Chemical Synthesis of Beta-Manno and Rehamnopyranosides

β-甘露糖苷和吡喃大黄苷的化学合成

• 批准号: 7091223
• 负责人: David Crich
• 金额: $ 29.17万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7091223
• 关键词: Escherichia; Streptococcus pneumoniae; bacterial capsules; bacterial polysaccharides; carbohydrate structure; chemical bond; chemical synthesis; conformation; glycosides; hexoses; mannose; polymerization; pyrans; stereochemistry; stereoisomer

DESCRIPTION (provided by applicant): Contemporary carbohydrate chemistry is being continually challenged by the ever expanding field of glycobiology and, more specifically, by the complexity and diversity of biologically and medically important oligosaccharides uncovered whose synthesis is mandated by their extremely tedious isolation and purification from natural sources in minute quantities. Great strides forward have been made such that the automated synthesis of some of the more straightforward oligosaccharides is now a reality and potential carbohydrate-based antitumor vaccines have been produced by solution phase synthesis on such a scale as to enable clinical trials. A fully synthetic pentasaccharide is now a commercial antithrombotic drug in Europe. Smaller oligosaccharide chains have a profound effect on the biology of many drugs, often in ways not yet fully understood. In spite of these and other remarkable advances, many of which could not have been contemplated a few years ago, there still remain many important problems in carbohydrate chemistry to be addressed before the full potential of glycobiology can even begin to be realized. The aims of this project are to provide enabling chemistry for the direct, stereo-controlled synthesis of some of the more complex types of glycosidic bond found in biology and to illustrate these methods through the total synthesis of specific structures of biological significance. We focus our efforts in this project on the 1,2-cis-equatorial bonds to pyranosides. The most common form of this linkage type is the beta-D-mannopyranoside linkage, although various deoxy forms are also widespread, including the beta-rhamnopyranosides. In macrolide antibiotics this type of glycosidic bond makes it appearance in the form of beta-glycosidic bonds to mycosamine, that is of 3,6-dideoxy-3-amino-beta-mannosides. More recently, the core O-specific IPS from Plesimonas Shigelloides O54 has been found to contain two unusual beta-linked heptopyranosides having the D-glycero-D- manno and 6-deoxyglycero-D-manno configuration. The chemistry described in this proposal has the specific aim of making the synthesis of the 1,2-cis- equatorial glycosidic bonds practical, and efficient, putting it on a similar footing to that of oligonucleotides and peptides, and of demonstrating this through the synthesis of suitably complex, biologically-active oligosaccharides.

描述（由申请人提供）：当代碳水化合物化学正不断受到糖生物学领域不断扩大的挑战，更具体地说，受到生物学和医学上重要的寡糖的复杂性和多样性的挑战，这些寡糖的合成是通过极其繁琐的分离和从微量的自然来源中纯化出来的。已经取得了巨大的进步，一些更直接的低聚糖的自动合成现在已经成为现实，潜在的基于碳水化合物的抗肿瘤疫苗已经通过液相合成生产出来，规模如此之大，以至于能够进行临床试验。一种完全合成的五糖现在是欧洲的商业抗血栓药物。较小的寡糖链对许多药物的生物学有深远的影响，通常以尚未完全了解的方式。尽管有了这些和其他显著的进展，其中许多是几年前无法想象的，但在糖生物学的全部潜力开始实现之前，碳水化合物化学中仍有许多重要的问题需要解决。该项目的目的是为直接、立体控制合成生物学中发现的一些更复杂类型的糖苷键提供化学支持，并通过具有生物学意义的特定结构的总合成来说明这些方法。在这个项目中，我们将重点放在吡苷的1,2-顺赤道键上。这种连接类型最常见的形式是β - d -甘露糖吡喃苷连接，尽管各种脱氧形式也很普遍，包括β -鼠李糖吡喃苷。在大环内酯类抗生素中，这种类型的糖苷键使其以-糖苷键的形式出现在真菌胺上，即3,6-二脱氧-3-氨基- -甘露糖苷。最近，从shiigelloides Plesimonas O54提取的核心o特异性IPS被发现含有两种不寻常的β -连接的庚嘌呤苷，它们具有d -甘油-d -甘露糖和6-脱氧甘油-d -甘露糖结构。