Cross-metathesis of C-allyl iminosugars with alkenyl oxazolidines as a key step in the synthesis of C-iminoglycosyl alpha-amino acids. A route to iminosugar containing C-glycopeptides

A general access to a novel class of sugar R-amino acids composed of iminofuranose and iminopyranose residues anomerically linked to the glycinyl group through an alkyl chain is described. A set of eight compounds was prepared by the same reaction sequence involving as an initial step the Grubbs Ru-carbene-catalyzed cross-metathesis (CM) of various N-Cbz-protected allyl C-iminoglycosides with N-Boc-vinyl- and N-Boc-allyloxazolidine. The isolated yields of the CM products (mixtures of E- and Z-alkenes) varied in the range 40-70%. Each mixture was elaborated by first reducing the carbon-carbon double bond using in situ generated diimide and then unveiling the N-Boc glycinyl group [CH(BocNH)CO2H] by oxidative cleavage of the oxazolidine ring by the Jones reagent. All amino acids were characterized as their methyl esters. The insertion of a model C-iminoglycosyl-2-aminopentanoic acid into a tripeptide via sequential carboxylic and amino group coupling with L-phenylalanine derivatives was carried out as a demonstration of the potential of these sugar amino acids in designed glycopeptide synthesis.