Chemoenzymatic Synthesis of N-Acetyl Analogues of 9- O-Acetylated b-Series Gangliosides

Hai Yu; Zimin Zheng; Libo Zhang; Xiaohong Yang; Ajit Varki; Xi Chen

doi:10.1016/j.tet.2023.133522

Chemoenzymatic Synthesis of N-Acetyl Analogues of 9- O-Acetylated b-Series Gangliosides

Tetrahedron. 2023 Aug 3:142:133522. doi: 10.1016/j.tet.2023.133522. Epub 2023 Jun 15.

Authors

Hai Yu¹, Zimin Zheng¹, Libo Zhang¹, Xiaohong Yang¹, Ajit Varki², Xi Chen¹

Affiliations

¹ Department of Chemistry, University of California, Davis, California, 95616, USA.
² Departments of Medicine and Cellular & Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, California, 92093, USA.

PMID: 37981995
PMCID: PMC10653377 (available on 2024-08-03)
DOI: 10.1016/j.tet.2023.133522

Abstract

The stable N-acetyl analogues of biologically important 9-O-acetylated b-series gangliosides including 9NAc-GD3, 9NAc-GD2, 9NAc-GD1b, and 9NAc-GT1b were chemoenzymatically synthesized from a GM3 sphingosine. Two chemoenzymatic methods using either 6-azido-6-deoxy-N-acetylmannosamine (ManNAc6N₃) as a chemoenzymatic synthon or 6-acetamido-6-deoxy-N-acetylmannosamine (ManNAc6NAc) as an enzymatic precursor for 9-acetamido-9-deoxy-N-acetylneuraminic acid (Neu5Ac9NAc) were developed and compared for the synthesis of 9NAc-GD3. The latter method was found to be more efficient and was used to produce the desired 9-N-acetylated glycosylsphingosines. Furthermore, glycosylsphingosine acylation reaction conditions were improved to obtain target 9-N-acetylated gangliosides in a faster reaction with an easier purification process compared to the previous acylation conditions.

Keywords: 9-N-acetyl sialic acid; O-acetyl sialic acid; b-series ganglioside; chemoenzymatic synthesis; glycosphingolipid; one-pot multienzyme.

Abstract

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