Studies of oxygen-containing organic compounds

这一应用分为三个领域，它们都涉及含氧有机化合物。第一个领域涉及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，这些碳水化合物通过通常较弱的相互作用参与识别蛋白质。一个医学上重要的例子是尿路致病菌大肠杆菌与肠道表面的附着，这是通过将蛋白质结合在从细菌表面突出的线条上与组织表面的碳水化合物发生的。建议合成两类大分子(树状大分子)，其中包括一种新的大分子，能够呈现多个副本的糖，从而干扰这种结合。另一个有趣的例子是存在于某些人类组织中的蛋白质DC-SIGN，它被认为参与将包括病毒(HIV、丙型肝炎)、细菌、酵母和寄生虫在内的各种病原体带入体内。与病原体上的表面碳水化合物的结合是这个过程的第一步，可能会被竞争的结合剂破坏，例如上面提出的具有适当几何结构的树状大分子上的变体。第二个区域涉及所有血清型链球菌共同抗原的重复单位的合成，C-肺炎多糖，这一重复单元的片段和重复单元的低聚物。这些化合物连接到树枝状大分子和/或蛋白质上的更大的化合物将被评估为疫苗。申请的第三部分包含一项建议，继续从计算和实验上研究非常有用的锡烯反应的几个方面，以了解为什么它会产生区域选择性反应。这种改进的理解应该导致合成替代的二烷基锡醇类化合物，它在取代二醇和多元醇中具有更好的和更可控的区域选择性，这将通常用于取代碳水化合物和其他含有多个羟基的化合物的合成。

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.