Asymmetric Biocatalytic Synthesis of Fluorinated Pyridines through Transesterification or Transamination: Computational Insights into the Reactivity of Transaminases
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- 作者：Marí ; a Ló ; pez-Iglesias ; Daniel Gonzá ; lez-Martí ; nez ; Marí ; a Rodrí ; guez-Mata ; Vicente Gotor ; Eduardo Busto ; Wolfgang Kroutil and Vicente Gotor-Ferná ; ndez
- 刊名：Advanced Synthesis & Catalysis
- 出版年：2017
- 出版时间：January 19, 2017
- 年：2017
- 卷：359
- 期：2
- 页码：279-291
- 全文大小：1966K
- ISSN：1615-4169
文摘
The synthesis of a family of pyridines bearing a fluorinated substituent on the aromatic ring has been carried out through two independent and highly stereoselective chemoenzymatic strategies. Short chemical synthetic routes toward fluorinated racemic amines and prochiral ketones have been developed, which served as substrates to explore the suitability of lipases and transaminases in asymmetric biotransformations. The lipase-catalyzed kinetic resolution via acylation of racemic amines proceeded smoothly giving conversions close to 50% and excellent enantioselectivities. Alternatively, the biotransamination of the corresponding prochiral ketones was investigated giving access to both optically pure amine enantiomers using transaminases with complementary selectivity. High to quantitative conversion values were achieved, which allowed the isolation of the amines in moderate to high yields (40–88%). A deeper understanding of the latter process was enabled by performing theoretical calculations on thermodynamic and mechanistic aspects. Calculations showed that the biotransamination reactions are highly favoured by the presence of fluorine atoms and the pyridine ring.