Department of Chemistry, Wayne State University , Detroit, Michigan 48202, United Stated.
J Org Chem. 2013 Dec 20;78(24):12717-25. doi: 10.1021/jo4021979. Epub 2013 Dec 3.
A convergent and efficient strategy was developed for the synthesis of lipomannan (LM), useful for vaccine development. Thioglycosides were employed as glycosyl donors to construct two key pseudotrisaccharide and tetramannose intermediates through preactivation-based glycosylation strategy. These building blocks were then successfully coupled to form the LM core, which was lapidated, phospholipidated, and finally globally deprotected to afford the target molecule. The intermediate LM core involved in this synthesis contained orthogonal protections, which would facilitate its variable modifications for the preparation of other complex LM derivatives and for the synthesis of LM conjugates as LM-based vaccines.
我们开发了一种用于脂甘露聚糖（LM）合成的集中且高效的策略，该方法可用于疫苗开发。我们采用硫糖苷作为糖基供体，通过预活化糖基化策略构建了两个关键的假三糖和四甘露糖中间体。然后，这些砌块成功偶联形成 LM 核心，随后对其进行了硅烷化、磷酰化，最后进行了全保护基脱除，得到目标分子。该合成中涉及的 LM 核心中间体含有正交保护基，这有利于对其进行各种修饰，从而制备其他复杂的 LM 衍生物，并合成作为 LM 疫苗的 LM 缀合物。
