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Enzymatic Synthesis of Optically Active Lactones via Asymmetric Bioreduction using Ene‐Reductases from the Old Yellow Enzyme Family
Author(s) -
Turrini Nikolaus G.,
Hall Mélanie,
Faber Kurt
Publication year - 2015
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.201500094
Subject(s) - chemistry , racemization , kinetic resolution , yield (engineering) , ene reaction , enantiomer , substrate (aquarium) , biocatalysis , enzyme , stereochemistry , enantiomeric excess , lactone , enantioselective synthesis , resolution (logic) , catalysis , organic chemistry , reaction mechanism , materials science , oceanography , artificial intelligence , geology , computer science , metallurgy
In contrast to the widely studied asymmetric bioreduction of α,β‐unsaturated carboxylic acid esters catalyzed by ene‐reductases, the reaction applied to lactones remains unexplored. A broad set of ene‐reductases was found to reduce various α‐, β‐ and γ‐substituted α,β‐unsaturated butyrolactones to yield the corresponding saturated non‐racemic lactones. Substitution patterns greatly influenced activities and stereoselectivities and lactone products were obtained in moderate to excellent yields; importantly, enzyme‐based stereocontrol allowed access to both enantiomers in up to >99% ee . Chiral recognition of a distant γ‐center led to kinetic resolution with remarkable enantioselectivities (E values up to 49). An unprecedented case of dynamic kinetic resolution was observed with 3‐methyl‐5‐phenylfuran‐2(5 H )‐one, whereby spontaneous racemization of the substrate furnished the product in up to 73% conversion and >99% ee and 96% de .