Synthesis of 1,1-linked galactosyl mannosides carrying a thiazine ring as mimetics of sialyl Lewis X antigen: Investigation of the effect of carboxylgroup orientation on P-selectin inhibition

This paper describes the synthesis of 1,1-linked galactosyl mannosides as s ialyl Lewis X mimetics that contain a spiro-ring to position the carboxylat e group in a well-defined orientation. it was found that compound 4 is more active as a P-selectin inhibitor (IC50 = 19 mu M) than the parent disaccha ride 2, which contains a flexible carboxyl group (IC50 = 193 mu M). This re sult is consistent with that observed in the previous NMR study of sialyl L ewis X bound to P-selectin. The chemistry described here should be useful f or the development of selective inhibitors of E-, P-, and L-selectins.