Synthesis and biological evaluation of 17 beta-alkoxyestra-1,3,5(10)-trienes as potential neuroprotectants against oxidative stress

17 beta -O-Alkyl ethers (methyl, ethyl, propyl, butyl, hexyl, and octyl) of estradiol were obtained from 3-O-benzyl-17 beta -estradiol with sodium hyd ride/alkyl halide, followed by the removal of the O-benzyl protecting group via catalytic transfer hydrogenation. An increase compared to estradiol in the protection of neural (HT-22) cells against oxidative stress due to exp osure of glutamate was furnished by higher (C-3 to C-8) alkyl ethers, while methyl and ethyl ethers decreased the neuroprotective effect significantly . Lipophilic (butyl and octyl) ethers blocking the phenolic hydroxyl (3-OH) of A-ring were inactive.