Diastereoselective Alkylation of Schiff Bases for the Synthesis of Lipidic Unnatural Fmoc-Protected alpha-Amino Acids

Peptides with increased lipophilicity can cross cell membranes more easily and have longer half-life times. For these reasons, the synthesis of enantiomerically pure Fmoc-protected lipidic alpha-amino acids is a relevant goal. Schiff bases originating from the reaction between the two enantiomers of 2-hydroxypinan-3-one with Gly-OtBu were alkylated with a series of long alkyl halides. Diastereomeric excesses were determined by reversed-phase HPLC, under conditions carefully chosen for such lipophilic substrates.