3-(N-Hydroxy-methylamino)-4-methoxy-3-cyclobuten-1,2-dion | 100749-00-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-(N-Hydroxy-methylamino)-4-methoxy-3-cyclobuten-1,2-dion
• 英文别名: 3-methoxy-4-N-methylhydroxylaminocyclobut-3-ene-1,2-dione；3-[Hydroxy(methyl)amino]-4-methoxycyclobut-3-ene-1,2-dione
• CAS: 100749-00-6
• 化学式: C₆H₇NO₄
• 分子量: 157.126
• InChiKey: HYZORUBHCFQWRG-UHFFFAOYSA-N

物化性质

• 熔点：
  177-178 °C (sublm)
• 沸点：
  285.7±50.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(N-Hydroxy-methylamino)-4-methoxy-3-cyclobuten-1,2-dion 在 劳森试剂 、 氢氧化钾 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 12.0h， 生成 (2S,3S)-2-[2-(Hydroxy-methyl-amino)-4-oxo-3-thioxo-cyclobut-1-enylamino]-3-methyl-pentanoic acid methyl ester
  参考文献：
  名称：

  Squaric Acid-Based Peptidic Inhibitors of Matrix Metalloprotease-1

  摘要：

  A series of squaric acid-peptide conjugates were synthesized and evaluated as inhibitors of MMP-1. The cyclobut-3-enedione core was substituted at the 3-position with several functional groups, such as -N(alkyl)OH, -NHOH, and -OH, that are designed to bind to the zinc atom in the active site of the metalloprotease. The 4-position of the cyclobut-3-enedione was derivatized with mono- or dipeptides that are designed to bind in the S1' and S2' subsites of the enzyme, and position the metal chelating group appropriately in the active site for binding to zinc. Positional scanning revealed that -N(Me)OH provided the highest level of inhibition among the chelating groups that were tested, and Leu-Tle-NHMe was the preferred amino acid sequence. A combination of these groups yielded an inhibitor with an IC50 value of 95 mu M. For one inhibitor, conversion of one of the carbonyl groups on the cyclobut-3-enedione core to a thiocarbonyl group resulted in a 18-fold increase in potency, and yielded a compound with an IC50 value of 15 mu M.

  DOI：

  10.1021/jo0517848
• 作为产物：
  描述：

  N-甲基羟胺盐酸盐 、 3,4-二甲氧基-3-环丁烯-1,2-二酮 在 sodium methylate 作用下， 以 甲醇 为溶剂， 以86%的产率得到3-(N-Hydroxy-methylamino)-4-methoxy-3-cyclobuten-1,2-dion
  参考文献：
  名称：

  方酸的羟胺衍生物

  摘要：

  方酸二甲酯 (1) 与等摩尔量的取代羟胺反应得到 3-羟基氨基-4-甲氧基-3-环丁烯-1,2-二酮 2。当二氯方酸与羟胺反应时观察到脱氧反应。

  DOI：

  10.1002/ardp.19853181104

文献信息

• Hydroxylamin-Derivate der Quadratsäure
  作者：Gerwalt Zinner、Johann Grünefeld、Mitarbeit Von Michael Baehr

  DOI：10.1002/ardp.19853181104

  日期：——

  Reaktion von Quadratsäuredimethylester (1) mit äquimolaren Mengen substituierter Hydroxylamine ergibt 3‐Hydroxyamino‐4‐methoxy‐3‐cyclobuten‐1,2‐dione 2. Bei Umsetzung von Quadratsäuredichlorid mit Hydroxylaminen werden Desoxygenierungsreaktionen beobachtet.

  方酸二甲酯 (1) 与等摩尔量的取代羟胺反应得到 3-羟基氨基-4-甲氧基-3-环丁烯-1,2-二酮 2。当二氯方酸与羟胺反应时观察到脱氧反应。
• Squaric Acid <i>N</i>-Hydroxylamides:  Synthesis, Structure, and Properties of Vinylogous Hydroxamic Acid Analogues
  作者：Nathaniel C. Lim、Martha D. Morton、Hilary A. Jenkins、Christian Brückner

  DOI：10.1021/jo035175g

  日期：2003.11.1

  spectroscopic data, chemical reactivity, and iron(III) binding properties. Single-crystal X-ray structure analyses of squaric acid N-hydroxylamide ester 5b and squaric acid N-hydroxylamide amide 6c confirm their connectivity and provide structural evidence supporting the spectroscopically derived conclusions. The squaric acid N-hydroxylamides are potentially useful in the construction of chemosensors for iron(III)

  描述了由方酸二甲酯2a合成方酸N-羟基酰胺酯5和酰胺6。这些衍生物是天然存在的铁（III）螯合剂异羟肟酸的类似物。在比较反应性研究的基础上，提出了一种协调的逆-Cope机理，该机理通过使方酸二甲酯与羟胺反应形成N-羟酰胺酯5。提出了对这些异羟肟酸类似物的铁（III）结合的初步研究，表明铁（III）与水溶液中的酰胺6结合，而酯5没有显示出任何金属离子结合的迹象。这些和相关衍生物的13 C NMR光谱数据（化学位移和自旋晶格弛豫时间测定）描绘了这些分子中主要的共振结构。衍生物的共振结构使它们的光谱数据，化学反应性和铁（III）结合特性合理化。方酸N-羟基酰胺酯5b和方酸N-羟基酰胺酰胺6c的单晶X射线结构分析证实了它们的连通性，并提供了支持光谱学得出结论的结构证据。方酸N-羟基叠氮化物可潜在地用于构建铁（III）的化学传感器。
• ZINNER, G.;GRUENEFELD, J., ARCH. PHARM., 1985, 318, N 11, 977-983
  作者：ZINNER, G.、GRUENEFELD, J.

  DOI：——

  日期：——
• Squaric Acid-Based Peptidic Inhibitors of Matrix Metalloprotease-1
  作者：M. Burak Onaran、Anthony B. Comeau、Christopher T. Seto

  DOI：10.1021/jo0517848

  日期：2005.12.1

  A series of squaric acid-peptide conjugates were synthesized and evaluated as inhibitors of MMP-1. The cyclobut-3-enedione core was substituted at the 3-position with several functional groups, such as -N(alkyl)OH, -NHOH, and -OH, that are designed to bind to the zinc atom in the active site of the metalloprotease. The 4-position of the cyclobut-3-enedione was derivatized with mono- or dipeptides that are designed to bind in the S1' and S2' subsites of the enzyme, and position the metal chelating group appropriately in the active site for binding to zinc. Positional scanning revealed that -N(Me)OH provided the highest level of inhibition among the chelating groups that were tested, and Leu-Tle-NHMe was the preferred amino acid sequence. A combination of these groups yielded an inhibitor with an IC50 value of 95 mu M. For one inhibitor, conversion of one of the carbonyl groups on the cyclobut-3-enedione core to a thiocarbonyl group resulted in a 18-fold increase in potency, and yielded a compound with an IC50 value of 15 mu M.