2-methyl-4-oxo-4H-chromene-5,7-diyl diacetate | 56147-47-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 2-methyl-4-oxo-4H-chromene-5,7-diyl diacetate
• 英文别名: 5,7-diacetoxy-2-methyl-chromen-4-one；5,7-Diacetoxy-2-methyl-chromen-4-on；(5-Acetyloxy-2-methyl-4-oxochromen-7-yl) acetate
• CAS: 56147-47-8
• 化学式: C₁₄H₁₂O₆
• 分子量: 276.246
• InChiKey: NGWCDEHNPJCDII-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  78.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-methyl-4-oxo-4H-chromene-5,7-diyl diacetate 在 N-溴代丁二酰亚胺(NBS) 、 水 、 sodium carbonate 、 zinc(II) chloride 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 12.0h， 生成 6-Bromo-8-((3-ethyl-5,7-dihydroxy-8-methyl-4-oxochroman-6-yl)-methyl)-5,7-dihydroxy-2-methyl-4H-chromen-4-one
  参考文献：
  名称：

  Derivatives of Natural Product Agrimophol as Disruptors of Intrabacterial pH Homeostasis in Mycobacterium tuberculosis

  摘要：

  This article reports the rational medicinal chemistry of a natural product, agrimophol (1), as a new disruptor of intrabacterial pH (pH(IB)) homeostasis in Mycobacterium tuberculosis (Mtb). Through the systematic investigation of the structure-activity relationship of 1, scaffold-hopping of the diphenylmethane scaffold, pharmacophore displacement strategies, and studies of the structure-metabolism relationship, a new derivative 5a was achieved. Compound 5a showed 100-fold increased potency in the ability to reduce pH(IB) to pH 6.0 and similarly improved mycobactericidal activity compared with 1 against both Mycobacterium bovis-BCG and Mtb. Compound 5a possessed improved metabolic stability in human liver microsomes and hepatocytes, lower cytotoxicity, higher selectivity index, and similar pK(a) value to natural 1. This study introduces a novel scaffold to an old drug, resulting in improved mycobactericidal activity through decreasing pH(IB), and may contribute to the critical search for new agents to overcome drug resistance and persistence in the treatment of tuberculosis.

  DOI：

  10.1021/acsinfecdis.8b00325
• 作为产物：
  描述：

  2,4,6-三羟基苯乙酮一水合物 在 吡啶 、 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 6.0h， 生成 2-methyl-4-oxo-4H-chromene-5,7-diyl diacetate
  参考文献：
  名称：

  椴木叶中色酮和苯并氧杂的合成及抗真菌活性。

  摘要：

  该研究报告了具有生物活性的 oxepinochromones 12- O-乙酰基白质素 ( 8 )（角异构体）和 12- O-乙酰基ptaeroxylinol ( 9 )（线性异构体）的首次全合成。测定了这些化合物及其衍生物对白色念珠菌和新型隐球菌的抗真菌活性。大多数化合物在两种真菌之间具有良好的选择性，并显示出中等至良好的活性。12- O-乙酰基花青素 ( 8 ) 对白色念珠菌的活性最高，MIC 值为 9.9 μM，而 12- O-乙酰基丁二烯酚 ( 9 )，其存在于Ptaeroxylonobliquum对新型隐球菌的活性最高，MIC 值为 4.9 μM。

  DOI：

  10.1021/acs.jnatprod.0c00587

文献信息

• TMSI-Promoted Vinylogous Michael Addition of Siloxyfuran to 2-Substituted Chromones: A General Approach for the Total Synthesis of Chromanone Lactone Natural Products
  作者：Jie Liu、Zhanchao Li、Pei Tong、Zhixiang Xie、Yuan Zhang、Ying Li

  DOI：10.1021/jo502571r

  日期：2015.2.6

  A concise and facile synthetic protocol for the construction of the 2-gamma-lactone chromanone skeleton has been achieved through a TMSI-promoted diastereoselective vinylogous Michael addition of siloxyfuran to 2-substituted chromones. The applicability of this method is demonstrated through the rapid access to the total syntheses of (+/-)-microdiplodiasone, (+/-)-lachnone C, and (+/-)-gonytolides C and G.
• Synthese de trihydroxyphenacylidenetriphenylphosphoranes une nouvelle voie d'acces aux dihydroxyflavones (chrysine, acacetine…)
  作者：Yves Le Floc'h、Martine Lefeuvre

  DOI：10.1016/s0040-4039(00)85249-1

  日期：1986.1
• Jochum; v. Kostanecki, Chemische Berichte, 1904, vol. 37, p. 2101
  作者：Jochum、v. Kostanecki

  DOI：——

  日期：——
• FLOCH V. LE; LEFEUVRE M., TETRAHEDRON LETT., 27,(1986) N 45, 5503-5504
  作者：FLOCH V. LE、 LEFEUVRE M.

  DOI：——

  日期：——
• Derivatives of Natural Product Agrimophol as Disruptors of Intrabacterial pH Homeostasis in <i>Mycobacterium tuberculosis</i>
  作者：Jie Wu、Ran Mu、Mingna Sun、Nan Zhao、Miaomiao Pan、Hongshuang Li、Yi Dong、Zhaogang Sun、Jie Bai、Minwan Hu、Carl F. Nathan、Babak Javid、Gang Liu

  DOI：10.1021/acsinfecdis.8b00325

  日期：2019.7.12

  This article reports the rational medicinal chemistry of a natural product, agrimophol (1), as a new disruptor of intrabacterial pH (pH(IB)) homeostasis in Mycobacterium tuberculosis (Mtb). Through the systematic investigation of the structure-activity relationship of 1, scaffold-hopping of the diphenylmethane scaffold, pharmacophore displacement strategies, and studies of the structure-metabolism relationship, a new derivative 5a was achieved. Compound 5a showed 100-fold increased potency in the ability to reduce pH(IB) to pH 6.0 and similarly improved mycobactericidal activity compared with 1 against both Mycobacterium bovis-BCG and Mtb. Compound 5a possessed improved metabolic stability in human liver microsomes and hepatocytes, lower cytotoxicity, higher selectivity index, and similar pK(a) value to natural 1. This study introduces a novel scaffold to an old drug, resulting in improved mycobactericidal activity through decreasing pH(IB), and may contribute to the critical search for new agents to overcome drug resistance and persistence in the treatment of tuberculosis.