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Preparative Asymmetric Synthesis of Canonical and Non‐canonical α‐amino Acids Through Formal Enantioselective Biocatalytic Amination of Carboxylic Acids
Author(s) -
Dennig Alexander,
Blaschke Fabio,
Gandomkar Somayyeh,
Tassano Erika,
Nidetzky Bernd
Publication year - 2019
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.201801377
Subject(s) - enantiopure drug , chemistry , amino acid , enantioselective synthesis , stereochemistry , combinatorial chemistry , organic chemistry , catalysis , biochemistry
Chemical and biocatalytic synthesis of non‐canonical α‐amino acids (ncAAs) from renewable feedstocks and using mild reaction conditions has not efficiently been solved. Here, we show the development of a three‐step, scalable and modular one‐pot biocascade for linear conversion of renewable fatty acids (FAs) into enantiopure l ‐α‐amino acids. In module 1, selective α‐hydroxylation of FAs is catalyzed by the P450 peroxygenase P450 CLA . By using an automated H 2 O 2 supplementation system, efficient conversion (46 to >99%; TTN>3300) of a broad range of FAs (C6:0 to C16:0) into valuable α‐hydroxy acids (α‐HAs; >90% α‐selective) is shown on preparative scale (up to 2.3 g L −1 isolated product). In module 2, a redox‐neutral hydrogen borrowing cascade (alcohol dehydrogenase/amino acid dehydrogenase) allowed further conversion of α‐HAs into l ‐α‐AAs (20 to 99%). Enantiopure l ‐α‐AAs (e.e. >99%) including the pharma synthon l ‐homo‐phenylalanine can be obtained at product titers of up to 2.5 g L −1 . Based on renewables and excellent atom economy, this biocascade is among the shortest and greenest synthetic routes to structurally diverse and industrially relevant ncAAs.