Aim To synthesize protected aminoalkyl sulfinyl dilactones which were useful as the synthetic intermediates or the Cterminal pharmacophores of potential peptidomimetic proteasome inhibitors. Methods Organic reactions such as reduction, oxidation, olcfmation, and dihydroxylation were used. Results A convenient synthetic procedure to afford a series of aminoalkyl sulfinyl.dilactones was presented, which would be useful in the synthesis of five- or six-member sulfmyl dilactones. Conclusion Four aminoalkyl sulfmyl dilactones connecting different α-amino acids were synthesized.
A series of β-secretase peptidomimetic inhibitors with Leu＊Ala hydroxyethylene dipeptide isostere were synthesized and their β-secretase inhibitory activities were measured. The most potent compound N9 showed an inhibitory rate of 59.66% （10 mg/mL）. Compound N9 might be further modified by means of computational chemical methodology.
Peptidyl epoxyketones were potential antitumor agents due to their 20S proteasome inhibitory activities. Based on their structures and special inhibitory mechanism, a series of compounds were designed by linking the epoxyketone moiety （the Cterminal pharmacophore） and the peptide backbones. To make these compounds, we used a novel method to prepare the terminal α,β-unsaturated ketone, the crucial intermediate, from Weinreb amide with satisfactory yield （62%-65%）.
