Synthesis of protected 2-amino-2-deoxy-d-xylothionolactam derivatives and some aspects of their reactivity

The synthesis of polyfunctionalized δ-lactams as key intermediates of glycomimetics in the 2-acetamido-2-deoxy sugar series is presented. Starting from a chiral γ-amino vinylic ester synthesized from Garnerʹs aldehyde and after regioselective reduction, 1-azido-3-(N-tert-butyloxycarbonyl-2,2-dimethyloxazolidin-4-yl)-2-propene was obtained. Next, a cis-dihydroxylation reaction provided the protected d-xylitol and l-arabinitol azides. A simple protection-deprotection sequence, followed by an oxidation and a reductive cyclization, led to protected 2-amino-δ-lactams bearing a tert-butyloxycarbonyl group on the amine functionality. To explore the reactivity of such compounds, activation of the lactam into the corresponding thionolactam was performed. The resulting 2-amino-d-xylothionolactam derivative, a versatile intermediate, allowed access to a first generation of protected 2-amino-d-xylosamidoxime derivatives which are of interest as precursors of N-acetylhexosaminidase and N-acetylglucosaminyltransferase inhibitors. In this series of compounds, epimerization at C-2 was observed. AM1 calculations performed on these analogs showed that they adopted a B2,5 conformation and that the axial epimer was favored in the protected series whereas the equatorial epimer was preferred in the unprotected series.