Synthesis of glycopeptidomimetics of sialyl Lewis(x) and investigational studies of new processes

Abstract

The solution and solid-phase synthesis of N-linked fucopeptidomimetics of Sialyl Lewisx is described. The syntheses were successful to varying extents. It was determined that t-butyl deprotections are not compatible with the N-glycosidic linkage. This was overcome by the use of benzyl groups. A second series of syntheses were undertaken, involving tartaric acid as the hydroxyacid tail of the molecules. This convergent route was much more rapid, and molecular modelling studies suggested a good congruence with known binding conformations of the natural ligand. C-linked mimetics were also attempted, employing tartaric acid again as the polar tail source. Olefin cross-metathesis was also explored. The work in this area ultimately led to the discovery of a new palladium catalyzed phenyl transfer reaction from antimony. Glycosyl 1,2,3-triazoles were synthesized as glycosylproline analogues. The relative ratios of isomers were determined, and the structure of one analogue proven by Xray crystallography. Deprotection protocols were compatible with the triazolyl moiety. alpha/beta selectivity was observed in coupling protected fucosylamine with amino acids. The scope of the selectivity was examined in related systems. In addition, alpha/beta anomerization as catalyzed by protic acid was examined, and some insights about the mechanism can be gleaned from the results.