Date of Award
Master of Science
Alan W. Schwabacher
Peter Geissinger, Alexander E. Arnold
THE SYNTHESIS OF FLUORESCENT 3, 6-DIHYDROXYXANTHONES:
A ROUTE TO SUBSTITUTED FLUORESCEIN
University of Wisconsin-Milwaukee, 2016
Under the Supervision of Professor Alan W Schwabacher
Xanthones belong to the family of compounds of the dibenzo-γ-pyrone framework. Naturally occurring xanthones have been reported to show a wide range of biological and medicinal activities including antifungal,19 antimalarial,20 antimicrobial,21 antiparasitic,22 anticancer,23 and inhibition of HIV activity in cells.24 Xanthones have also been used as a turn on fluorescent probe for metal ions,32 including use as pH indicators, metal ion sensors, in molecular biology, medicinal chemistry and in the construction of other dyes.
Several methods have been developed for the synthesis of this important class of compounds. These methods have several limitations including commercially unavailable or very expensive starting materials, harsh reaction conditions, and multiple steps leading to low overall yields.
In this report I present a simple and efficient method to make 3,6-dihydroxyxanthones in high yields starting with cheap and commercially available starting materials. This transformation involves Friedel-Crafts acylation, Friedel-Crafts alkylation and cyclization of the resulting diarylmethyl cation in a manner mechanistically equivalent to the formation of fluorescein with trifluoroacetic anhydride playing the role of phthalic anhydride.
Fluorination of fluorophores can greatly enhance their photo-stability and improve their spectroscopic properties. 2’, 7’-difluoro derivative of fluorescein has a lower pKa compared to un-substituted fluorescein thereby making it less pH sensitive. Our method offers an easier and efficient 2 steps sequence to make fluorinated xanthones in high yield compared to a 6 step sequence reported in the literature.
Omolabake, Surajudeen, "The Synthesis of Fluorescent 3, 6-dihydroxyxanthones: A Route to Substituted Fluoresceins" (2016). Theses and Dissertations. 1299.