Novel Avenues to Nucleoside Modification via Catalysis Methods

该项目致力于开发形成碳-氮和碳-碳键的催化方法。本课程将考察乙烯基碳的立体控制芳基化反应，以及用于核苷修饰和其他应用的新配体的开发。溶液化学将被转化为聚合物支持的类似物，使用无迹链接器方法进行高通量、面向多样性的研究。还将研究钯催化的将新的具有生物重要性的天然产物结构嵌入核苷核心的方法。Pd和Cu或Pd和Ru的互补催化，其中一种特定的催化剂可用于实现C-C反应，而另一种可用于在单一底物中形成C-N键，这将提供新的结构基元并提供以其他方式无法实现的立体控制。在纽约州立大学城市学院化学系的这一奖项的支持下，纽约州立大学城市学院化学系的Mahesh K.Lakshman教授正在开发适用于受控和高效合成修饰核苷的新催化反应。修饰的核苷具有很高的重要性和价值，在针对新出现的疾病和现有疾病的新药理药物、生物分子功能的探针和分子自组装背景下的新范式等方面有着广泛的应用。这些反应将使用钯催化，这是一种强大的有机合成方法。钯催化的反应和核苷化学的融合有望产生具有广泛潜在应用的新的和不寻常的结构基序。

This project addresses the development of catalytic methods for the formation of carbon-nitrogen and carbon-carbon bonds. Stereocontrolled arylation of vinylic carbons and the development of new ligands for nucleoside modification and other applications will be examined. Solution chemistry will be translated to polymer-supported analogs using a traceless linker approach for high-throughput, diversity-oriented studies. Palladium catalyzed methods for embedding novel biologically important natural product structures into nucleoside cores will also be examined. Complementary catalysis by Pd and Cu or Pd and Ru, in which one specific catalyst can be used to achieve C-C reactions whereas another can be used for C-N bond formation within a single substrate, will provide new structural motifs and offer stereocontrol that cannot be otherwise attained.With the support of this award from the Organic and Macromolecular Chemistry Program, Professor Mahesh K. Lakshman, of the Department of Chemistry at CUNY City College, is developing new catalytic reactions applicable to the controlled and efficient synthesis of modified nucleosides. Modified nucleosides are of high importance and value, with a broad range of applications spanning from new pharmacological agents against emerging diseases as well as existing ones, probes of biomolecular function and new paradigms within the context of molecular self-assembly. These reactions will be effected using palladium catalysis, a powerful organic synthesis methodology. The confluence of palladium-catalyzed reactions and nucleoside chemistry is expected to lead to new and unusual structural motifs with wide ranging potential applications.