Abstract
Ganglioside LLG-5 was first isolated from the starfish Linckia laevigata by Higuchi group in 2005 and it shows the activity of stimulating neurogenesis in the rat pheochromocytoma cell line PC-12 in the presence of nerve growth factor. Consequently, LLG-5 was considered as a potential source for the development of carbohydrate-based drugs for curing neurodegenerative diseases. Since the mechanism of action remains unclear due to non-sufficient amount and structurally heterogeneous compounds isolated from the natural resource. We developed an efficient che-moenzymatic strategy to synthesize LLG-5 and its analogues. The synthesis was first performed by using a(2,3)-sialyltransferase Cst-I to couple lactosyl phytosphingosine acceptor with CMP-Neu5Cbz donor. Subsequently, chemical N-acylation with saturated fatty acids yielded GM3 ganglioside derivatives. Finally, the a-2,5-linked Neu5Gc dimers were attached to the amine of C-5 position of GM3 derivatives by amide bond formation. After global removal of all protecting groups, the first total synthesis of the targeted LLG-5 and its analogues were accom-plished.