Bugera M. Application of new difluoromethylene-containing building blocks for synthesis of natural amino acids analogues and nitrogen-containing heterocycles

Fluorine-containing building blocks, difluoromethylene-containing amino acids and nitrogen-containing heterocycles. Development of methods for obtaining new difluoromethylene-containing building blocks based on ethyl bromodifluoroacetate and their use to obtain promising analogues of natural amino acids and nitrogen-containing heterocycles. Organic synthesis (synthesis of chemical compounds); IR and NMR spectroscopy, chromato-mass spectrometry (establishment of structure and purity of compounds); X-ray diffraction analysis (establishment of the structure of compounds); column and ion exchange chromatography (purification of compounds); thin layer chromatography (control of the course of reactions). The conditions for the addition of ethyl bromodifluoroacetate to various alkoxyalkens have been studied. Low molecular weight fluorine-containing building blocks containing several functional groups are obtained. A convenient approach to the synthesis of previously unknown 3,3-difluoro-GABA using the interaction product of ethyl bromodifluoroacetate and ethyl vinyl ether has been developed. A convenient method for the synthesis of 2,2-difluoro-GABA through the stage of addition of ethyl bromodifluoroacetate to benzyl acrylate according to the Kumadaki method has been developed. A simple method for producing fluorinated analogs of glutamic acid and glutamine using the reaction of ethyl bromodifluoroacetate with α, β-unsaturated derivatives of α-amino acids is proposed. A number of difluoromethylene-containing enones were synthesized based on available (het)aryldifluoroacetic acids, which were used for the synthesis of new heterocyclic compounds. New functionalized building blocks were obtained by bromination of α-methyl (polyfluoroalkyl) enones in the allyl position, their properties in reactions with nucleophiles and binucleophiles were investigated. Scope - bioorganic chemistry.