D-甘露糖立体选择性beta-糖苷化新方法及其应用

Beta-D-mannose and mannuronic acid are common building blocks in a wide range of naturally occurring products. Owing to disfavorable kinetic anomeric effect and steric hinderance of axial substituent at 2 position,the synthesis of beta-D-mannospyranoside is one of the most charllenging tasks in carbohydrate chemistry. To develop highly efficient and easily-handled methodologies and strategies for the synthesis of beta-D-mannospyranosides, this project aims to investigate Lewis acid-catalyzed beta-glycosylations of mannosyl- and mannuronyl- ortho-alkynyl phosphites as novel glycosyl donors. Based on the mothods, common core pentasaccharide of N-glycoproteins, sulfated trisaccaride arising from polysaccharide of bacterial strain Pseudoalteromonas HYD 721, and 24 pieces of well-defined oligomannuronates and their sulfated as well as selectively sulfated derivatives, which are resulted from polymannuronate(PM) and JG3 possessing unique structures and exhibiting antivirus and anticancer bioactivities will be also accomplished in this projects.Because it is very difficult for degradation to obtain the selectively sulfated oligomannuronate, therefore,their successful synthesis followed by bioactivity tests will favor both better understanding of structure-activity relationships of antivirus and anticancer of sulfated oligomannuronates and the determination of minimmum active fragment of PM and JG3, which may accelerate the development and applications of oligomannuronats.

Beta-D-甘露糖和甘露糖醛酸是多种活性天然产物中常见的构造单元，但由于不利的异头位效应和2位直立键取代基的空间位阻，它们的合成是糖化学中最具挑战性的目标之一。为发展高效合成beta-D-甘露糖苷的简便方法与策略，该项目将研究路易酸催化的新型甘露糖和甘露糖醛酸邻炔基膦酸酯给体的beta-糖苷化反应, 并应用这些方法完成N-糖蛋白核心五糖、细菌菌株Pseudoal teromonas HYD 721胞外多糖中硫酸化三糖片段和24个结构明确的甘露糖醛酸二糖、四糖和六糖及其硫酸化和选择性硫酸化产物。系列甘露糖醛酸寡糖及其硫酸化产物来源于具有独特结构和抗病毒、抗癌活性的甘露糖醛酸多糖(PM)和JG3，但通过降解很难获得选择性的硫酸化寡糖，因此，它们的成功合成和活性筛选，有助于更好地理解硫酸化甘露糖醛酸寡糖生物活性的构效关系和PM以及JG3的最小活性寡糖片段的确定，从而加快甘露糖醛酸寡糖的开发利用

该项目围绕着甘露糖和甘露糖醛酸-糖苷键的新型方法的建立和应用。通过四年的执行， 我们建立了甘露糖和甘露糖醛酸邻炔基苯甲酸酯给体的-糖苷化反应的方法，并将它们应用于acremannolipid A、褐藻胶-(1 → 4)-甘露糖醛酸四糖片段的合成以及kakelokelose 三糖、六糖、九糖以及硫酸化片段的合成；另外我们发展了一种利用金催化的薯蓣皂苷元邻炔基苯甲酸酯醚化反应，合成了多个新型的薯蓣皂苷元糖复合物，为基于甾体皂苷药物的研发提供新的合成技术和可供筛选的底物；再有，通过项目实施，我们也建立了金催化的邻炔基磷酸酯给体和联烯酸酯糖基给体新型糖苷化反应，并完成了11-deoxyheloside A 、7个呋甾皂苷、硫酸化甘露糖苷和紫檀素及其类似物的全合成。