Studies of oxygen-containing organic compounds

该应用分为三个领域，所有这些领域都涉及含氧有机化合物。 其中第一个涉及细胞表面碳水化合物与蛋白质的相互作用。 细胞表面被碳水化合物链覆盖，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致尿路病细菌E.大肠杆菌粘附到肠道表面，这是通过从细菌表面伸出的细丝上的蛋白质与组织表面上的碳水化合物结合而发生的。 有人建议合成两类大分子（树枝状聚合物），包括一类新的，能够呈现多个拷贝的糖，这将干扰这种结合。 另一个感兴趣的例子是存在于某些人体组织上的蛋白DC-SIGN，它被认为参与将各种病原体带入体内，包括病毒（HIV，丙型肝炎），细菌，酵母和寄生虫。 与病原体上的表面碳水化合物的结合是该过程中的初始步骤，其可以被竞争结合剂破坏，例如上面提出的具有适当几何形状的树枝状聚合物上的变体。 第二个领域涉及所有肺炎链球菌血清型的共同抗原的重复单元、C-多糖、该重复单元的片段和重复单元的寡聚体的合成。 其中这些化合物与树枝状聚合物和/或蛋白质连接的较大化合物将作为疫苗进行评价。 第三部分的应用程序包含一个建议，继续调查的几个方面非常有用的stannylene反应的计算和实验，以了解为什么它给区域选择性反应。 这种改进的理解应导致合成替代的二烷基锡醇盐，其在二醇和多元醇的取代中提供改进的和更受控的区域选择性，其通常可用于合成取代的碳水化合物和含有多个羟基的其它化合物。

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.