Lipase-Catalyzed Chemoselective Ester Hydrolysis of Biomimetically Coupled Aryls for the Synthesis of Unsymmetric Biphenyl Esters

Abstract

Lipases are among the most frequently used biocatalysts in organic synthesis, allowing numerous environmentally friendly and inexpensive chemical transformations. Here, we present a biomimetic strategy based on iron(III)-catalyzed oxidative coupling and selective ester monohydrolysis using lipases for the synthesis of unsymmetric biphenyl-based esters under mild conditions. The diverse class of biphenyl esters is of pharmaceutical and technical relevance. We explored the potency of a series of nine different lipases of bacterial, fungal, and mammalian origin on their catalytic activities to cleave biphenyl esters, and optimized the reaction conditions, in terms of reaction time, temperature, pH, organic solvent, and water–organic solvent ratios, to improve the chemoselectivity, and hence control the ratio of unsymmetric versus symmetric products. Elevated temperature and increased DMSO content led to an almost exclusive monohydrolysis by the four lipases Candida rugosa lipase (CRL), Mucor miehei lipase (MML), Rhizopus niveus lipase (RNL), and Pseudomonas fluorescens lipase (PFL). The study was complemented by in silico binding predictions to rationalize the observed differences in efficacies of the lipases to convert biphenyl esters. The optimized reaction conditions were transferred to the preparative scale with high yields, underlining the potential of the presented biomimetic approach as an alternative strategy to the commonly used transition metal-based strategies for the synthesis of diverse biphenyl esters.

Cutinase ACut2 from Blastobotrysraffinosifermentans for the Selective Desymmetrization of the Symmetric Diester Diethyl Adipate to the Monoester Monoethyl Adipate

“…Compared to the chemical synthesis, lower temperatures and alcohol concentrations have to be used. Some lipases and pig liver esterase have already been successfully used for the monohydrolysis of various diesters [24][25][26][27][28][29][30]. Under the conditions tested, high monoester yields of 96 to 99+% were obtained [24,26,27].…”

“…Some lipases and pig liver esterase have already been successfully used for the monohydrolysis of various diesters [ 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. Under the conditions tested, high monoester yields of 96 to 99+% were obtained [ 24 , 26 , 27 ].…”

“…It is no foregone conclusion that lipases/esterases carry out chemoselective hydrolysis of only one of the two ester functions of the diester compound. CALB was not chemoselective at all, despite various adaptations of the reaction conditions [ 28 ]. Bianchi et al [ 31 ] used two lipases for the hydrolysis of terephthalic acid diesters, gaining only 60% monoester and 40% diacid.…”

“…In some cases, optimizing the reaction conditions can overcome the selectivity problems. Along these lines, Ehlert and coworkers [ 28 ] improved the chemoselectivity for four lipases until no diacid was detectable by adjusting the reaction time, temperature, and organic solvent concentration. The conversion, however, was low (max.…”

Lipase of Pachira speciosa seeds immobilized in chitosan beads: a recyclable bio-catalytic system

“…Las lipasas (E.C. 3.1.1.3) son enzimas altamente versátiles muy utilizadas en procesos biotecnológicos como la producción de detergentes, surfactantes, biopolímeros, aromatizantes, cosméticos (Patel et al, 2019;Chandra et al, 2020) y fármacos quirales (Ehlert et al, 2019); también, en la bioconversión de alimentos (Akshita et al, 2020) y en la síntesis de biocombustibles (Lv et al, 2021). Después de las proteasas, las lipasas son las enzimas más utilizadas en la industria, por lo que hay un gran interés en la búsqueda de nuevas fuentes que satisfagan las necesidades de un mercado en crecimiento (Fatima et al, 2020).…”