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

Yuan-Ting Cho, Avijit K. Adak, Yung-Yu Su, Ting-Wei ChangChun-Cheng Lin
Advanced Synthesis and Catalysis, 卷.364(20), 頁碼.3573-3588
10/2022

摘要

Enzyme catalysis Ganglioside Glycosphingolipid LLG-5 Sialoside Catalysis Organic Chemistry
LLG-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, Neu5NH 2 (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. (Figure presented.).

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