Design and efficient synthesis of novel GM2 analogues with respect to the elucidation of the function of GM2 activator

摘要

To elucidate the mechanism underlying the hydrolysis of the GalNAc beta 1 -> 4Gal linkage in ganglioside GM2 [GalNAc beta 1 -> 4(NeuAc alpha 2 -> 3)Gal beta 1 -> 4Glc beta 1 -> 1' Cer] by beta-hexosaminidase A (Hex A) with GM2 activator protein, we designed and synthesized two kinds of GM2 linkage analogues-6'-NeuAc-GM2 and alpha-GalNAc-GM2. In this paper, the efficient and systematic synthesis of these GM2 analogues was described. The highlight of our synthesis process is that the key intermediates, newly developed sialyllactose derivatives, were efficiently prepared in sufficient quantities; these derivatives directly served as highly reactive glycosyl acceptors and coupled with GalNTroc donors to furnish the assembly of GM2 tetrasaccharides in large quantities.