Synthesis of Complex Carbohydrates.

复杂碳水化合物的合成。

基本信息

批准号：
8449104
负责人：
Hien M Nguyen
金额：
$ 27.24万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-04-01 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8449104
关键词：
Adherence Advanced Development Adverse effects Affinity Alcohols Amino Sugars Antibiotic Resistance Antibiotics Antibodies Anticoagulants Antithrombins Applications Grants Area Asparagine Binding Biochemical Process Blood Clot Blood coagulation Calorimetry Campylobacter jejuni Carbohydrate Chemistry Carbohydrates Cardiovascular system Cell Surface Receptors Cells Cessation of life Collaborations Complex Complication Coupling Development Diagnosis Diarrhea Disadvantaged Discipline Enzymes Epithelial Cells Evaluation Fluoroquinolones Glucosamine Glycoconjugates Glycosides Goals Heparin Heparin Binding Human Infection Inorganic Sulfates Institutes Iowa Lectin Ligands Link Macrolides Mass Spectrum Analysis Measurement Medicine Methodology Methods Microbiology Myocardial Infarction Nickel Oligosaccharides Paralysed Pathogenesis Pattern Pharmaceutical Preparations Platelet Factor 4 Play Polysaccharides Preparation Process Protein Binding Protein Glycosylation Proteins Reaction Reactive Arthritis Relative (related person)Research Research Personnel Resistance to infection Role Series Source Stomach Stroke Surface Surface Plasmon Resonance System Techniques Thrombocytopenia Titrations Transition Elements Universities Unspecified or Sulfate Ion Sulfates Variant analog catalyst chemical synthesis college design gastrointestinal glycosylation innovation neuromuscular novel strategies novel therapeutics prevent tool trichloroacetamide

项目摘要

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

描述（由申请人提供）：在合成碳水化合物化学的领域内，糖苷键的立体选择性形成至关重要。有效地操纵键连通性在近方中心开辟了合成复杂碳水化合物的新方法，包括1,2-CIS-2-氨基糖苷。这些氨基糖构成了最重要的天然发生的寡糖和糖缀合物之一，它们是凝集素，抗体和酶的细胞表面受体配体至关重要的作用。但是，由于从天然来源获得足够定义明确的糖苷的巨大挑战，朝着理解1,2-CIS-2-氨基糖的特定功能的进展受到了阻碍。在许多情况下，高纯度1,2-CIS-2-氨基糖只能通过化学合成获得，该化学合成也可以访问结构变体。尽管在1,2-CIS-2-氨基糖苷的合成中取得了显着进步，但当前方法的缺点包括使用过量激活剂和无法预测的/差的异常选择性。在此赠款申请中，我们的目标是通过过渡金属催化的A-选择性糖基化有效合成1,2-CIS-2-氨基糖苷的新创新策略（特定目标1）。当前在我们小组中正在开发的方法将广泛适用，并以高产量和出色的A-选择性提供产品。该方法的成功完成将在碳水化合物领域产生广泛的影响，在碳水化合物场中，仍然缺乏立体选择性糖基化的催化方法。 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具有有效抗凝活性和最小副作用的寡糖（特定目标3）。 1