3-甲基-1-(2,4,6-三羟基-3-甲基苯基)-1-丁酮 | 49583-27-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 3-甲基-1-(2,4,6-三羟基-3-甲基苯基)-1-丁酮
• 英文名称: 1-[2,4,6-trihydroxy-3-methylphenyl]isopentan-1-one
• 英文别名: 3-isovaleroyl-2,4,6-trihydroxytoluene；3-methyl-1-(2,4,6-trihydroxy-3-methyl-phenyl)-butan-1-one；3-Methyl-1-(2,4,6-trihydroxy-3-methyl-phenyl)-butan-1-on；1-Butanone, 3-methyl-1-(2,4,6-trihydroxy-3-methylphenyl)-；3-methyl-1-(2,4,6-trihydroxy-3-methylphenyl)butan-1-one
• CAS: 49583-27-9
• 化学式: C₁₂H₁₆O₄
• 分子量: 224.257
• InChiKey: AQGJJVVGIDQMHX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  77.8
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-甲基-1-(2,4,6-三羟基-3-甲基苯基)-1-丁酮 在 四氯化钛 、 四乙基对甲苯磺酸铵 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 硝基甲烷 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 euglobal G1
  参考文献：
  名称：

  Electrochemical synthesis of euglobal-G1, -G2, -G3, -G4, -T1 and -IIc

  摘要：

  通过电化学方法合成了六种天然尤格洛布林。关键步骤是在聚四氟乙烯纤维涂层电极表面，现场生成的喹诺甲烷与萜类化合物进行环加成反应，以2,3-二氯-5,6-二氰基对苯二酚（DDQH2）作为氧化还原介质，得到天然产物。在该反应体系中，通过对甲酚衍生物的选择性氧化，高效地完成了不稳定喹诺甲烷的仿生生成和环加成反应。

  DOI：

  10.1039/a802306i
• 作为产物：
  描述：

  间苯三酚 在 盐酸 、 aluminum (III) chloride 、 sodium cyanoborohydride 、 三氯氧磷 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 、 1,2-二氯乙烷 为溶剂， 生成 3-甲基-1-(2,4,6-三羟基-3-甲基苯基)-1-丁酮
  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

文献信息

• Synthesis of euglobal-G3 and -G4
  作者：Kazuhiro Chiba、Takaaki Arakawa、Masahiro Tada

  DOI：10.1039/cc9960001763

  日期：——

  The first, concise synthesis of euglobals is accomplished by biomimetic cycloaddition of β-pinene and quinone methides generated by oxidation of grandinol.

  首个简洁的尤戈全球合成是通过生物仿制的环加成反应，使用由格兰迪烯氧化生成的β-松油烯和醌烯醇。
• Inagaki et al., Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1956, vol. 76, p. 1258
  作者：Inagaki et al.

  DOI：——

  日期：——
• Five phloroglucinol-monoterpene adducts from Eucalyptus grandis
  作者：Kazuhiro Umehara、Inder Pal Singh、Hideo Etoh、Midori Takasaki、Takao Konoshima

  DOI：10.1016/s0031-9422(98)00289-1

  日期：1998.11

  Five new euglobals possessing the phlorogiucinol-monoterpene structure, euglobals G8-G12, together with a known euglobal-IIc were isolated from the hexane fraction of the methanol extract of the leaves of Eucalyptus grandis. Euglobal-G8 is an adduct of formyl-isovaleroyl-phloroglucinol and gamma-terpinene whereas -G9, -G10 and -G11 have the same phloroglucinol moiety fused with alpha-terpinene, while Euglobal-G12 has terpinolene fused with the same phloroglucinol moiety. The structures of these compounds were elucidated on the basis of spectral evidences. Biomimetic synthesis of euglobals suggests that these compounds are derived biogenetically by the Diels-Alder type cycloaddition of the corresponding terpenes with an ortho-quinone methide generated from grandinol. (C) 1998 Elsevier Science Ltd. All rights reserved.
• Electrochemical synthesis of euglobal-G1, -G2, -G3, -G4, -T1 and -IIc
  作者：Kazuhiro Chiba、Takaaki Arakawa、Masahiro Tada

  DOI：10.1039/a802306i

  日期：——

  Six natural euglobals were synthesized by electrochemical methods. In a key step, cycloaddition between in situ generated quinomethanes and terpenes was performed on the surface of PTFE-fibre coated electrode to give natural products using 2,3-dichloro-5,6-dicyano-p-hydroquinone (DDQH2) as a redox mediator. In this reaction system, biomimetic generation and cycloaddition of the unstable quinomethanes were efficiently completed by the selective oxidation of cresol derivatives.

  通过电化学方法合成了六种天然尤格洛布林。关键步骤是在聚四氟乙烯纤维涂层电极表面，现场生成的喹诺甲烷与萜类化合物进行环加成反应，以2,3-二氯-5,6-二氰基对苯二酚（DDQH2）作为氧化还原介质，得到天然产物。在该反应体系中，通过对甲酚衍生物的选择性氧化，高效地完成了不稳定喹诺甲烷的仿生生成和环加成反应。
• 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.