Synthesis Of Steroid-derived Compounds With β-lactone Substructure

Proteasome catalyze the degradation of protein and controls the process of intracellular protein degradation. As a target of cancer treatment, people paid more and more attention to it recently, and the proteasome inhibitors became the focus of anti-cancer drug research. The presence of four-membered ring lactone structure in the natural compounds can form covalent adduct with theβ5-subunit of 20S proteasome, which inhibits the activity of 20S proteasome and enhances the chemical sensitivity of cancer cells, and promotes the apoptosis of cancer cell. The structure ofβ-lactone is the pharmacophore of these compounds.We used cholesterol, diosgenin and DHEA as starting materials to react with acetic anhydride, ethyl chloride, etc., respectively, obtaining the corresponding ester products: cholesteryl acetate, diosgenin acetate, DHEA acetate, etc. Oxidation and cyclyzation of the esters led to steroid-derived compounds withβ-lactone substructure. Some of these compounds had not been reported. The structures of the lactones were analyzed and identified by IR, 1H-NMR.With the presence ofβ-lactone substructure, these compounds are expected to inhibit the activity of 20S proteasome. The anti-cancer activities of these compounds will be checked later.