BioChem - DOS

Biocompatible metal-assisted C-C cross-coupling combined with biocatalytic chiral reductions in a concurrent tandem cascade

Chemical communications : Chem comm

Schaaf, Patricia; Bayer, Thomas; Koley, Moumita; Schnü rch, Michael; Bornscheuer, Uwe T.; Rudroff, Florian; Mihovilovic, Marko D.

<P>In this study, we present a concurrent chemo/biocatalytic one pot reaction cascade by combining a metal (Pd/Cu) assisted Liebeskind-Srogl (L-S) coupling with an enantioselective enzymatic reduction for the production of chiral amines and alcohols. The latter transformation was realized by applying enantiocomplementary alcohol dehydrogenases from <I>Lactobacillus kefir</I> (<I>R</I>-selective) and <I>Rhodococcus ruber</I> (<I>S</I>-selective). Compatibility issues were solved by investigating first the L-S-coupling protocol in water at room temperature. Subsequently, we investigated two different biphasic systems and applied a biomimicking approach to separate enzyme-deactivating components. By using a lipophilic membrane in a smart reactor design, we were able to perform concurrent catalytic cascades with overall concentrations up to 100 mM substrate and to produce 1-phenylethylamine and several chiral alcohols in high yields (up to 81% over 2 steps) and enantiomeric purity ((+) and (&#x2212;)-enantiomers both with 99% ee).</P><P>Graphic Abstract</P><P>We present a concurrent chemo/biocatalytic one pot reaction cascade by combining a metal (Pd/Cu) assisted Liebeskind-Srogl coupling with an enantioselective enzymatic reduction for the production of chiral amines and alcohols.<BR/><IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c8cc05304a'/><BR/></P>

2018

The Royal Society of Chemistry

1359-7345

1364-548x

54

92

pp.12978-12981

10.1039/c8cc05304a

http://click.ndsl.kr/servlet/OpenAPIDetailView?keyValue=05787966&target=NART&cn=NART94905813