A short method for the synthesis of 4,6-dimethoxy-1-azaaurones

Abstract

Aurones (Benzylidenebenzofuran-3(2H)-one) are naturally occurring compounds, which are isomers of the well known flavones. Like flavones, ring A dioxygenated aurones especially on 4 and 6 positions are frequently found in nature and this substitution pattern is surely responsible for aurones bioactivity. In the present communication, we report the synthesis of ring A-oxygenated 1-azaaurones. These molecules adopt conformations very close to aurones and the presence of the nitrogen can allow derivitization for SAR studies and also making ammonium salts, suitable for the molecule hydrosolubility. The synthesis of 4,6-dimethoxy-1-azaaurones was achieved by condensation of a benzaldehyde derivative with 1-acetyl-4,6-dimethoxy-2,3-dihydro-1H-indole-3-one. The latter was prepared in three steps starting from 3,5-dimethoxyaniline and chloroacetonitrile. If the benzaldehyde derivative is appropriately chosen, the method can allow the preparation of a large number of azaaurones.