Lipase Immobilized on MCFs as Biocatalysts for Kinetic and Dynamic Kinetic Resolution of sec-Alcohols

Abstract

Dynamic kinetic resolution (DKR) is one of the most attractive methods for enantioselective synthesis. In the reported studies, lipase B from Candida antarctica (CALB) immobilized on siliceous mesoporous cellular foams (MCF) functionalized with different hydrophobic groups, and two ruthenium complexes with substituted cyclopentadienyl ligands were investigated as catalysts for the chemoenzymatic DKR of (rac)-1-phenylethanol, using Novozym 435 as a benchmark biocatalyst. Studies on the (rac)-1-phenylethanol transesterification reaction showed that CALB supported on MCFs grafted with methyl groups is a promising biocatalyst and isopropenyl acetate is a preferable acylation agent. Both Ru-complexes activated by K3PO4 or t-BuOK, proved to be effective catalysts of the racemization reaction. The final DKR experiments using all catalysts combinations singled out, gave 96% conversion, and (R)-1-phenylethyl acetate enantiomeric excess of 98% in 8 h using K3PO4 activator.

Microbial Lipases and Their Potential in the Production of Pharmaceutical Building Blocks

“…When lipases such as CAL B (free or immobilized) have been used in DKR, they require an auxiliary catalyst with racemization activity against the substrate to be used. These usually require the use of an inert atmosphere in the case of a catalyst based on precious metals complexes [ 226 ]. This makes it harder to establish simplified and less expensive reaction systems required in the industry.…”

Asymmetric Synthesis of the Cyclohexyl Fragment in RORγt Inhibitor (BMS-986251) Enabled by a Dynamic Kinetic Resolution of Hageman’s Ester

“…To circumvent the issues posed by the low yield of the kinetic resolution, and its impact on material throughput, we became interested in considering alternatives which could result in a DKR process. To this end, the expected high acidity of the proton in the allylic position in the ring of 2 suggested that an enzyme-catalyzed hydrolysis of this substrate could be adequate to enable such DKR under the right experimental conditions. Gratifyingly, a screening of commercially available lipases identified Lipozyme CAL-B as an extremely effective catalyst.…”

Kinetic and Dynamic Kinetic Resolution by Dual Catalysis

“…The same group also reported a base‐free DKR protocol using the combined action of a ruthenium‐lipase dual catalytic system for the resolution of secondary alcohols (Table 8). [45] In a subsequent study, Szymanska's group reported DKR of rac ‐1‐phenylethanol by employing a cyclopentadienyl substituted ruthenium complex for racemization in combination with CaLB immobilized on siliceous MCFs (mesoporous cellular foams) with excellent ee in the presence of K 3 PO 4 activator [46] …”

“…[45] In a subsequent study, Szymanska's group reported DKR of rac-1-phenylethanol by employing a cyclopentadienyl substituted ruthenium complex for racemization in combination with CaLB immobilized on siliceous MCFs (mesoporous cellular foams) with excellent ee in the presence of K 3 PO 4 activator. [46] More recently, Xu and coworkers reported the DKR of rac-1phenethylamine by employing metal nanocatalyst and enzyme lipase (Table 9). [47] The Pd-loaded core-shell MOF racemization catalyst (HM-MIL@Pd@ZIF-8) was prepared in 3 steps and combined with Novozym-435.…”