Globo A is a neutral Globo-series glycosphingolipid (GSL) that shows natural properties of a cytotoxicity receptor NKp44 binding ligand. The highly complex heptasaccharide glycan structure of Globo A combined with its biological profile provides a unique target for the development of a synthetic method to facilitate its bioactivity studies. Here, a concise chemoenzymatic route to the synthesis of Globo A and its α1,3-galactose-linked congener Globo B is reported. The key to success was the use of a synthetic azido β-Globo H sphingosine (Globo H-βSph) as an acceptor substrate and two glycosyl transferases, an α1,3-N-acetylgalactosaminyltransferase from Helicobacter mustelae (BgtA) and a human blood group B α1,3-galactosyltransferase (h1,3GTB), for stereoselective construction of the terminal α1,3-GalNAc and α1,3-Gal linkages, respectively. The azido-Sph lipid sidechain is further elaborated by reduction and a chemoselective N-acylation to complete the total synthesis of the neutral Globo-series GSLs. In addition, the synthesis of Forssman and para-Forssman antigens were prepared. The strategy may be suitable for accessing other complex GSLs and related lipid-modified GSL derivatives.

Graphical Abstract

中文翻译：

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中性 Globo 系列鞘糖脂 Globo A 和 Globo B 以及 Forssman 和 para-Forssman 抗原的简明化学酶全合成

Globo A 是一种中性 Globo 系列鞘糖脂 (GSL)，显示出细胞毒性受体 NKp44 结合配体的天然特性。Globo A 高度复杂的七糖聚糖结构与其生物学特征相结合，为开发合成方法以促进其生物活性研究提供了独特的目标。在此，报道了合成 Globo A 及其 α1,3-半乳糖连接的同源物 Globo B 的简明化学酶路线。成功的关键是使用合成的叠氮基 β-Globo H 鞘氨醇 (Globo H-βSph) 作为受体底物和两种糖基转移酶，即来自鼬螺杆菌(BgtA) 的 α1,3 -N-乙酰半乳糖胺基转移酶和人类血型B α1,3-半乳糖基转移酶 (h1,3GTB)，分别用于立体选择性构建末端 α1,3-GalNAc 和 α1,3-Gal 连接。通过还原和化学选择性N-酰化进一步精制叠氮基-Sph 脂质侧链，以完成中性 Globo 系列 GSL 的全合成。此外，还制备了福斯曼抗原和副福斯曼抗原的合成物。该策略可能适用于获取其他复杂的 GSL 和相关的脂质修饰的 GSL 衍生物。

图形概要