C-GLYCOSIDE ANALOGS OF TAMIDO-2-DEOXY-BETA-D-GLUCOPYRANOSYL)-L-ASPARAGINE - SYNTHESIS AND CONFORMATIONAL-ANALYSIS OF A CYCLIC C-GLYCOPEPTIDE

The synthesis of C-glycosidic analogues 15-22 of tamido-2-deoxy-beta-D -glucopyranosyl)-L-asparagine (Asn(N(4)GlcNAc)) possessing a reversed amide bond as an isosteric replacement of the N-glycosidic linkage is presented. The peptide cyclo(-D-Pro-Phe-Ala-CGaa-Phe-Phe-) (CGaa=C-gly cosylated amino acid; 24) was prepared to demonstrate that no]-2-[(9H- fluoren-9-yloxycarbonyl)amino]propanoic acid (22) can be used in solid -phase peptide synthesis. The conformation of 24 was determined by NMR and molecular-dynamics (MD) techniques. Evidence is provided that the CGaa side chain interacts with the peptide backbone. The different C- glycosylated amino acids 15-21 were prepared by coupling 5,7-tri-O-ben zyl-beta-D-deoxy-D-glycero-D-heptonic acid (4) with diamino-acid deriv atives 8-14 in 83-96% yield. The synthesis of 4 was performed from zyl -2-deoxy-beta-D-glucopyranosyl)tributylstannane (2) by treatment with BuLi and CO2 in 83% yield. Similarly, propyl isocyanat yielded the gly coheptonamide 7 in 52% from 2. Compound 2 was obtained from etamido-3, 4,6-tri-O-benzyl-2-deoxy-D-glucopyranose (1) by chlorination and addit ion of tributyltinlithium in 74% yield. A procedure for a multigram-sc ale synthesis of 1 is given.