Timokhin O. Enzymatic kinetic resolution in the synthesis of enantioenriched 2-substituted chroman-4-ols

2-Substituted chroman-4-ols, including their alkyl, hetaryl and fluoroalkyl derivatives, as well as the corresponding starting and intermediate substrates – chromones, chroman-4-ones, chroman-4-ols and the corresponding acetates. Development of a universal chemoenzymatic methodology for the synthesis of enantioenriched 2-substituted chroman-4-ols and their functionalized derivatives based on enzymatic kinetic resolution, as well as a comprehensive study of their spectral features, physicochemical parameters and determination of biological potential. Organic synthesis, biocatalysis, NMR spectroscopy, two-dimensional NMR spectroscopy, high-resolution mass spectrometry, high-performance liquid chromatography on chiral stationary phases, thin-layer and column chromatography, in vitro biological screening methods. Highly efficient chemoenzymatic methodologies for the synthesis of enantioenriched chroman-4-ols with various substituents in the 2nd position have been developed and implemented. The proposed approaches provide the production of target compounds with exceptional optical purity and allow scaling up biocatalytic processes to multigram quantities. A library of new enantioenriched building blocks has been created. The possibility of rational control of the ADME profile of lead compounds by introducing fluoroalkyl substituents has been experimentally proven. A promising lead compound, 7-hydroxyspiro[chroman-2,1'-cyclohexane]-4-one, has been identified. The results obtained allow us to consider this system as a strategic starting point for further structural optimization with the aim of creating new generation antiviral and antitumor drugs based on it. The scope of application is organic and medicinal chemistry