Novel Avenues to Nucleoside Modification via Catalysis Methods

该项目致力于开发碳氮和碳碳键形成的催化方法。乙烯基碳的立体控制芳基化和核苷修饰和其他应用的新配体的发展将进行审查。溶液化学将转化为聚合物支持的类似物，使用无迹连接方法进行高通量，多样性导向的研究。钯催化的方法嵌入新的生物重要的天然产物结构到核苷核心也将进行审查。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内形成C-N键，将提供新的结构基元并提供无法获得的立体控制。在有机和大分子化学项目的支持下，纽约市立大学化学系的Mahesh K. Lakshman教授正在开发新的催化反应，用于控制和有效地合成修饰核苷。修饰核苷具有很高的重要性和价值，在新发疾病和现有疾病的新药物、生物分子功能探针和分子自组装的新范式等方面有着广泛的应用。这些反应将使用钯催化，一种强大的有机合成方法来实现。钯催化反应和核苷化学的融合有望导致新的和不寻常的结构基序，具有广泛的潜在应用。

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.