Sialic acids are accessible synthetically by chain extension of 2-acetamido-2deoxy-D-glucose or -D-mannose with oxaloacetate'. However, due to epimerisation at C-2 under alkaline conditions, mixtures of four products are formed, the fractionation of which is sometimes difficult.
The aldehydo-2-acetamido-2-deoxyhexoses2,3 are unstable compounds and cannot be used, without difficulties, for aldol condensations under basic conditions. 2-Acetamido-2-deoxyhexofuranoses are much more stable compounds if HO-3 is not substituted. They readily undergo condensation reactions even under weakly basic conditions and side reactions such as epimerisation or p-elimination are not significant. Hitherto, the glucofuranose derivative 3, required for the synthesis of the manno analogue 5 and of sialic acid derivatives, was accessible only in low yield4. We now describe a simple method for preparing 3 and 5 in high yields.
Under non-aqueous conditions, strong Lewis acids such as FeCl, or BF, *Et,0 act on 2-acetamido-2-deoxy-D-glucopyranose in boiling acetone to yield the oxazoline lc. At lower temperatures, in addition to lc, the furanose derivative 3 is obtained, which decomposes to a mixture of enofuranoses during work-up under strongly alkaline conditions. The results suggest that the reaction is thermodynamically controlled. It is assumed that the action of a strong Lewis acid leads to 3, which is transformed into lc, according to the sequence: 2-acetamido-2-deoxy-oglucose +3 -+-la *lb +lc. Reaction with FeCl, produces crude lc, which can be used either directly or can be purified by chromatography on silica gel. On the other hand, reaction with boron trifluoride yields a less pure product.
The 'H-n.m.r. spectrum of lc shows a characteristic downfield shift (8 6.17) *Dedicated to Professor RezsC) Bogngr in the year of his 75th birthday.