Formation of the steroidal 3β-hydroxy-6-oxo-moiety. Synthesis and cytotoxicity of glucolaxogenin

Abstract

An efficient alternative route to the synthesis of the steroidal 3β-hydroxy-6-oxo moiety starting from diosgenin and cholesterol is described. The sequential tosylation, oxidative hydroboration, and selective reduction steps provided the target 3β-hydroxy-6-oxo moiety, yielding laxogenin 1 in 82% and 3β-hydroxycholestan-6-one 8 in 83% overall yield. The cleavage of the S-O bond of 3β-tosylate-6-oxo intermediates was succeeded by means of sodium naphthalenide at -80 °C; when the reduction was explored at room temperature the cleavage of the C-O bond was favored and the corresponding i-steroids were observed. Glucolaxogenin 15 was synthesized in 68% from 1, and its antiproliferative activity was evaluated in cervical cancer cells HeLa, CaSki and ViBo. The effect on peripheral blood lymphocytes was assessed founding that the cell growth was unaffected showing therefore high selectivity.