Synthesis of lacto- and neolacto-series ganglioside analogs containing N-glycolylneuraminic acid: Probes for investigation of specific receptor structures recognized by influenza A viruses

Sialic acids are essential components of host-cell surface receptors for infection of influenza virus. To investigate the specific receptor structures recognized by various influenza A viruses, a series of lacto- and neolacto-series ganglioside analogs containing N-glycolylneuraminic acid (Neu5Gc) have been synthesized. The pentasaccharide structures of Neu5Gc-alpha-(2-->3)/(2-->6)-lactotetraose (IV(3(6))Neu5GcLcOse) and Neu5Gc-alpha-(2-->3)/(2-->6)-neolactotetraose (IV(3(6))Neu5GcnLcOse) were constructed by glycosylation of the suitably protected trisaccharide acceptors (2A and 2B) with the Neu5Gc-alpha-(2-->3)/(2-->6)-Gal trichloroacetimidate donors (1 and 21), respectively. Transformation of the 2-(trimethylsilyl)ethyl group at the reducing end in 4, 11, 23, and 30 into the trichloroacetimidate group gave a series of Neu5Gc-alpha-(2-->3)/(2 -->6)-lacto- and neolactotetraose donors (7, 13, 26, and 33), which were coupled with 2-(tetradecyl)hexadecanol (8), to give the corresponding glycolipids (9, 14, 27, and 34). Finally, the complete removal of the O-acyl groups and saponification of the methyl ester group gave the desired ganglioside analogs (10, 15, 28, and 35).