ABSTRACT
Based upon observations from our initial findings, additional myxopyronin B analogs have been prepared and tested for in vitro inhibitory activity against DNA-dependent RNA polymerase and antibacterial activity against Escherichia coli and Staphylococcus aureus.
Subject(s)
DNA-Directed RNA Polymerases/antagonists & inhibitors , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Lactones/chemistry , Lactones/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , DNA-Directed RNA Polymerases/metabolism , Enzyme Inhibitors/chemistry , Escherichia coli/drug effects , Escherichia coli/enzymology , Inhibitory Concentration 50 , Lactones/chemical synthesis , Methylation , Molecular Structure , Staphylococcus aureus/drug effects , Staphylococcus aureus/enzymologyABSTRACT
We have developed proline-catalyzed direct asymmetric three-component Mannich reactions of ketones, aldehydes, and amines. Several of the studied reactions provide beta-amino carbonyl compounds (Mannich products) in excellent enantio-, diastereo-, regio-, and chemoselectivities. The scope of each of the three components and the influence of the catalyst structure on the reaction are described. Reaction conditions have been optimized, and the mechanism and source of asymmetric induction are discussed. We further present application of our reaction to the highly enantioselective synthesis of 1,2-amino alcohols.
