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.
    SYSNO ASEP0503710
    Druh ASEPJ - Článek v odborném periodiku
    Zařazení RIVJ - Článek v odborném periodiku
    Poddruh JČlánek ve WOS
    NázevEnantioselective resolution of side-chain modified gem-difluorinated alcohols catalysed by Candida antarctica lipase B and monitored by capillary electrophoresis
    Tvůrce(i) Pomeisl, Karel (UOCHB-X) RID
    Lamatová, Nikola (UOCHB-X)
    Šolínová, Veronika (UOCHB-X) RID
    Pohl, Radek (UOCHB-X) RID
    Brabcová, Jana (UOCHB-X) RID
    Kašička, Václav (UOCHB-X) RID
    Krečmerová, Marcela (UOCHB-X) RID
    Zdroj.dok.Bioorganic & Medicinal Chemistry. - : Elsevier - ISSN 0968-0896
    Roč. 27, č. 7 (2019), s. 1246-1253
    Poč.str.8 s.
    Jazyk dok.eng - angličtina
    Země vyd.GB - Velká Británie
    Klíč. slovaacyclic nucleoside phosphonates ; Candida antarctica lipase ; capillary electrophoresis ; enantioselective resolution ; enzyme catalysis ; gem-difluorinated alcohols ; isomerisation ; transesterification
    Vědní obor RIVCC - Organická chemie
    Obor OECDOrganic chemistry
    CEPGA14-00522S GA ČR - Grantová agentura ČR
    GA17-10832S GA ČR - Grantová agentura ČR
    GA18-02597S GA ČR - Grantová agentura ČR
    Institucionální podporaUOCHB-X - RVO:61388963
    UT WOS000461168400007
    EID SCOPUS85061619987
    DOI10.1016/j.bmc.2019.02.022
    AnotaceAn 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.
    PracovištěÚstav organické chemie a biochemie
    KontaktJana Procházková, janap@uochb.cas.cz, Tel.: 220 183 418 ; Viktorie Chládková, viktorie.chladkova@uochb.cas.cz, Tel.: 232 002 434
    Rok sběru2020