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Synthesis of D ‐ and L ‐Phenylalanine Derivatives by Phenylalanine Ammonia Lyases: A Multienzymatic Cascade Process
Author(s) -
Parmeggiani Fabio,
Lovelock Sarah L.,
Weise Nicholas J.,
Ahmed Syed T.,
Turner Nicholas J.
Publication year - 2015
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201410670
Subject(s) - phenylalanine , chemistry , phenylalanine ammonia lyase , ammonia , biochemistry , amino acid
The synthesis of substituted D ‐phenylalanines in high yield and excellent optical purity, starting from inexpensive cinnamic acids, has been achieved with a novel one‐pot approach by coupling phenylalanine ammonia lyase (PAL) amination with a chemoenzymatic deracemization (based on stereoselective oxidation and nonselective reduction). A simple high‐throughput solid‐phase screening method has also been developed to identify PALs with higher rates of formation of non‐natural D ‐phenylalanines. The best variants were exploited in the chemoenzymatic cascade, thus increasing the yield and ee value of the D ‐configured product. Furthermore, the system was extended to the preparation of those L ‐phenylalanines which are obtained with a low ee value using PAL amination.