Novel Avenues to Nucleoside Modification via Catalysis Methods

该项目致力于开发形成碳-氮键和碳-碳键的催化方法。将研究乙烯碳的立体控制芳基化和核苷修饰和其他应用的新配体的开发。溶液化学将被翻译为聚合物支持的类似物，使用无痕接头的方法进行高通量，多样性导向的研究。钯催化的方法嵌入到核苷核心的新的生物学上重要的天然产物结构也将被检查。钯和铜或钯和钌的互补催化，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，将提供新的结构基序，并提供立体控制，否则无法实现。纽约市立大学化学系的Lakshman正在开发新的催化反应，适用于控制和有效合成修饰核苷。修饰的核苷具有很高的重要性和价值，具有广泛的应用范围，从针对新出现的疾病以及现有疾病的新药理学试剂，生物分子功能的探针和分子自组装背景下的新范例。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.