Synthesis of betulin derivatives and the determination of their relative lipophilicities using reversed-phase thin-layer chromatography.

A series of superlipophilic or highly lipophilic semisynthetic betulin derivatives was prepared and their relative lipophilicity was measured by reversed-phase thin-layer chromatography (RP-TLC) at different pH values using 1,4-dioxane-acetate buffer mixtures as mobile phases. Cholesterol, 17beta-estradiol and pure betulin were used as the reference compounds. Linear relationships were found between R(M) values and 1,4-dioxane concentrations in the mobile phases. LogP values were also calculated with computer programs ACD/LogP (ChemSketch 11.0, Advanced Chemistry Development Inc.) and ClogP (Daylight Chemical Information Systems Inc.). The empirical and theoretical data were compared, and the R(M0) values correlated well with logP. Two of the synthesized betulin derivatives are reported for the first time. 2009 John Wiley & Sons, Ltd.