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Asymmetric Biocatalytic Synthesis of Fluorinated Pyridines through Transesterification or Transamination: Computational Insights into the Reactivity of Transaminases
Author(s) -
LópezIglesias María,
GonzálezMartínez Daniel,
RodríguezMata María,
Gotor Vicente,
Busto Eduardo,
Kroutil Wolfgang,
GotorFernández Vicente
Publication year - 2017
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201600835
Subject(s) - chemistry , kinetic resolution , transamination , pyridine , substituent , stereoselectivity , enantiomeric excess , organic chemistry , acylation , selectivity , enantiomer , reactivity (psychology) , ring (chemistry) , transesterification , enantioselective synthesis , lipase , amine gas treating , biocatalysis , isopropylamine , catalysis , enzyme , reaction mechanism , medicine , alternative medicine , pathology
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.