BioChem - DOS

Exploiting the Biocatalytic Toolbox for the Asymmetric Synthesis of the Heart-Rate Reducing Agent Ivabradine

Advanced synthesis & catalysis

Pedragosa‐ Moreau, Sandrine; Le Flohic, Alexandre; Thienpondt, Vivien; Lefoulon, Franç ois; Petit, Anne‐ Marie; Rí os‐ Lombardí a, Nicolá s; Morí s, Francisco; Gonzá lez‐ Sabí n, Javier

<P><B>Abstract</B></P><P>Several chemoenzymatic routes have been evaluated for the production of the heart&#8208;rate reducing agent ivabradine. Lipases and &omega;&#8208;transaminases have been identified as useful biocatalysts for the preparation of key enantiopure precursors. The lipase&#8208;catalysed kinetic resolution by alkoxycarbonylation of a racemic primary amine and subsequent chemical reduction of the resulting carbamate provided an <I>N</I>&#8208;methylated (<I>S</I>)&#8208;amine, one step away from ivabradine. Alternatively, the dynamic kinetic resolution by asymmetric bioamination of an aldehyde precursor enabled, in a four&#8208;step sequence, the preparative scale synthesis of enantiopure ivabradine in 50% overall yield.</P>

2017

1615-4150

1615-4169

359

3

pp.485-493

10.1002/adsc.201601222

http://click.ndsl.kr/servlet/OpenAPIDetailView?keyValue=05787966&target=NART&cn=NART77301722

amines; asymmetric synthesis; biotransformations; lipases; transaminases