Synthesis of protected 2-amino-2-deoxy-D-xylothionolactam derivatives and some aspects of their reactivity.
The synthesis of polyfunctionalized delta-lactams as key intermediates of glycomimetics in the 2-acetamido-2-deoxy sugar series is presented. Starting from a chiral gamma-amino vinylic ester synthesized from Garner's 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-delta-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. AM(1) calculations performed on these analogs showed that they adopted a B(2,5) conformation and that the axial epimer was favored in the protected series whereas the equatorial epimer was preferred in the unprotected series.
Devel
Laurent
L
Structure et Fonction de Molécules Bioactives, Université Pierre et Marie Curie, Tour 44-45, 3ème étage, 4 place Jussieu, F-75252 Paris, France.
Hamon
Louis
L
Becker
Hubert
H
Thellend
Annie
A
Vidal-Cros
Anne
A
D007769:Lactams / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D010640:Phenothiazines / Q000737:chemistry*; D014994:Xylose / Q000031:analogs & derivatives / Q000737:chemistry*
C483165:2-amino-2-deoxy-D-xylothionolactam; D007769:Lactams; D010640:Phenothiazines; D014994:Xylose; C009469:thionine