Chemoenzymatic Total Synthesis of Haemophilus ducreyi Lipooligosaccharide Core Octasaccharides Containing Natural and Unnatural Sialic Acids.

Shiwei Luo, Yating Liu, Tianhui Hao, Wenjing Ma, Yawen Luo, Shasha Wang, Zhuojia Xu, Chaoyu Hu, Liuqing Wen, Tiehai Li

Organic letters 2023 Apr 07

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The first total synthesis of Haemophilus ducreyi lipooligosaccharide core octasaccharides containing natural and unnatural sialic acids has been achieved by an efficient chemoenzymatic approach. A highly convergent [3 + 3] coupling strategy was developed to chemically assemble a unique hexasaccharide bearing multiple rare higher-carbon sugars d-glycero-d-manno-heptose (d,d-Hep), l-glycero-d-manno-heptose (l,d-Hep), and 3-deoxy-α-d-manno-oct-2-ulosonic acid (Kdo). Key features include sequential one-pot glycosylations for oligosaccharide assembly and the construction of the challenging α-(1 → 5)-linked Hep-Kdo glycosidic bond by gold-catalyzed glycosylation with a glycosyl ortho-alkynylbenzoate donor. Furthermore, the sequential enzyme-catalyzed regio- and stereoselective introduction of a galactose residue using β-1,4-galactosyltransferase and different sialic acids using a one-pot multienzyme sialylation system was efficiently accomplished to provide the target octasaccharides.

Citation

Shiwei Luo, Yating Liu, Tianhui Hao, Wenjing Ma, Yawen Luo, Shasha Wang, Zhuojia Xu, Chaoyu Hu, Liuqing Wen, Tiehai Li. Chemoenzymatic Total Synthesis of Haemophilus ducreyi Lipooligosaccharide Core Octasaccharides Containing Natural and Unnatural Sialic Acids. Organic letters. 2023 Apr 07;25(13):2312-2317