One-Pot Synthesis of Chromone-2-carboxylate Scaffold: An Important Pharmacophore with Diverse Biological Properties

Chromone-2-carboxylate scaffold is growing as an importantpharmacophorein medicinal chemistry with diverse biological properties. We havedeveloped a facile one-pot transformation of 2-fluoroacetophenonedirectly to chromone-2-carboxylate scaffold in a single step via atandem C-C and C-O bond formation. The majority of thepreviously reported medicinal chemistry synthetic protocols primarilyused only one procedure which follows a two-step strategy that needsto start with "2-hydroxyacetophenone". Our methodologynot only serves as an alternative one-pot methodology but also allowschemists to start from different raw materials (2-fluoroacetophenone)other than the traditional ortho-hydroxyacetophenonefor maintaining the regioselectivity in the cyclization step. We furtherdemonstrated the utility of our protocol by successfully extendingthe application to the synthesis of two natural products (Halenicacids A and B), various bis-chromones including drug molecules (DSCG,cromoglicic acid), and potent anti-Alzheimer compound (F-cromolyn).This methodology can serve as a promising alternative tool for findingnew bioactive chromones with diverse modifications due to the opportunityto use new raw materials in the synthesis of chromones.