Highly Efficient α-Sialylation by Virtue of Fixed Dipole Effects of N-Phthalyl Group: Application to Continuous Flow Synthesis of α(2-3)-and α(2-6)-Neu5Ac-Gal Motifs by Microreactor

Highly alpha-selective sialylation of sialic acid N-phenyltrifluoroacetimidate with various galactose and lactose acceptors has been achieved by introducing the C-5 N-phthalyl group on the donor. The "fixed dipole effect" of the N-phthalyl group was proposed to explain the high reactivity and a-selectivity. The microfluidic system was applied to the present alpha-sialylation, which is amenable to large-scale synthesis. The N-phthalyl group was removed by treatment with methylhydrazine acetate, for which protocol can be readily applied to the synthesis of a variety of sialic acid-containing oligosaccharides. [GRAPHICS]