Synthesis of Formylchromone Derivatives: Inactivators of Protein Tyrosine Phosphatase 1B

In an effort to find potent and specific inhibitors of PTPases, we found that 3-formylchromone (4-oxo-4H-[1]-benzopyran-3-carboxaldehyde, 3-formyl-4-benzopyrone) derivatives inactivate PTPases. Some of them were potent and selective against PTP1B and this result was reported recently. Hereby, we report the synthesis of the formylchromone derivatives. One of the synthetic strategy involves the preparation of appropriately substituted phenol derivatives followed by Friedel-Crafts acylation to obtain 2-acetylphenol derivatives. Alternatively, could be obtained by acetylation prior to the introduction of the substituent R. The core structure was then formed by Vilsmeier-Haack reaction in which 2-acetylphenol moiety in 7 was converted to 3-formylchromone structure in the presence of POCl₃ and DMF. Other routes have been precedented for the construction of 3-formylchromone, but the most convenient was the method via Vilsmeier-Haack reaction