Reductive dehalogenation of β-haloacrylic ester derivatives mediated by ene-reductases

Chemoenzymatic Asymmetric Synthesis of Pregabalin Precursors via Asymmetric Bioreduction of β-Cyanoacrylate Esters Using Ene-Reductases

“…In addition, the size of the alcohol moiety of the (activating) ester group was varied in order to test its influence on the substrate-docking mode of substrates 5a – 7a within the active site. 4,6,18 All substrates were tested using a set of native ene-reductases, which have shown to possess a broad substrate spectrum on acrylic ester derivatives 5,6,15,18,19 (Scheme 1, Table 1). …”

Ene‐reductases and their Applications

“…However, the addition of a second activating group can increase the C═C bond polarization and facilitate the hydrogenation. Several studies have been performed on α,β-unsaturated dicarboxylic acids and esters [41,42] and α-halo-substituted unsaturated acids and esters [19,40,[43][44][45] for determining the reaction rate and/or stereochemical outcome of the asymmetric hydrogenation using ERs. For example, an additional halogenated substituent in the α-position was shown to be beneficial for ER activity, whereas β-alkyl or β-aryl substituents were detrimental for the reactivity of nonhalogenated substrates [40,43].…”

“…Two or more chlorine substituents caused a secondary spontaneous β-elimination reaction of hydrohalous acids after reduction of the alkene function, giving rise to sequential biodegradation hence generating the saturated carboxylic esters. This allowed for the production of both enantiomers of methyl 2-chloro-iodopropionate, 2-bromoiodopropionate, and 2-iodopropionate in good to excellent enantiopurity via enzyme-based stereocontrol using OYEs ( Figure 18.3a) [45]. Enantiopure α-haloesters are, in particular, valuable synthons for the synthesis of chiral active pharmaceutical ingredients used for the treatment of noninsulindependent type-2 diabetes mellitus (T2DM) [22].…”

Old Yellow Enzyme-Catalysed Asymmetric Hydrogenation: Linking Family Roots with Improved Catalysis

“…Catalysts 2017, 7, 130 2 of 24 activated alkenes with an electron withdrawing group (EWG) such as aldehyde, ketone, anhydride [8,10,11], nitro [9,12,13], (di)ester [8,[14][15][16][17], (di)carboxylic acid [18][19][20], cyclic imide [21][22][23], nitrile [24], β-cyanoacrylate [25], β-nitroacrylate [26], and several other functional groups [27]. There are many examples of the high industrial potential of OYEs for the synthesis of valuable target products [28][29][30][31].…”