Synthetic Studies of Oxysterols:methodology for introducing hydroxy groups to ring A of steroids

Abstract

Oxysterols, the oxygenated derivatives of cholesterol, have shown cytotoxic effects to tumour cells. Our research interests were to improve oxysterol cytotoxicities through enhancing hydrophilicity of oxysterol molecules. The aim of this project was to develop methodologies for stereoselectively introducing hydroxy groups to ring A of steroids. For introducing hydroxy groups to the C1 and C4, 5a-hydroxy-6β- acetoxycholest- 2-en-4-one was synthesized from selective oxidation of 5a-Hydroxy-6β-acetoxycholest-2-en with chromium trioxide and 90% aqueous acetic acid. Sa-Hydroxy-6β-acetoxycholest-2-en-l-one was obtained as one of the resulting four compound mixture of the reaction of 5a-hydroxy-6β-acetoxycholest-2-en with chromium trioxide and 3,5- dimethylpyrazole. When 5a,6β-diacetoxycholest-2-en underwent allylic oxidation with chromium trioxide and 3,5-dimethylpyrazole, 5a,6β-diacetoxycholest- 1-en-3-one was obtained as the single product....