Počet záznamů: 1  

Enantioselective resolution of side-chain modified gem-difluorinated alcohols catalysed by Candida antarctica lipase B and monitored by capillary electrophoresis

  1. 1.
    0503710 - UOCHB-X 2020 RIV GB eng J - Článek v odborném periodiku
    Pomeisl, Karel - Lamatová, Nikola - Šolínová, Veronika - Pohl, Radek - Brabcová, Jana - Kašička, Václav - Krečmerová, Marcela
    Enantioselective resolution of side-chain modified gem-difluorinated alcohols catalysed by Candida antarctica lipase B and monitored by capillary electrophoresis.
    Bioorganic & Medicinal Chemistry. Roč. 27, č. 7 (2019), s. 1246-1253. ISSN 0968-0896
    Grant CEP: GA ČR(CZ) GA14-00522S; GA ČR(CZ) GA17-10832S; GA ČR(CZ) GA18-02597S
    Institucionální podpora: RVO:61388963
    Klíčová slova: acyclic nucleoside phosphonates * Candida antarctica lipase * capillary electrophoresis * enantioselective resolution * enzyme catalysis * gem-difluorinated alcohols * isomerisation * transesterification
    Kód oboru RIV: CC - Organická chemie
    Obor OECD: Organic chemistry
    Impakt faktor: 2.802, rok: 2018

    An enzymatic alternative to the chemical synthesis of chiral gem-difluorinated alcohols has been developed. The method is highly effective and stereoselective, feasible at laboratory temperature, avoiding the use of toxic heavy metal catalysts which is an important benefit in medicinal chemistry including the synthesis of drugs and drug precursors. Candida antarctica lipases A and B were applied for the enantioselective resolution of side-chain modified gem-difluorinated alcohols, (R)- and (S)-3-benzyloxy-1,1-difluoropropan-2-ols (1a and 1b), compounds serving as chiral building blocks in the synthesis of various bioactive molecules bearing a gem-difluorinated grouping. The catalytic activity of these lipases was investigated for the chiral acetylation of 1a and 1b in non-polar solvents using vinyl acetate as an acetyl donor. The dependence of the reaction course on various substrate and enzyme concentrations, reaction time, and temperature was monitored by chiral capillary electrophoresis (CE) using sulfobutyl ether beta-cyclodextrin as a stereoselective additive of the aqueous background electrolyte. The application of CE, NMR, and MS methods has proved that the complex enzyme effect of Candida antarctica lipase B leads to the thermodynamically stable (S)-enantiomer 1b instead of the expected acetylated derivatives. In contrast, the enantioselective acetylation of racemic alcohol 1 was observed as a kinetically controlled process, where (R)-enantiomer 1a was formed as the main product. This process was followed by enzymatic hydrolysis and chiral isomerisation. Finally, single pure enantiomers 1a and 1b were isolated and their absolute configurations were assigned from NMR analysis after esterification with Mosher's acids.
    Trvalý link: http://hdl.handle.net/11104/0296678