel-Crafts烷基化。S-腺苷-L-蛋氨酸（SAM）是甲基转移酶（Mtases）催化的生物甲基化的主要甲基供体，可以进行烷基化（请参阅方案）。这些酶可以接受非天然的辅助因子，并且可以将甲基以外的其他功能转移到芳香族底物上。
• A Tandem Enzymatic sp² -C-Methylation Process: Coupling in Situ S-Adenosyl-<scp>l</scp> -Methionine Formation with Methyl Transfer
  作者：Joanna C. Sadler、Luke D. Humphreys、Radka Snajdrova、Glenn A. Burley

  DOI：10.1002/cbic.201700115

  日期：2017.6.1

  A one‐pot, two‐enzyme C‐methylation process is described. Combining SAM production using SalL (Salinospora tropica) with the C‐methyltransferase NovO (Streptomyces spheroides) enables the synthesis of a suite of methylated and ethylated coumarin products, as demonstrated for labelled 13CH3, 13CD3 and CD3 groups from their corresponding SAM analogues.

  描述了一种单锅，两种酶的C-甲基化过程。组合使用SALL（SAM生产Salinospora tropica）与C-甲基NOVO（链霉菌spheroides）使一套甲基化和乙基香豆素产物的合成，这表现为标记13 CH 3，13 CD 3及CD 3组从它们相应的SAM类似物。
• The Structure of Novobiocin^1,2
  作者：J. W. Hinman、E. Louis Caron、Herman Hoeksema

  DOI：10.1021/ja01571a047

  日期：1957.7
• Molecular characterization of the C-methyltransferase NovO of Streptomyces spheroides, a valuable enzyme for performing Friedel–Crafts alkylation
  作者：Martin Tengg、Harald Stecher、Peter Remler、Inge Eiteljörg、Helmut Schwab、Mandana Gruber-Khadjawi

  DOI：10.1016/j.molcatb.2012.03.016

  日期：2012.12

  The methyltransferase NovO cloned from Streptomyces spheroides could be heterologously produced as soluble and active enzyme in Escherichia coli. Sequencing of the cloned novO gene revealed differences to the GenBank entry AAF67508.1 resulting in a different amino acid at position 223 (Cys instead of Ser). A generated variant containing a Ser residue at this position, however, resulted in poor ability to express soluble and enzymatically active protein. Characterization of NovO revealed a type I methyltransferase that performs its action as a dimer in solution. Functional elements include the conserved S-adenosyl-L-methionine (SAM) binding site (consensus: E/DXXXGXG) as DLCCGSG (residues 45-51). Mutation analyses of the respective amino acids verified their importance for cofactor binding and enzyme activity. In soluble protein fractions of mutants D45N and G49A the calculated kat values decreased from 2.5 x 10(-2) s(-1) of the wild-type protein to 9.7 x 10(-4) s(-1) and 1.2 x 10(-3) s(-1), respectively. A histidine at position 15 was identified as the catalytic base in the methyl transfer reaction. The analysis of purified enzyme preparations showed that the transfer of allyl groups via the SAM analog allyl-SAH occurs with a fourfold increased K-cat of 11 x 10(-3) s(-1) compared to 3.2 x 10(-3) s(-1) for methyl transfer. However, the evolutionary design toward SAM is obvious from the Km value of 0.06 mM compared to 0.22 mM for allyl-SAH. (C) 2012 Elsevier B.V. All rights reserved.