Studies of oxygen-containing organic compounds

含氧有机化合物的研究

• 批准号: 9912-2006
• 负责人: Grindley, Bruce
• 金额: $ 3.5万
• 依托单位: Dalhousie University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2007
• 资助国家: 加拿大
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=365875
• 关键词: Studies; oxygen; containing; organic; compounds

This application is divided into three areas all of which involve oxygen-containing organic compounds.  The first of these deals with the interactions of cell surface carbohydrates with proteins.  Cell surfaces are covered by carbohydrate chains that are involved in recognition of proteins through interactions that are normally weak.  One medically significant example is the attachment of the uropathegenic bacteria E. coli to the surface of the intestinal tract which takes place through binding of protein on threads projecting from the bacterial surface to carbohydrates on the tissue surface.  It is proposed to synthesize two classes of large molecules (dendrimers), including one new class, that are able to present multiple copies of the sugar that will interfere with this binding.  Another example of interest is the protein DC-SIGN present on certain human tissues, that is thought to be involved in bringing a variety of pathogens into the body including viruses (HIV, hepatitis C), bacteria, yeasts and parasites.  Binding to surface carbohydrates on the pathogen is the initial step in this process that could be disrupted by competing binding agents, such as variants on the dendrimers proposed above having appropriate geometries.  A second area involves the synthesis of the repeating unit of the common antigen of all Streptococcus pneumoniae serotypes, the C-polysaccharide, segments of this repeating unit, and oligomers of the repeating unit.  Larger compounds in which these compounds are attached to dendrimers and/or proteins will be evaluated as vaccines.  A third part of the application contains a proposal to continue the investigation of several aspects of the very useful stannylene reaction both computationally and experimentally in order to understand why it gives regioselective reactions.  This improved understanding should lead to the synthesis of alternative dialkyltin alkoxides that give improved and more controlled regioselectivity in substitution of diols and polyols which would be generally useful for the synthesis of substituted carbohydrates and other compounds containing multiple hydroxyl groups.

这种应用分为三个领域，都涉及到含氧有机化合物。第一个是细胞表面碳水化合物与蛋白质的相互作用。细胞表面覆盖着碳水化合物链，这些碳水化合物链通过通常较弱的相互作用参与蛋白质的识别。一个医学上重要的例子是尿路致病菌大肠杆菌附着在肠道表面，这是通过从细菌表面伸出的线上的蛋白质与组织表面的碳水化合物结合而发生的。有人建议合成两类大分子（树状大分子），包括一种新的类，它们能够提供干扰这种结合的糖的多个拷贝。另一个有趣的例子是存在于某些人体组织中的蛋白质DC-SIGN，它被认为参与将各种病原体带入人体，包括病毒（艾滋病毒、丙型肝炎）、细菌、酵母和寄生虫。与病原体表面碳水化合物的结合是这一过程的第一步，这一过程可能会被竞争性的结合剂所破坏，比如上面提出的具有适当几何形状的树状大分子的变体。第二个领域涉及所有肺炎链球菌血清型共同抗原重复单元、c -多糖、该重复单元的片段和重复单元的低聚物的合成。较大的化合物，其中这些化合物附着在树突和/或蛋白质上，将被评估为疫苗。该申请的第三部分包含了继续研究非常有用的锡炔反应的几个方面的建议，包括计算和实验，以理解为什么它会产生区域选择性反应。这种认识的提高将导致替代二烷基锡烷氧化物的合成，这种替代二醇和多元醇具有更好和更可控的区域选择性，这对于替代碳水化合物和其他含有多个羟基的化合物的合成通常是有用的。