Synthesis and cytotoxic analysis of some disodium 3β,6β-dihydroxysterol disulfates

Disodium 3 beta,6 beta-dihydroxy-5 alpha-cholestane disulfate (1) was synthesized in 4 steps with a high overall yield from cholesterol. First, cholesterol (4a) was converted to cholest-4-en-3,6-dione (5a) via oxidation with pyridinium chlorochromate (PCC) and then 5a was reduced by NaBH4 in the presence of NiCl2 to produce cholest-3 beta,6 beta-diol (6a). The reaction of 6a with the triethylamine-sulfur trioxide complex generated diammonium 3 beta,6 beta-dihydroxy-5 alpha-cholestane disulfate (7a) and the treatment of 7a by cation exchange resin 732 (sodium form)(Na+) yielded the target steroid 1. Disodium 24-ethyl-3 beta,6 beta-dihydroxycholest-22-ene disulfate (2) and disodium 24-ethyl-3 beta,6 beta-dihydroxycholestane disulfate (3) were synthesized using a similar method. The cytotoxicity of these compounds against Sk-Hep-1 (human liver carcinoma cell line), H-292 (human lung carcinoma cell line), PC-3 (human prostate carcinoma cell line) and Hey-1B (human ovarian carcinoma cell line) cells was investigated. Our results indicate that presence of a cholesterol-type side chain at position 17 is necessary for their biological activity. (C) 2009 Elsevier Inc. All rights reserved.