Publications [#234206] of Eric J. Toone
Journal Articles
- Debenham, SD; Cossrow, J; Toone, EJ, "Synthesis of α- and β-carbon-linked serine analogues of the P(k) trisaccharide", Journal of Organic ChemistryDecember,, 1999, 64(25), 9153-9163, American Chemical Society (ACS) [doi].
(last updated on 2024/11/19)Abstract:
The synthesis of glycopeptide ligands for a range of biomedically relevant carbohydrate-binding proteins is a topic of great importance to the glycobiology community. This task is impeded by the inherent instability of glycosyl linkages to serine/threonine, the normal sites of O-glycosylation in proteins. We have previously developed methodology for the preparation of C- glycosylated serines based on catalytic asymmetric hydrogenation of the corresponding enamide esters with the DuPHOS-Rh+ catalysts. Here we report further development of the methodology in the preparation of the C-glycosyl serine analogue of the pk trisaccharide (α-Gal(1→4)β-Gal(1→4)β-Glc-CH2- serine); we require these ligands for our continuing investigations of the binding subunit of the shiga-like toxin. Catalytic asymmetric hydrogenation was used to prepare both α- and β-C-glycosides in the R and S serine series. We report here on the tolerance of the DuPHOS catalysts toward acetate, benzoate, and benzyl hydroxyl protecting groups. Additionally, we have developed an amino acid protecting group strategy compatible with both asymmetric hydrogenation and solid-phase peptide synthesis. In the course of our studies, we have also developed a new methodology for regioselective reductive cleavage of benzylidene protecting groups.