Efficient Synthetic Approach to Fluorescent Oxazole-4-carboxylate Derivatives

Abstract

In our attempt to synthesize a halogenated analog of green fluorescent protein (GFP) chromophore, we discovered a simple and efficient synthetic strategy to the derivatives of oxazole-4-carboxylic acid substituted at positions 2 and 5. The method allows for introduction of different aryl substituents at the position 5, aryl or alkyl substituents at position 2 of oxazole, and gives access not only to free carboxyl at position 4, but also to a range of its amide derivatives. The advantages of the synthetic strategy presented are availability of precursors, good yields, and avoiding palladium coupling and metalation procedures. The synthesized compounds fluoresce in visible region with quantum yields up to 0.82. We believe that 5-aryl-4-carboxyoxazole is a promising core for creation of new fluorescent dyes.

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GRAPHICAL ABSTRACT

Keywords:

• Azlactones
• fluorescence
• green fluorescent protein
• heterocycles
• oxazoles

ACKNOWLEDGMENTS

We gratefully acknowledge grants by the Molecular and Cell Biology program of the Russian Academy of Sciences, the Ministry of Education and Science of the Russian Federation (16.740.11.0367 and 16.512.11.2139), and the Russian Foundation for Basic Research (11-04-01293-a). B. M. S. is supported by the stipendial program of the President of Russia Federation.

Notes

^a In the presence of 10 mM NaOH.