Synthesis of 1,1-Linked Galactosyl Mannosides Carrying a Thiazine Ring as Mimetics of Sialyl Lewis X Antigen: Investigation of the Effect of Carboxyl Group Orientation on P-Selectin Inhibition

Article abstract of DOI:10.1021/jo991556b

This paper describes the synthesis of 1,1-linked galactosyl mannosides as sialyl Lewis X mimetics that contain a spiro-ring to position the carboxylate group in a well-defined orientation. It was found that compound 4 is more active as a P-selectin inhibitor (IC₅₀ = 19 μM) than the parent disaccharide 2, which contains a flexible carboxyl group (IC₅₀ = 193 μM). This result is consistent with that observed in the previous NMR study of sialyl Lewis X bound to P-selectin. The chemistry described here should be useful for the development of selective inhibitors of E-, P-, and L-selectins.