C-glycosyl tyrosines. Synthesis and incorporation into C-glycopeptides

The synthesis of the Fmoc-protected C-glycosyl tyrosines 1 and 2, together with two other related C-glycosyl tyrosines, has been achieved. Key reactio ns involved (i) the reaction of a glycal with an organozinc reagent (carryi ng an aryl iodide function) in the presence of a Lewis acid to establish th e C-glycosyl linkage and (ii) subsequent cross coupling of the aryl iodide to an alanyl zinc reagent (in the presence of a Pd(0) catalyst) to complete the construction of the alpha-amino acid moiety. Using solid-phase peptide synthesis methods, two units of the mannosyl derivative 1 (shown as L-Tyr- [C-Ac-4-alpha-D-Man]) have been incorporated (with four units of glycine) i nto the linear hexapeptide 3 which was then converted to the C-2-symmetric cyclic oligopeptide 4.