ORGN 840 |
| Progress along a new, straightforward synthetic route toward 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, called a thioester equivalent, that is stable under the conditions traditionally used for peptide synthesis. 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 route illustrated herein is adaptable to the solid phase with no modifications. Synthesis of analogs of the title depsipeptides would therefore be a simple matter of entering different starting materials into SPPS. New compounds could thus be generated on demand using commercially available amino acids. |
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Combinatorial, Parallel and Process Chemistry, Heterocycles, Aromatics, New Reactions and Methodology
8:00 PM-10:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster
Sci-Mix
Division of Organic Chemistry |