Our goal is to bridge the cutting-edge chiral organometallic catalysis and the current synthetic challenges at the forefront of medicinal chemistry, pharmaceutics, and pharmaceutical industry.
The core synthetic technology we use is dynamic kinetic resolution coupled to ruthenium- or rhodium- catalyzed asymmetric transfer hydrogenation (DKR-ATH) which is used in synergy with in silico drug design and in-house evaluation of physicochemical properties and biological activity to answer the actual synthetic needs of medicinal chemistry. This approach offers an integrated access to new chiral bioactive compounds with increased three-dimensionality, and increased fraction of sp3 carbon atoms which correlate with improved clinical success of the drug candidates. Moreover, we recently discovered a new class of compounds that readily form chiral organic single-component elastically or plastically flexible crystals. This will expand the scope of applications to materials science, in particular drug delivery systems.
KEY PAPERS:
CHEN, T et al. Dynamic kinetic resolution of β-substituted α-diketones via asymmetric transfer hydrogenation. Journal of the American Chemical Society 2023, 145, 585–599, DOI: 10.1021/jacs.2c11149.
STERLE, M et al. Hydrogen-bonding ability of Noyori–Ikariya catalysts enables stereoselective access to 1−CF3-substituted syn-1,2-diols via dynamic kinetic resolution. ACS Catalysis 2023, 13, 6242–6248, DOI: 10.1021/acscatal.3c00980.
COTMAN, AE et al. Catalytic stereoconvergent synthesis of homochiral β−CF3, β−SCF3, and β−OCF3 benzylic alcohols. ACS Organic & Inorganic Au. 2022, 2, 396–404, DOI: 10.1021/acsorginorgau.2c00019.
COTMAN, AE. Escaping from Flatland : stereoconvergent synthesis of 3-dimensional scaffolds via ruthenium(II)-catalyzed Noyori-Ikariya transfer hydrogenation. Chemistry – A European Journal 2021, 27, str. 39–53, DOI: 10.1002/chem.202002779.
COTMAN, AE et al. Stereoarrayed CF3-Substituted 1,3-Diols by Dynamic Kinetic Resolution: Ruthenium(II)-Catalyzed Asymmetric Transfer Hydrogenation. Angewandte Chemie 2016, 128, 5380–5380.
