New Strategies for Glycoconjugate Synthesis

糖复合物合成的新策略

• 批准号: 6759412
• 负责人: Frank Edward McDonald
• 金额: $ 32.15万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-04-07 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6759412
• 关键词: biological products; carbohydrates; chemical synthesis; glycolipids; glycoproteins; glycosidases; glycosylation; method development; stereochemistry

DESCRIPTION (provided by applicant): This competing continuation application describes the invention and application of novel chemical transformations for the preparation of structurally unusual carbohydrates and oligosaccharides, which are important structural components of many compounds that exhibit anticancer, antimicrobial, and immunostimulating activities. Specific chemical transformations developed by the P.l.'s laboratory which will be applied in this research include the catalytic endoselective alkynol cycloisomerization reaction, as well as electrophile-promoted glycosylations including the conceptually simple but underexploited acid-catalyzed glycosylation for the synthesis of 2-deoxyglycosides. Other metal-catalyzed processes such as internally directed Heck reactions will also be utilized in the construction of branched glycosides. These transformations are the basis for unique strategies to the syntheses of O- and C-linked oligosaccharides which have many advantages over classical methods. For instance, the efficient stereoselective synthesis of alkynyl alcohol substrates is easily applied to the construction of oligosaccharides bearing unusual stereochemical and substitution patterns, as well as the highly deoxygenated oligosaccharides present in many compounds exhibiting anticancer and other therapeutic properties. Specific aims for the next funding period include continued methodology development for siteselective and stereoselective transformations of the glycal products obtained from alkynol cycloisomerization, in the context of projects directed at: (1) synthesis of trisaccharide natural products bearing beta-glycosides of 2,6-dideoxyglycosides of the arabino configuration (i.e. maryal); (2) synthesis of the altromycin C-glycoside family of antitumor antibiotics, including determination of unassigned elements of absolute and relative stereochemistry; and (3) partial synthesis of degradation products of the antibiotic saccharomicin natural products, including determination of absolute stereochemistry of the individual sugar components.

描述（由申请人提供）：这种竞争连续申请描述了新型化学转化的发明和应用，用于制备结构不寻常的碳水化合物和寡糖，这些碳水化合物和寡糖是许多表现出抗癌，抗药性和免疫刺激活性的许多化合物的重要结构成分。 P.L.的实验室开发的特定化学转化将在本研究中应用，包括催化性内染色性藻醇环化体反应以及电力促进的糖基化，包括概念上简单但无流水的酸性糖基化的糖基化，以用于2-二氧化脱氧糖的合成。其他金属催化的过程，例如内部定向的HECK反应也将用于构造分支糖苷。这些转换是对O-和C连锁寡糖合成的独特策略的基础，这些寡糖比经典方法具有许多优势。例如，有效地将藻类酒精底物的有效立体选择合成用于构建具有异常立体化学和替代模式的寡糖，以及许多具有抗癌药物和其他治疗特性的高度脱氧寡糖。 在下一个资金期间的具体目的包括在针对以下项目的项目的背景下，从烷基诺醇环异构化获得的甘表示甘油产物的站点和立体选择性转换的方法开发。 （1）含有β-糖苷的三糖天然产物的合成，其β-糖苷是2,6-二维糖苷的阿拉比尼构型（即玛丽尔）； （2）抗肿瘤抗生素的多霉素C-糖苷家族的合成，包括确定绝对和相对立体化学的未分配元素；和 （3）部分合成抗生素糖含量天然产物的降解产物，包括确定单个糖成分的绝对立体化学。