Lipophilicity of vinpocetine and related compounds characterized by reversed-phase thin-layer chromatography

A reversed-phase thin-layer chromatographic method was developed and applied to quantitate the lipophilicity of sparingly water-soluble eburnane alkaloids of therapeutic interest. Our method development included calibration, optimization and validation procedures, using also sets of auxiliary compounds. The log P(TLC) values of five relatively hydrophilic eburnanes were verified by stir-flask studies. The alkaloids were found to have lipophilicity values in the 2.9-4.8 log P(TLC) range. Conclusions on structure-lipophilicity relationships were drawn in terms of ring anellation, character and length of side chain, conformational preferences and moiety-solvent interactions, also supported by molecular mechanics studies.