RESUMEN
Enzyme-containing ionic liquids (ILs) were immobilized in cellulose-2.5-acetate microbeads particles embedded in a porous monolithic polyurethane matrix. This bioreactor was used under continuous liquid-liquid conditions by dissolving the substrates in a nonpolar organic phase immiscible with the ILs, thereby creating a biphasic system. Lipases (candida antarctica lipaseâ B, CALB, candida rugosa lipase, CRL) were used to catalyze the enantioselective transesterification of racemic (R,S)-1-phenylethanol with vinyl butyrate and vinyl acetate, the esterification of (+/-)-2-isopropyl-5-methylcyclohexanol with propionic anhydride and the amidation of (R,S)-1-phenylethylamine with ethyl methoxyacetate. With this unique setup, very high productivities, that is, turnover numbers (TONs) up to 5.1×106 and space-time yields (STYs) up to 28â g product L-1 h-1 , exceeding the corresponding values for batch-type reactions by a factor of 3100 and 40, respectively, were achieved while maintaining or even enhancing enantioselectivity compared to batch reactions via kinetic resolution. To our best knowledge, this is the first continuously operated bioreactor using supported liquid-liquid conditions that shows these features in the synthesis of chiral esters and amides.
Asunto(s)
Reactores Biológicos , Lipasa/metabolismo , Anhídridos/química , Catálisis , Ciclohexanonas/química , Esterificación , Fenetilaminas/química , Propionatos/química , EstereoisomerismoRESUMEN
Mesoporous monolithic hybrid cellulose-2.5-acetate (CA)/polymer supports were prepared under solvent-induced phase separation conditions using cellulose-2.5-acetate microbeads 8-14â µm in diameter, 1,1,1-tris(hydroxymethyl)propane and 4,4'-methylenebis(phenylisocyanate) as monomers as well as THF and n-heptane as porogenic solvents. 4-(Dimethylamino)pyridine and dibutyltin dilaurate (DBTDL), respectively, were used as catalysts. Monolithic hybrid supports were used in transesterification reactions of vinyl butyrate with 1-butanol under continuous, supported ionic liquid-liquid conditions with Candida antarctica lipaseâ B (CALB) and octylmethylimidazolium tetrafluoroborate ([OMIM(+) ][BF4 (-) ]) immobilized within the CA beads inside the polymeric monolithic framework and methyl tert-butyl ether (MTBE) as the continuous phase. The new hybrid bioreactors were successfully used in dimensions up to 2×30â cm (V=94â mL). Under continuous biphasic liquid-liquid conditions a constant conversion up to 96 % was achieved over a period of 18â days, resulting in a productivity of 58â µmol mg(-1) (CALB)â min(-1) . This translates into an unprecedented turnover number (TON) of 3.9×10(7) within two weeks, which is much higher than the one obtained under standard biphasic conditions using [OMIM(+) ][BF4 (-) ]/MTBE (TON=2.7×10(6) ). The continuous liquid-liquid setup based on a hybrid reactor presented here is strongly believed to be applicable to many other enzyme-catalyzed reactions.