Synthesis of Complex Carbohydrates.

描述（由申请人提供）：在合成碳水化合物化学领域，糖苷键的立体选择性形成是至关重要的。有效地控制端粒中心的键连通性为合成包括1,2-顺式-2-氨基糖苷在内的复杂碳水化合物开辟了新的途径。这些氨基糖构成了天然低聚糖和糖偶联物中最重要的一类，它们作为凝集素、抗体和酶的细胞表面受体配体起着至关重要的作用。然而，了解1,2-顺式-2-氨基糖的特定功能的进展受到阻碍，因为从天然来源获得足够的定义明确的糖苷是一项艰巨的挑战。在许多情况下，高纯度的1,2-顺-2-氨基糖只能通过化学合成获得，这也为结构变异提供了途径。虽然1,2-顺-2-氨基糖苷的合成已经取得了显著的进展，但现有方法的缺点包括使用过多的活化剂和不可预测/较差的端粒选择性。在这次拨款申请中，我们的目标是

DESCRIPTION (provided by applicant): Within the realm of synthetic carbohydrate chemistry, the stereoselective formation of glycosidic bonds is of paramount importance. Efficient manipulation of bond connectivity at the anomeric center opens up new approaches for the synthesis of complex carbohydrates, including the 1,2-cis-2-amino glycosides. These aminosugars make up one of the most important classes of naturally occurring oligosaccharides and glyco-conjugates, which play a crucial role as cell-surface receptor ligands for lectins, antibodies, and enzymes. However, progress toward understanding the specific functions of 1,2-cis-2-aminosugars has been hampered, due to the formidable challenge of obtaining an adequate supply of well-defined glycosides from natural sources. In many cases, high purity 1,2-cis-2-aminosugars can only be obtained by chemical synthesis, which also provides access to structural variants. Although there have been remarkable advances in the synthesis of 1,2-cis-2-amino glycosides, the disadvantages of current methodologies include the use of excess activating agents and unpredictable/poor anomeric selectivity. In this grant application, our goal is to develop a new and innovative strategy for the effective synthesis of 1,2-cis-2-amino glycosides via transition metal-catalyzed a-selective glycosylation (Specific Aim 1). The method that is currently being developed in our group will be broadly applicable and provide products in high yield and with excellent a-selectivity. The successful completion of the proposed method would have broad impact in the carbohydrate field, where catalytic methods for stereoselective glycosylation are still lacking. This transition-metal catalyzed 1,2-cis-2-amino glycosylation methodology will be applied to the synthesis of bioactive carbohydrate targets, including Campylobacter jejuni N-linked glycan (Specific Aim 2) which can be used to block Campylobacter jejuni adherence to human gastric epithelial cells and biding to mammalian lectins, and heparin oligosaccharides which have potent anticoagulant activity and minimal side effect (Specific Aim 3). 1