Chemoenzymatic Total Synthesis of the Neuritogenic Echinoderm Ganglioside LLG‐5 and Related Analogues

Abstract

AbstractLLG‐5 1 is a Neu5Gc8Me‐containing echinoderm ganglioside (EG) isolated from starfish Linckia laevigata. It showed neuritogenic activity toward the rat adrenal pheochromocytoma cell line PC‐12. The first chemoenzymatic total synthesis of the trisialoganglioside LLG‐5 1 has been accomplished by utilizing a convergent [2+3] coupling between a Neu5Gc8Meα(2→5)Neu5Gc‐linked disialoside and a C5‐amino GM3 ceramide, Neu5NH2(2→3)Galβ(1→4)Glcβ‐Cer. A photoactivatable lactosyl phytosphingosine bearing a sulphonate moiety was developed to permit aqueous buffer solubility of the hydrophobic glycolipid acceptor for enzymatic α(2,3) sialylation. In addition, the synthetic route is flexible, allowing non‐natural LLG‐5 analogues in native lengths with or without modification at C8 of the terminal Neu5Gc and/or N‐acyl component, further expanding the diversity of LLG‐5 structures that could be achieved. The developed synthetic strategy may enable access to other EGs.magnified image