Regioselective aectylations of sialic acid α‐ketosides

Various partially acetylated sialic acid α-ketosides were obtained without expensive protecting group techniques by using trimethyl orthoacetate or dimethylacetamide dimethyl acetal as acetylating agents or by performing a partial Zemplen de-O-acetylation. Using trimethyl orthoacetate as acetylating agents we synthesized 9-O-acetylated, 8-O-acetylated, and 8,9-di-O-acetylated sialic acid α-ketoside benzyl ester derivatives. The acetylation with dimethylacetamide dimethyl acetal yielded 9-O-acetylated, 8-O-acetylated, 4, 9-di-O-acetylated, 8,9-di-O-acetylated, and 4,8,9-tri-O-acetylated sialic acid α-ketoside benzyl ester derivatives. The partial Zemplen de-O-acetylation permitted the synthesis of 7,8,9-tri-O-acetylated sialic acid α-ketoside benzyl ester derivatives. After catalytic hydrogenation the 8-O-acetylated derivatives 2e and 3d were not stable and were completely converted into the 9-O-acetylated sialic acid α-thioketoside 2k. The N-acetyl-8,9-di-O-acetylneuraminic acid α-aminophenylthioketoside 21 showed a migration of the acetyl group from position 8 to position 7 in polar solvents, yielding a mixture of the 8,9-di-O- and the 7, 9-di-O-acetylated derivatives 21 and 2m in a molar ratio of approximately 1:1. The 7, 9-di-O-acetylated derivative 2m could be separated and was completely stable in methanol. Using the isopropylidene protecting group we could also prepare the 4-O-acetylated sialic acid α-thioketoside 2o. Treatment of the 9-O-acetylated derivative 2k with fluorescein isothiocyanate gave the fluorescent derivative 5.