3-dichloro-5,5-difluoro-7-methoxy-10-(4-(2-methoxy-2-oxoethoxy)-2,6-dimethylphenyl)-5H-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-4-ium-5-uide | 1309582-36-2

• 英文名称: 3-dichloro-5,5-difluoro-7-methoxy-10-(4-(2-methoxy-2-oxoethoxy)-2,6-dimethylphenyl)-5H-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-4-ium-5-uide
• CAS: 1309582-36-2
• 化学式: C₂₁H₂₀BClF₂N₂O₄
• 分子量: 448.662
• InChiKey: FHIVRDUWZFKJFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  None
• 重原子数：
  None
• 可旋转键数：
  None
• 环数：
  None
• sp3杂化的碳原子比例：
  None
• 拓扑面积：
  None
• 氢给体数：
  None
• 氢受体数：
  None

反应信息

• 作为反应物：
  描述：

  3-dichloro-5,5-difluoro-7-methoxy-10-(4-(2-methoxy-2-oxoethoxy)-2,6-dimethylphenyl)-5H-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-4-ium-5-uide 在 LiOH 作用下， 以 四氢呋喃 、 甲醇 、 乙腈 为溶剂， 生成 3-(bis(2-((2-(ethylthio)ethyl)thio)ethyl)amino)-10-(4-(2-carboxmethoxy)-2,6-dimethylphenyl)-5,5-difluoro-7-methoxy-5H-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-4-ium-5-uide
  参考文献：
  名称：

  A Targetable Fluorescent Sensor Reveals That Copper-Deficient SCO1 and SCO2 Patient Cells Prioritize Mitochondrial Copper Homeostasis

  摘要：

  We present the design, synthesis, spectroscopy, and biological applications of Mitochondrial Coppersensor-1 (Mito-CS1), a new type of targetable fluorescent sensor for imaging exchangeable mitochondrial copper pools in living cells. Mito-CS1 is a bifunctional reporter that combines a Cu+-responsive fluorescent platform with a mitochondrial-targeting triphenylphosphonium moiety for localizing the probe to this organelle. Molecular imaging with Mito-CS1 establishes that this new chemical tool can detect changes in labile mitochondrial Cu+ in a model HEK 293T cell line as well as in human fibroblasts. Moreover, we utilized Mito-CS1 in a combined imaging and biochemical study in fibroblasts derived from patients with mutations in the two synthesis of cytochrome c oxidase 1 and 2 proteins (SCO1 and SCO2), each of which is required for assembly and metalation of functionally active cytochrome c oxidase (COX). Interestingly, we observe that although defects in these mitochondrial metallochaperones lead to a global copper deficiency at the whole cell level, total copper and exchangeable mitochondrial Cu+ pools in SCO1 and SCO2 patient fibroblasts are largely unaltered relative to wild-type controls. Our findings reveal that the cell maintains copper homeostasis in mitochondria even in situations of copper deficiency and mitochondrial metallochaperone malfunction, illustrating the importance of regulating copper stores in this energy-producing organelle.

  DOI：

  10.1021/ja2004158
• 作为产物：
  描述：

  3,7-dichloro-5,5-difluoro-10-(4-(2-methoxy-2-oxoethoxy)-2,6-dimethylphenyl)-5H-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-4-ium-5-uide 、 sodium methylate 以 四氢呋喃 、 甲醇 为溶剂， 以84%的产率得到3-dichloro-5,5-difluoro-7-methoxy-10-(4-(2-methoxy-2-oxoethoxy)-2,6-dimethylphenyl)-5H-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-4-ium-5-uide
  参考文献：
  名称：

  A Targetable Fluorescent Sensor Reveals That Copper-Deficient SCO1 and SCO2 Patient Cells Prioritize Mitochondrial Copper Homeostasis

  摘要：

  We present the design, synthesis, spectroscopy, and biological applications of Mitochondrial Coppersensor-1 (Mito-CS1), a new type of targetable fluorescent sensor for imaging exchangeable mitochondrial copper pools in living cells. Mito-CS1 is a bifunctional reporter that combines a Cu+-responsive fluorescent platform with a mitochondrial-targeting triphenylphosphonium moiety for localizing the probe to this organelle. Molecular imaging with Mito-CS1 establishes that this new chemical tool can detect changes in labile mitochondrial Cu+ in a model HEK 293T cell line as well as in human fibroblasts. Moreover, we utilized Mito-CS1 in a combined imaging and biochemical study in fibroblasts derived from patients with mutations in the two synthesis of cytochrome c oxidase 1 and 2 proteins (SCO1 and SCO2), each of which is required for assembly and metalation of functionally active cytochrome c oxidase (COX). Interestingly, we observe that although defects in these mitochondrial metallochaperones lead to a global copper deficiency at the whole cell level, total copper and exchangeable mitochondrial Cu+ pools in SCO1 and SCO2 patient fibroblasts are largely unaltered relative to wild-type controls. Our findings reveal that the cell maintains copper homeostasis in mitochondria even in situations of copper deficiency and mitochondrial metallochaperone malfunction, illustrating the importance of regulating copper stores in this energy-producing organelle.

  DOI：

  10.1021/ja2004158