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Exploiting the Biocatalytic Toolbox for the Asymmetric Synthesis of the Heart‐Rate Reducing Agent Ivabradine
Author(s) -
PedragosaMoreau Sandrine,
Le Flohic Alexandre,
Thienpondt Vivien,
Lefoulon François,
Petit AnneMarie,
RíosLombardía Nicolás,
Morís Francisco,
GonzálezSabín Javier
Publication year - 2017
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.201601222
Subject(s) - enantiopure drug , kinetic resolution , ivabradine , chemistry , amine gas treating , aldehyde , enantioselective synthesis , yield (engineering) , combinatorial chemistry , organic chemistry , catalysis , heart rate , medicine , materials science , blood pressure , metallurgy , radiology
Several chemoenzymatic routes have been evaluated for the production of the heart‐rate reducing agent ivabradine. Lipases and ω‐transaminases have been identified as useful biocatalysts for the preparation of key enantiopure precursors. The lipase‐catalysed kinetic resolution by alkoxycarbonylation of a racemic primary amine and subsequent chemical reduction of the resulting carbamate provided an N ‐methylated ( S )‐amine, one step away from ivabradine. Alternatively, the dynamic kinetic resolution by asymmetric bioamination of an aldehyde precursor enabled, in a four‐step sequence, the preparative scale synthesis of enantiopure ivabradine in 50% overall yield.