Surugamides are a group of non-ribosomal peptides isolated from marine-derived Streptomyces . Surugamide A ( 1 ) and its closely related derivatives, surugamides B–E ( 2 – 5 ), are D-amino acid containing cyclic octapeptides with cathepsin B inhibitory activity. The D-isoleucine (Ile), the nonproteinogenic amino acid residue embedded in 1 , is less common in natural peptides because a rare C_β-epimerization is required for its biosynthesis. Taking advantage of the synthetic route of 2 previously established by our group, we synthesized the cyclic octapeptide 1 containing D-Ile by solid phase peptide synthesis. The structure of 1 actually contains D- allo -Ile in place of D-Ile, which was corroborated by chemical syntheses and chromatographic comparisons.