12-Substituted-13,14-dihydroretinols designed for affinity labeling of retinol binding- and processing proteins

All-trans- and 11-cis-retinol derivatives substituted with various electron-withdrawing groups at C12 were designed to be affinity labels for retinol binding and processing proteins. Unlike other non-selective highly reactive affinity labels, these compounds carry a Michael acceptor type substitution at C12 of the polyene chain. Therefore, they are expected to be highly selective towards such proteins that have a nucleophilic residue near the C11 position of their retinol ligand. The synthetic route for these compounds is based on the Emmons–Horner reaction of a C15 aldehyde with an appropriate phosphonate bearing the desired electron-withdrawing group to be incorporated at the C12 position of the retinol skeleton.