Part I. Development of new organic synthetic methods: Palladium and copper catalyzed carbon-carbon, carbon-sulfur, carbon-nitrogen, and carbon-oxygen bond formation as well as DABCO-mediated stereospecific synthesis of acrylate ethers and amines. Part II. Design, synthesis and SAR studies of new classes of agents to treat drug-resistant bacteria, anthrax and tuberculosis infections.

摘要

Part 1: Chapter 1. Development of A Very Active Cu-Catalytic System for the Stereo- and Regiospecific Synthesis of Vinyl Sulfides as well as the Synthesis of Aryl and Heteroaryl Sulfides. cis-1,2-Cyclohexanediol (L3) has been shown to be an efficient and versatile bidentate O-donor ligand that provides a highly active Cu-catalytic system and hence it is reported. It was more effective than diols such as trans-1,2-cyclohexanediol or ethylene glycol.;Chapter 2. Development of An Imidazole-based Ligand Based Cu-Catalytic Method for Efficient Copper-Catalyzed C-N and C-0 Bond Forming Cross-Coupling Reactions for the Synthesis of Vinyl Amines and Ethers as well as Their Respective Aryl Derivatives. 2-Pyridin-2-yl-1H-benzoimidazole is presented as an efficient and versatile bidentate N-donor ligand for the copper catalyzed formation of vinyl and aryl C-N and C0 bonds. This inexpensive and easily prepared ligand facilitates copper-catalyzed cross-coupling reactions of alkenyl and aryl halides with N-heterocycles and phenols to afford the desired cross-coupled products in good to excellent yield.;Chapter 3. Development of A Stereospecific enolate-driven Cu-Catalytic Method for Carbon-Carbon Bond Forming Reactions. A new process for this stereocontrolled intramolecular cross-coupling has been developed via a copper-mediated process. The initial results of this investigation indicated that an enolate driven palladium-mediated cross-coupling reaction can be accomplished by a copper-mediated process which is less expensive and much easier to work-up. This method could be applied to synthesize several complex indole alkaloids.;Chapter 4. Development of A Base DABCO (1,4-diazabicyclo[2:2.2]-octane) Mediated Method for the Stereospecific Synthesis of Ethyl Acrylate Ethers and Amines. A functionalized alkenyl iodide, ethyliodo acrylate, was tested for the coupling reaction with phenols and N-heterocycles using metal catalyzed processes which proved to be ineffective for both nucleophiles phenols and N-heterocycles. The products obtained in case of ethyliodo acrylate substrate, presumably, resulted from 1,4-Michael addition reaction, which gave the mixtures of cis and trans isomers of the desired products ethers or amines from cis-iodo-acrylate at room temperature instead of the metal mediated stereospecific cross-coupled products.;Chapter 5. Development of An Efficient Palladium Catalyzed Negishi Cross-Coupling Reaction with Aryl Vinyl Iodides: Facile Regioselective Synthesis of E-Stilbenes and Their Analogues. A general synthetic route for the Pd-catalyzed cross-coupling of an arylzinc reagent with arylvinyl iodides (Negishi cross-coupling) has been developed. The system permits efficient and selective preparation of E-stilbenes and their analogues. It also functions effectively at low levels of catalyst loading without the need for an additional ligand and tolerates a wide range of functional groups including heteroaromatic activity.;Chapter 6. Development of An Efficient Palladium Catalyzed Two Step Synthesis of BzR/GABERgic Active Flavones via A Wacker-Cook Related Oxidation. A general route for the synthesis of biologically important flavones is reported via a two step sequence employing a catalytic Wacker-Cook oxidation 4b as the key step.;Part II: Chapter 7. Discovery of a Novel Lead Antibacterial Agent for the Potential Treatment of Broad-Spectrum Gram-Positive Bacterial Infections Including Vancomycin-Resistant Enterococci (VRE),Methicillin-Resistant Staphylococcus aureus (MRSA) and Anthrax. An antimicrobial phenolic stilbene, (E)-3-hydroxy-5-methoxystilbene, was recently isolated from the leaves of Comptonia peregrina (L.) Coulter and shown to possess inhibitory activity against several Gram-positive bacteria, including isolates of methicillin-resistant Staphylococcus aureus (MRSA), Mycobacterium bovis BCG, and avirulent Bacillus anthracis (Sterne strain), among others.;Chapter 8. A New Class of Potential Anti-Tuberculosis Agents: Synthesis and Preliminary Evaluation of Novel Acrylic Acid Ethyl Ester Derivatives. Novel acrylic acid ethyl ester derivatives were synthesized and evaluated as potential agents against Mycobacterium species. A versatile and efficient copper-catalyzed and base mediated coupling process were developed and used to prepare a library of substituted acrylic acid ethyl ester analogs. (Abstract shortened by UMI.).