AURONE: DERIVATIZATION, REACTION METHODOLOGY DEVELOPMENT, AND ITS UTILIZATION AS A FLUOROPHORE FOR DEVELOPING A FLUOROGENIC PROBE FOR SENSING HYDROGEN SULFIDE

Abstract

Aurones, a sub-class of the flavonoids with proven therapeutic importance, also exist in variously glycosylated forms. Although a large number of glycosylated aurone derivatives have been isolated from plant sources, no syntheses have been reported yet. Inspired from this gap, here we report the first synthesis of peracetylated glycosyl derivatives of synthetic aurones. The direct O-glycosylation was achieved by reacting 6-hydroxy aurones with 2, 3, 4, 6-tetra-O-acetyl-α-D glucopyranosyl bromide in the presence of a phase transfer catalyst tetrabutylammonium bromide (TBAB). The successful synthesis of aurone glycosides (33 examples) in 60-92% yield will benefit the synthesis of combinatorial libraries of glycosylated aurones for their biological study and comparison with non-glycosylated aurones. Similarly, in an attempt to prepare azido-substituted aurones via a copper-catalyzed azidation, the reaction failed to afford the desired product but instead resulted in an unusual triazole formation reaction. Further efforts noted that copper was not required for this reaction but simply thermal treatment with sodium azide in a polar aprotic solvent. A wide range of substitution patterns was tolerated in this reaction to afford the interesting salicyl-substituted triazoles in modest to excellent yield. While the mechanism is not yet clear, a simple elimination/cyclization pathway seems unlikely given the failure of the reaction on the corresponding thioaurones, which feature an even better thiol leaving group. Regardless, the potential utility of these easily accessible, multifunctional compounds should engender further interest and applications. Besides derivatizing aurone scaffolds for combinatorial library synthesis and developing a reaction protocol for the synthesis of a unique and unexplored salicyl-substituted triazoles scaffold, we utilized the aurone scaffold to develop a fluorescent probe for hydrogen sulfide detection in biological as well as environmental situations. While many methods are currently available, the most sensitive and biologically applicable ones are fluorescent-based. In general, these fluorescent probes are based upon large, high-molecular-weight, and well-characterized fluorescent scaffolds that are synthetically demanding to prepare and difficult to tune and modify. We have developed a new system based upon a synthetically simple aurone scaffold that features good sensitivity, selectivity for hydrogen sulfide, and has potential for application in a variety of contexts.