Biocatalytic reduction of α,β-unsaturated carboxylic acids to allylic alcohols
We have developed robust in vivo and in vitro biocatalytic systems that enable reduction of α,β-unsaturated carboxylic acids to allylic alcohols and their saturated analogues. These compounds are prevalent scaffolds in many industrial chemicals and pharmaceuticals. A substrate profiling study of a c...
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Veröffentlicht in: | Green chemistry : an international journal and green chemistry resource : GC 2020-06, Vol.22 (12), p.3927-3939 |
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Zusammenfassung: | We have developed robust
in vivo
and
in vitro
biocatalytic systems that enable reduction of α,β-unsaturated carboxylic acids to allylic alcohols and their saturated analogues. These compounds are prevalent scaffolds in many industrial chemicals and pharmaceuticals. A substrate profiling study of a carboxylic acid reductase (CAR) investigating unexplored substrate space, such as benzo-fused (hetero)aromatic carboxylic acids and α,β-unsaturated carboxylic acids, revealed broad substrate tolerance and provided information on the reactivity patterns of these substrates.
E. coli
cells expressing a heterologous CAR were employed as a multi-step hydrogenation catalyst to convert a variety of α,β-unsaturated carboxylic acids to the corresponding saturated primary alcohols, affording up to >99% conversion. This was supported by the broad substrate scope of
E. coli
endogenous alcohol dehydrogenase (ADH), as well as the unexpected C&z.dbd;C bond reducing activity of
E. coli
cells. In addition, a broad range of benzofused (hetero)aromatic carboxylic acids were converted to the corresponding primary alcohols by the recombinant
E. coli
cells. An alternative one-pot
in vitro
two-enzyme system, consisting of CAR and glucose dehydrogenase (GDH), demonstrates promiscuous carbonyl reductase activity of GDH towards a wide range of unsaturated aldehydes. Hence, coupling CAR with a GDH-driven NADP(H) recycling system provides access to a variety of (hetero)aromatic primary alcohols and allylic alcohols from the parent carboxylates, in up to >99% conversion. To demonstrate the applicability of these systems in preparative synthesis, we performed 100 mg scale biotransformations for the preparation of indole-3-aldehyde and 3-(naphthalen-1-yl)propan-1-ol using the whole-cell system, and cinnamyl alcohol using the
in vitro
system, affording up to 85% isolated yield.
Robust
in vitro
and
in vivo
carboxylic acid reductase (CAR)-based biocatalytic systems have been developed that enable hydrogenation of α,β-unsaturated carboxylic acids to allylic alcohols and their saturated analogues. |
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ISSN: | 1463-9262 1463-9270 |
DOI: | 10.1039/d0gc00867b |