Yu Hai, Zheng Zimin, Zhang Libo, Yang Xiaohong, Varki Ajit, Chen Xi
Department of Chemistry, University of California, Davis, California, 95616, USA.
Departments of Medicine and Cellular & Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, California, 92093, USA.
Tetrahedron. 2023 Aug 3;142. doi: 10.1016/j.tet.2023.133522. Epub 2023 Jun 15.
The stable -acetyl analogues of biologically important 9--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--acetylmannosamine (ManNAc6N) as a chemoenzymatic synthon or 6-acetamido-6-deoxy--acetylmannosamine (ManNAc6NAc) as an enzymatic precursor for 9-acetamido-9-deoxy--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--acetylated glycosylsphingosines. Furthermore, glycosylsphingosine acylation reaction conditions were improved to obtain target 9--acetylated gangliosides in a faster reaction with an easier purification process compared to the previous acylation conditions.
包括9NAc-GD3、9NAc-GD2、9NAc-GD1b和9NAc-GT1b在内的具有生物学重要性的9-乙酰化b系列神经节苷脂的稳定乙酰类似物，是通过化学酶法从GM3鞘氨醇合成的。开发并比较了两种化学酶法，一种是以6-叠氮基-6-脱氧-N-乙酰甘露糖胺（ManNAc6N）作为化学酶合成子，另一种是以6-乙酰氨基-6-脱氧-N-乙酰甘露糖胺（ManNAc6NAc）作为9-乙酰氨基-9-脱氧-N-乙酰神经氨酸（Neu5Ac9NAc）的酶促前体，用于合成9NAc-GD3。发现后一种方法更有效，并用于生产所需的9-O-乙酰化糖基鞘氨醇。此外，与之前的酰化条件相比，改进了糖基鞘氨醇酰化反应条件，以更快的反应和更简便的纯化过程获得目标9-O-乙酰化神经节苷脂。
