Combining regio‐ and enantioselectivity of lipases for the preparation of (R)‐4‐chloro‐2‐butanol

Abstract

Preparation of 98% ee (R)-4-chloro-2-butanol was carried out by the enzymatic hydrolysis of chlorohydrin esters, using fungal resting cells and commercial enzymes. Hydrolyzes were carried out using lipases from Candida antarctica (Novozym 435), C. rugosa, Rhizomucor miehei (Lipozyme IM), Burkolia cepacia, and resting cells of Rhizopus oryzae and Aspergillus flavus. The influence of the enzyme, the solvent, the temperature, and the alkyl chain length on the selectivity of hydrolyzes of isomeric mixtures of chlorohydrin esters is described. Regioselectivity was higher than 95% for some of the tested lipases. Novozym 435 allowed preparation of the (R)-4-chloro-2-butanol after 15 min of reaction at 30-40 degrees C.

Immobilization and stability of a Rhizopus oryzae lipase expressed in Pichia pastoris: Comparison between native and recombinant variants

“…Lipases are widely used in industry, because they possess advantageous properties such as high specificity and selectivity. Well-known and diverse applications include pharmaceutical processing, [7][8][9][10] resolving racemic mixtures, [11][12][13][14][15] biosurfactant production, 16,17 biosensors construction, 18 and biodiesel synthesis. [19][20][21] Because of the utility of lipases in industrial application, they have been immobilized on a wide range of supports.…”

Utilization of deep‐sea microbial esterase PHE21 to generate chiral sec‐butyl acetate through kinetic resolutions

“…Previously, the reports about producing chiral sec‐butyl acetate and sec‐butyl alcohol through direct enzymatic hydrolysis of racemic sec‐butyl acetate or sec‐butyl alcohol, especially by esterases/lipases, were quite rare. Other experiments about preparation of chiral long‐chain secondary alcohol through direct enzymatic hydrolysis were reported . The structural differences on both sides of the chiral center in long‐chain secondary alcohols may greatly facilitate the kinetic resolution using esterases/lipases.…”

“…Other experiments about preparation of chiral long-chain secondary alcohol through direct enzymatic hydrolysis were reported. 14,17,18 The structural differences on both sides of the chiral center in long-chain secondary alcohols may greatly facilitate the kinetic resolution using esterases/ lipases. In our study, esterase PHE21 could efficiently catalyze the enzymatic kinetic resolutions of (±)-sec-butyl acetate with both high enantiomeric excess and yield, indicating that marine microbial esterase PHE21 was identified as a useful biocatalyst for asymmetric synthesis through hydrolysis reactions.…”

“…Esterases (EC 3.1.1.1) are 1 class of important hydrolyases widely used in both laundry industry and synthetic industry . Chiral secondary alcohols can be prepared by using esterases as the green biocatalysts through transesterifications, esterifications, or direct hydrolysis reactions . One great advantage of the kinetic resolutions catalyzed by esterases over the bioreductions catalyzed by dehydrogenases is that no expensive cofactors are required during biocatalysis, thus greatly reducing the production costs of chiral products.…”

“…[10][11][12] Chiral secondary alcohols can be prepared by using esterases as the green biocatalysts through transesterifications, esterifications, or direct hydrolysis reactions. [13][14][15][16] One great advantage of the kinetic resolutions catalyzed by esterases over the bioreductions catalyzed by dehydrogenases is that no expensive cofactors are required during biocatalysis, thus greatly reducing the production costs of chiral products. Chiral secondary butanol and its ester derivatives are crucial chiral chemicals and resolving agents and are in great demand in industry.…”