- Exploiting the Biocatalytic Toolbox for the Asymmetric Synthesis of the Heart-Rate Reducing Agent Ivabradine
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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. (Figure presented.).
- Pedragosa-Moreau, Sandrine,Le Flohic, Alexandre,Thienpondt, Vivien,Lefoulon, Fran?ois,Petit, Anne-Marie,Ríos-Lombardía, Nicolás,Morís, Francisco,González-Sabín, Javier
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supporting information
p. 485 - 493
(2017/02/10)
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- Process for the synthesis of 1,3,4,5-tetrahydro-2H-3-benzazepin-2-one compounds. and application in the synthesis of ivabradine and addition salts thereof with a pharmaceutically acceptable acid
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Process for the synthesis of compounds of formula (I): wherein R1 and R2, which may be the same or different, each represent a linear or branched (C1-C8)alkoxy group or form, together with the carbon atom carrying them, a 1,3-dioxane, 1,3-dioxolane or 1,3-dioxepane ring. Application in the synthesis of ivabradine, addition salts thereof with a pharmaceutically acceptable acid, and hydrates thereof.
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Page/Page column 2
(2008/06/13)
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