Progress along a new, straightforward synthetic route towards depsipeptides FK228 and the Spiruchostatins is described.  The key step will involve macrocyclization via pseudo-native chemical ligation (NCL) of an N-terminal D-cysteine (D-Cys) residue and a latent C-terminal thioester functional group—a thioester equivalent—that is stable under the conditions traditionally used for peptide synthesis.  The structural feature that the target molecules share is a macrocycle consisting in part of D-Cys and (E)-3-hydroxy-7-mercapto-4-heptenoate (Hmh) moieties separated by a single D-amino acid residue (alanine, Ala; or valine, Val) and joined at their thiol side chains via an intramolecular disulfide.  As the target compounds are cyclic peptides, each with a single ester linkage, they are envisioned to arise synthetically via straightforward peptide synthesis using their constituent hydroxy- and amino acid subunits.  Furthermore, because a thioester equivalent functional group can be incorporated into a linker for solid-phase synthesis, the solution-phase synthesis illustrated herein is adaptable to the solid phase with no modifications.  Synthesis of analogues of the title depsipeptides with diverse peptide building blocks would therefore be a simple matter of entering different starting materials into SPPS.  Moreover, because the SPPS protocol described here would be quick, new compounds could be generated on demand using commercially available amino acids.