Efficient Synthesis of Ratiometric Fluorescent Nucleosides Featuring 3-Hydroxychromone Nucleobases

The synthesis of a novel class of fluorescent nucleosides featuring 2-aryl-3-hydroxychromones (3-HC) as base analogues is described. Nucleoside la bearing the 2-thienyl-3-HC nucleobase was prepared using sequential aryl-aldol condensation/cycloetherification or a Friedel-Crafts glycosylation as key steps. The synthesis of the triazolyl derivative 1b was achieved using a convergent 1,3-dipolar cycloaddition strategy. Fluorescence studies show that 3-HC-thienyl-nucleoside la displays high sensitivity of its dual emission to polarity changes and therefore is highly promising for nucleic acid labelling. (C) 2009 Elsevier Ltd. All rights reserved.