Here we describe a multistep solid-phase synthetic approach for the addition of amino acid residues to both the C- and N-termini of a phenylstatine core, yielding a library aimed at the development of structure-activity relationships in the S2 and S2' regions of the aspartyl proteases. Optimization of the synthetic strategy was performed on the basis of the in situ analysis of the compounds bound to the solid support through high-resolution magic angle spinning NMR Spectroscopy (HR-MAS NMR).