De Novo Synthesis of Oligosaccharides

低聚糖的从头合成

• 批准号: 8330298
• 负责人: GEORGE A O'DOHERTY
• 金额: $ 30.48万
• 依托单位: NORTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8330298
• 关键词: Acquired Immunodeficiency Syndrome; Address; Adhesions; Amino Sugars; Anti-Infective Agents; Area; Belief; Biological; Biological Process; Biology; Carbohydrates; Catalysis; Chemistry; Complex; Coupled; Deoxy Sugars; Development; Disease; Energy Supply; Enzymes; Event; Galactose; Glucose; Glycoside Hydrolases; Goals; Infection; Inorganic Sulfates; Laboratories; Mannose; Methodology; Methods; Modification; Molecular; Monosaccharides; Oligonucleotides; Oligosaccharides; Palladium; Peptides; Pharmaceutical Chemistry; Pharmaceutical Preparations; Pharmacologic Substance; Play; Positioning Attribute; Predisposition; Preparation; Procedures; Property; Reaction; Research; Rhamnose; Role; Scheme; Structure; Synthesis Chemistry; Tuberculosis; Universities; Unspecified or Sulfate Ion Sulfates; Vaccines; West Virginia; Work; analog; base; cancer therapy; carbohydrate analog; functional group; glycosylation; improved; lipomannan; microbial; microorganism; mimetics; new technology; novel; sugar

Project Summary The overall objective of this proposal renewal is to continue our development of an efficient and general strategy for the asymmetric synthesis of oligosaccharides (X = O) and to expand it to the synthesis of analogous oligo-cyclitols (X = CH2, Scheme 1). The method we propose has the potential to revolutionize the way oligosaccharides are synthesized. Our method revolves around the use of a highly stereoselective palladium catalyzed glycosylation (X = O: 2.1¿/2.4¿ to 2.2 ¿/2.5¿) and cyclitolization (X = CH2; Scheme 1). There has been an astounding amount of research directed toward the synthesis of oligosaccharides; however, when it comes to unnatural oligosaccharides, the current state of the art is lacking. This deficiency is undoubtedly due to the limited number of carbohydrate starting materials (glucose, mannose, and galactose). A complementary approach would be to start with a significantly simplified structure and to sequentially increase its stereochemical and functional complexity to a range of structures (eg., 1.5/1.6 to 1.1-1.3; Scheme 1). The underlying hypothesis that guides our synthetic approach is the belief that there are many carbohydrate analogs, which remain undiscovered because of synthetic limitations. Thus, we believe a methodology that allows for the facile incorporation of simple sugars (i.e. under-functionalized) into oligosaccharide motifs will drastically enable the discovery of new structures with a wide range of functions.

项目摘要 该提案更新的总体目标是继续我们发展有效，一般的 寡糖不对称合成（X = O）的策略，并将其扩展为合成 类似的寡核糖醇（X = CH2，方案1）。我们提出的方法有可能革新 寡糖合成的方式。我们的方法围绕使用高度立体选择性 钯催化的糖基化（X = O：2.1¿/2.4€to2.2¿/2.5？）和环醇（X = CH2;方案1）。 针对寡糖的合成，已经有大量的研究。 但是，当涉及到不自然的寡糖时，目前缺乏艺术的状态。这种缺陷是 毫无疑问，由于碳水化合物的起始材料（葡萄糖，甘露糖和半乳糖）数量有限。 一种完整的方法是从显着简化的结构开始，然后依次 将其立体化学和功能复杂性增加到一系列结构（例如，1.5/1.6至1.1-1.3;方案 1）。指导我们合成方法的基本假设是相信有许多碳水化合物 由于合成的局限性，类似物仍然未被发现。那就是我们相信一种方法论 允许将简单的糖保险（即功能不足）纳入寡糖图案 大幅度地使发现具有广泛功能的新结构。