SYNTHESIS OF NEW WATER-SOLUBLE CHOLESTEROL DERIVATIVES

Water-soluble cholesterol derivatives for studies investigating the role of cholesterol in mammalian cells under physiological conditions are rare. Therefore, efficient syntheses for new cholesterol derivatives with enhanced water solubility have been developed. Either substitution at C(3)-OH of cholesterol with ethylene glycols or reductive amination at the keto group of pregnenolone yielded steroids with significantly increased water solubility. The solubility of the cholesterol derivatives in water was determined by H-1 NMR spectroscopy in D2O with 2,2-dimethyl-2-silapentane-5-sulfonate (DSS) as reference to be 1 to 6 mg/mL at room temperature. The comparison of resonance signal line width in water and chloroform solution showed little aggregation for compounds 4 and 5, while broader resonance signals indicate micelle formation for compound 9. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications (R) to view the free supplemental file.