Loading...
Efficient and Scalable Synthesis of 4-Carboxy-Pennsylvania Green Methyl Ester: A Hydrophobic Building Block for Fluorescent Molecular Probes
Woydziak, Zachary R. Fu, Liqiang Peterson, Blake R.
Woydziak, Zachary R.
Fu, Liqiang
Peterson, Blake R.
Citations
Altmetric:
Abstract
Fluorinated fluorophores are valuable tools for studies of biological systems. However, amine-reactive single-isomer derivatives of these compounds are often very expensive. To provide an inexpensive alternative, we report a practical synthesis of 4-carboxy-Pennsylvania Green methyl ester. Derivatives of this hydrophobic fluorinated fluorophore, a hybrid of the dyes Oregon Green and Tokyo Green, are often cell permeable, enabling labeling of intracellular targets and components. Moreover, the low pKa of Pennsylvania Green (4.8) confers bright fluorescence in acidic cellular compartments such as endosomes, enhancing its utility for chemical biology investigations. To improve access to the key intermediate 2,7-difluoro-3,6-dihydroxyxanthen-9-one, we subjected bis-(2,4,5-trifluorophenyl)methanone to iterative nucleophilic aromatic substitution by hydroxide on scales of > 40 g. This intermediate was used to prepare over 15 grams of pure 4-carboxy-Pennsylvania Green methyl ester in 28% overall yield without requiring chromatography. This compound can be converted into the amine reactive N-hydroxysuccinimidyl ester in essentially quantitative yield for the synthesis of a wide variety of fluorescent molecular probes.
Description
Date
2015-01-01
Journal Title
Journal ISSN
Volume Title
Publisher
Thieme Publishing
Collections
Research Projects
Organizational Units
Journal Issue
Keywords
Fluorophore, Bioorganic chemistry, Chemical biology, Molecular probes, Fluorine, Conjugation
Citation
Peterson, Blake, Zachary Woydziak, and Liqiang Fu. "Efficient and Scalable Synthesis of 4-Carboxy-Pennsylvania Green Methyl Ester: A Hydrophobic Building Block for Fluorescent Molecular Probes." Synthesis 46.02 (2013): 158-64.