Total Synthesis of the Proposed Structure of Threoglucin A

We report the first chemical synthesis of the proposed structure of threoglucin A, a fratricidal antibiotic produced by Streptococcus suis . An efficient tandem Mitsunobu cyclization/rearrangement strategy enabled access to all eight diastereomers of the embedded 1,3-oxazinane motif, which were incorporated into the full sequence by solid-phase peptide synthesis. Spectroscopic comparisons with the natural isolate revealed consistent discrepancies, particularly in the modified Thr8-Gln9-Gln10 region. Analysis of model systems and X-ray-validated oxazinanes established characteristic NMR spectroscopic signatures that differ from those reported for the natural products. These findings suggest that the originally proposed structure of threoglucin A warrants revision.