An expeditious route to N-glycolylneuraminic acid based on enzyme-catalyzed reaction

• Published in: Tetrahedron Vol. 53; no. 7; pp. 2387 - 2400
• Main Authors: Kuboki, Atsuhito, Okazaki, Hanako, Sugai, Takeshi, Ohta, Hiromichi
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 17.02.1997; Elsevier
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; ACYLNEURAMINATE-PYRUVATE LYASE; NEURAMINIC ACID; ORGANIC-SYNTHESIS; CONTAINING GANGLIOSIDES; HANGANUTZIU-DEICHER ANTIGEN; CMP-SIALIC ACID; ESCHERICHIA-COLI; CARBOHYDRATE SYNTHESIS; INFLUENZA-VIRUS; ACETYLNEURAMINIC ACID
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/S0040-4020(96)01189-1

A new preparative way of N-glycolylneuraminic acid (NeuGc), one of the important family of sialic acids, from N-acetylglucosamine (GlcNAc) via N-acetylmannosamine (ManNAc) was established based on the combination of chemical and enzymatic reactions. In a kinetic study of the key enzymatic reaction for this process, aldolase-catalyzed synthesis of sialic acid, an inhibitory effect of gluco-isomer on the enzymatic reaction was quantitatively clarified, and the importance of isomerically pure substrate with manno-configuration for aldolase-catalyzed reaction was suggested. A newly developed method, selective degradation of GlcNAc contaminating in the substrate by use of Rhodococcus rhodochrous IFO 15564 provided pure ManNAc to avoid such inhibitory effect of the gluco-isomer for aldolase. Starting from pure ManNAc, via mannosamine hydrochloride, acetoxyacetyl chloride was applied for introducing a protected form of glycolyl group to give N-acetylglycolylmannosamine. For the removal of acetyl protective group, a lipase from Aspergillus niger was effectively used under a mild and neutral condition to afford N-glycolylmannosamine (ManNGc), the substrate of aldolase. NeuGc was prepared in 25% yield and 7 steps from GlcNAc. N-Glycolylneuraminic acid (NeuGc) was prepared in 25% yield and 7 steps from N-acetylglucosamine (GlcNAc) via N-acetylmannosamine (ManNAc) based on the combination of chemical and enzymatic reactions.