Cu(II) complex of an estradiol derivative with potent anti-inflammatory properties

In the present study, the A-ring of estradiol was converted to an acetylsalicylic structure which was further complexed with Cu(II). The aim was to combine the anti-inflammatory properties of estrogens with those of Cu(II) complexes. Key intermediate of the synthesis was 2-formyl-estradiol (2) which was prepared in quantitative yield through reaction of the phenoxymagnesium bromide of estradiol with formaldehyde in the presence of HMPA. For a successful reaction, an excess of ethylmagnesium bromide was required, and the mechanism is discussed. The target complex 5 exhibited potent anti-inflammatory properties, comparable to those of indomethacin, in the carrageenan-induced rat paw edema. This biological activity was not due either to the steroidal ligand or to the complexed Cu(II) alone.