Structural Transformations of N-Acetylneuraminic Acid, XXV: Synthesis of Methyl-2-α-glycosides of 4-Epi-, 7-Epi-, 8-Epi-, and 7,8-Bis-epi-N-acetylneuraminic Acid

Article abstract of DOI:10.1007/BF00811116

The α-methylketoside of N-acetylneuraminic acid methylester (4) is transformed via the deacetylated compound 5 into the 9,8-O-isopropylidenderivative 6 which could be oxidized regioselectively by RuO4 to the corresponding 4-oxo-sialic acid analogue 7.Reduction with the borane-ammonia complex produces a 1:1 mixture of 6 and the desired α-methylketoside of 9,8-O-isopropyliden-4-epi-N-acetyl-neuraminic acid methylester (8).Removing of the isopropylidene group gives the α-methylketoside of 4-epi-N-acetylneuraminic acid methylester (9), which was further transformed to the ammonium salt of 4-epi-N-acetylneuraminic acid α-methylketoside (10).On the other hand compound 5 was turned into the 4,8,9-tri-O-t-butyldimethylsilylderivative 11a from which the corresponding 7-oxo-compound 12 by oxidation with RuO4 derives.The reduction of 12 with BH3-NH3 yielded a 1:1 mixtures of the starting material 11a and the desired 7-epi-derivative 13a which gives either via the purified peracetylated α-methylketoside of 7-epi-N-acetylneuraminic acid methylester (14) or a direct saponification the sodium salt of 7-epi-N-acetylneuraminic acid-α-methylketoside (15).Applying the Koenigs-Knorr procedure to the peracetylated 8-epi-N-acetylneuraminic acid methylester (16) gives rise to the formation of a 1:1 mixture of the corresponding α- and β-methylketosides 17 and 18 besides traces of the corresponding 2,3-dideoxy-2,3-didehydro-sialic acid derivative 19.After chromatographic separation of 17 further saponification leads to the sodium salt of 8-epi-N-acetylneuraminic acid-α-methylketoside (20).In an analogous procedure the sodium salt of 7,8-di-epi-N-acetylneuraminic acid-α-methylketoside (25) was prepared starting from the peracetylated 7,8-di-epi-N-acetylneuraminic acid methylester (21), whereby a mixture of the α- and β-methylketosides 22 and 23 was formed in a ratio 95:5 besides traces of the peracetylated 2,3-dideoxy-2,3-didehydro-sialic acid methylester (24).Keywords.Sialic acid analogoues; Methyl-α-ketosides of sialic aicd analogues.