脂磷壁酸是革兰氏阳性菌细胞壁的主要组分，对细菌的形态构成和生理机能起着重要的作用。而且脂磷壁酸能够刺激宿主的免疫系统，诱导促炎细胞因子释放，与多种炎症性疾病的发生和发展密切相关。由于其结构的复杂性和微观不均一性，很难从自然界分离获得足够量纯净的、结构完整的脂磷壁酸用于研究。因此，通过有机合成的手段，获得结构确定的脂磷壁酸并研究其免疫活性成为近年来糖化学生物学和免疫学研究的热点和前沿领域。本项目拟发展高效的合成策略制备格氏乳球菌来源的脂磷壁酸系列衍生物：（1）理性设计临时保护基和永久保护基，大量制备正交保护的糖基模块与甘油模块；（2）发展新的酸-碱催化糖苷化策略，高立体选择性地构建目标分子中的1,2-cis半乳糖和葡萄糖苷键。（3）运用“汇聚”合成策略，实现格氏乳球菌来源脂磷壁酸系列衍生物的快速高效组装，并对所合成的脂磷壁酸分子进行免疫刺激活性评价和构效关系研究。

Lipoteichoic acids (LTAs), a major cell wall component of Gram-positive bacteria, play crucial roles in cell shape determination, regulation of cell division, and other fundamental aspects of gram-positive bacterial physiology. Additionally, LTAs have been reported to stimulate pro-inflammatory cytokines release in host innate immune system, and been associated with various inflammatory diseases such as severe sepsis. However, it was difficult to isolate non-contaminated and non-decomposed LTAs from natural sources due to their structural complexity and microheterogeneity. Thus, organic synthesis could provide pure enough and structure defined LTAs for chemical biological and immunological study. .This proposal aims to develop a practical method for the synthesis of LTA derivatives from Lactococcus garvieae. The proposal has two specific aims. Specific Aim 1 is to develop efficient strategy for the synthesis of LTAs from Lactococcus garvieae with defined chain length. This synthetic plan involves orthogonal protection of building blocks: 2-nanphtylmethyl (Nap), tert-butyldiphenylsiyl (TBDPS) and allyl (All) as the temporary protecting groups and benzyl (Bn) as a permanent protecting group. Meanwhile, gold(III) chloride catalyzed acid-base catalysis glycosidation will be used to form the 1,2-cis-D-galacto/glucopyranosidic bonds. Overall, the convergent approach will be applied for the LTA derivatives assembly. Specific Aim 2 is to perform the structural and immunological studies of these synthetic LTAs. The obtained LTA derivatives will be biologically evaluated with respect to their potency to activate cytokines in whole blood cells.