Počet záznamů: 1
Enantioselective resolution of side-chain modified gem-difluorinated alcohols catalysed by Candida antarctica lipase B and monitored by capillary electrophoresis
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SYSNO ASEP 0503710 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Enantioselective 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, ORCID
Pohl, Radek (UOCHB-X) RID, ORCID
Brabcová, Jana (UOCHB-X) RID
Kašička, Václav (UOCHB-X) RID, ORCID
Krečmerová, Marcela (UOCHB-X) RID, ORCIDZdroj.dok. Bioorganic & Medicinal Chemistry. - : Elsevier - ISSN 0968-0896
Roč. 27, č. 7 (2019), s. 1246-1253Poč.str. 8 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova acyclic nucleoside phosphonates ; Candida antarctica lipase ; capillary electrophoresis ; enantioselective resolution ; enzyme catalysis ; gem-difluorinated alcohols ; isomerisation ; transesterification Vědní obor RIV CC - Organická chemie Obor OECD Organic chemistry CEP GA14-00522S GA ČR - Grantová agentura ČR GA17-10832S GA ČR - Grantová agentura ČR GA18-02597S GA ČR - Grantová agentura ČR Způsob publikování Omezený přístup Institucionální podpora UOCHB-X - RVO:61388963 UT WOS 000461168400007 EID SCOPUS 85061619987 DOI 10.1016/j.bmc.2019.02.022 Anotace 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. Pracoviště Ústav organické chemie a biochemie Kontakt asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Viktorie Chládková, Tel.: 232 002 434 Rok sběru 2020 Elektronická adresa https://www.sciencedirect.com/science/article/pii/S0968089618318169?via%3Dihub
Počet záznamů: 1