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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F19%3A00503710" target="_blank" >RIV/61388963:_____/19:00503710 - isvavai.cz</a>

Alternative codes found

RIV/68378271:_____/19:00511157

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S0968089618318169?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0968089618318169?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bmc.2019.02.022" target="_blank" >10.1016/j.bmc.2019.02.022</a>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10401 - Organic chemistry

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Bioorganic & Medicinal Chemistry

ISSN

0968-0896

e-ISSN

—

Volume of the periodical

27

Issue of the periodical within the volume

7

Country of publishing house

GB - UNITED KINGDOM

Number of pages

8

Pages from-to

1246-1253

UT code for WoS article

000461168400007

EID of the result in the Scopus database

2-s2.0-85061619987