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Synthesis and HHDH-catalyzed kinetic resolution of propargylic epoxides

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Názov: Synthesis and HHDH-catalyzed kinetic resolution of propargylic epoxides
Autori: Majerić-Elenkov, Maja, Dokli, Irena, Kolman, Robert Junior, Švaco, Petra
Informácie o vydavateľovi: 2024.
Rok vydania: 2024
Predmety: biocatalysis, halohydrin dehalogenases, kinetic resolution, propargylic epoxides
Popis: The versatile reactivity of propargylic epoxides and alcohols, due to the presence of a triple bond, is used in the synthesis of various organic compounds and building blocks.1 However, there are not many known methods for the preparation of optically pure propargylic epoxides and alcohols, and the existing ones often require specific reagents.1 Halohydrin dehalogenases (HHDHs) can be used to obtain enantiomerically pure compounds from racemic epoxides.2 These important biocatalysts facilitate epoxide ring-opening reactions with unnatural nucleophiles such as azides. Here we report the biocatalytic transformation of propargylic epoxides using HHDHs. Six propargylic epoxides with different substituents were synthesized. Kinetic resolution reactions catalyzed by HHDHs in the presence of azide were performed. Two enzymes with opposite stereoselectivities, HheC and HheA2-N178A were used and yielded azido alcohols (98 - >99% ee, E-value >200) and epoxides (29 - 88% ee). The best performing p-tolyl propargylic epoxide derivative was used in a sequence of two enzymatic reactions to obtain both enantiomers of the β-azido alcohol and the (R)-enantiomer of the α-azido alcohol, each in >99% ee, through complete conversion of the starting epoxide.3 The obtained azido alcohols were used in the click reactions with terminal acetylenes to obtain optically pure triazolyl propargylic alcohols.
Druh dokumentu: Conference object
Prístupová URL adresa: https://solutionsinchemistry.hkd.hr/sic_boa/
Prístupové číslo: edsair.dris...01492..2c69908a5b2176e7e07da7bf3a20187d
Databáza: OpenAIRE
Popis
Abstrakt:The versatile reactivity of propargylic epoxides and alcohols, due to the presence of a triple bond, is used in the synthesis of various organic compounds and building blocks.1 However, there are not many known methods for the preparation of optically pure propargylic epoxides and alcohols, and the existing ones often require specific reagents.1 Halohydrin dehalogenases (HHDHs) can be used to obtain enantiomerically pure compounds from racemic epoxides.2 These important biocatalysts facilitate epoxide ring-opening reactions with unnatural nucleophiles such as azides. Here we report the biocatalytic transformation of propargylic epoxides using HHDHs. Six propargylic epoxides with different substituents were synthesized. Kinetic resolution reactions catalyzed by HHDHs in the presence of azide were performed. Two enzymes with opposite stereoselectivities, HheC and HheA2-N178A were used and yielded azido alcohols (98 - >99% ee, E-value >200) and epoxides (29 - 88% ee). The best performing p-tolyl propargylic epoxide derivative was used in a sequence of two enzymatic reactions to obtain both enantiomers of the β-azido alcohol and the (R)-enantiomer of the α-azido alcohol, each in >99% ee, through complete conversion of the starting epoxide.3 The obtained azido alcohols were used in the click reactions with terminal acetylenes to obtain optically pure triazolyl propargylic alcohols.