ABSTRACT
A mild calcium catalysed Beckmann rearrangement has been realised, which forgoes the more traditional harsh reactions conditions associated with the transformation. The catalyst system is shown to be tolerant towards a wide variety of functional groups relevant to natural product synthesis and medicinal chemistry and the synthetic utility of the reaction has also been investigated. A preliminary mechanistic investigation was performed to understand the nature of the incoming nucleophile and a possible reaction pathway is described.
Subject(s)
Cell Proliferation/physiology , Glioblastoma/metabolism , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Protein Serine-Threonine Kinases/antagonists & inhibitors , Cell Proliferation/drug effects , Glioblastoma/drug therapy , Humans , Intracellular Signaling Peptides and Proteins/pharmacology , Protein Serine-Threonine Kinases/pharmacologyABSTRACT
There is interest in developing potent, selective, and cell-permeable inhibitors of human ferrous iron and 2-oxoglutarate (2OG) oxygenases for use in functional and target validation studies. The 3-component Betti reaction enables efficient one-step C-7 functionalisation of modified 8-hydroxyquinolines (8HQs) to produce cell-active inhibitors of KDM4 histone demethylases and other 2OG oxygenases; the work exemplifies how a template-based metallo-enzyme inhibitor approach can be used to give biologically active compounds.
