Preparation of an Immobilized Lipase-Palladium Artificial Metalloenzyme as Catalyst in the Heck Reaction: Role of the Solid Phase
Adv. Synth. Catal. 2015, 357, 2687-2696, 10.1002/adsc.201500014
A p‐nitrophenylphosphonate palladium pincer was synthesized and selectively inserted by irreversible attachment on the catalytic serine of different commercial lipases with good to excellent yields in most cases. Among all, lipase from Candida antarctica B (CAL‐B) was the best modified enzyme. The artificial metalloenzyme CAL‐B‐palladium (Pd) catalyst was subsequently immobilized on different supports and by different orienting strategies. The catalytic properties of the immobilized hybrid catalysts were then evaluated in two sets of Heck cross‐coupling reactions under different conditions. In the first reaction between iodobenzene and ethyl acrylate, the covalent immobilized CAL‐B‐Pd catalyst resulted to be the best one exhibiting quantitative production of the Heck product at 70 °C in dimethylformamide (DMF) with 25% water and particularly in pure DMF, where the soluble Pd pincer was completely inactive. A post‐immobilization engineering of catalyst surface by its hydrophobization enhanced the activity. The selectivity properties of the best hybrid catalyst were then assessed in the asymmetric Heck cross‐coupling reaction between iodobenzene and 2,3‐dihydrofuran retrieving excellent results in terms of stereo‐ and enantioselectivity.
Metal: PdLigand type: Thioether (Pincer complex)Host protein: Lipase B from C. antarctica (CALB)Optimization: Chemical & geneticReaction: Heck cross-couplingMax TON: ~4160ee: 96PDB: ---Notes: ArM is immobilized on Sepabeads.
Synthesis of a Heterogeneous Artificial Metallolipase with Chimeric Catalytic Activity
Chem. Commun. 2015, 51, 9324-9327, 10.1039/C5CC02450A
A solid-phase strategy using lipase as a biomolecular scaffold to produce a large amount of Cu2+-metalloenzyme is proposed here. The application of this protocol on different 3D cavities of the enzyme allows creating a heterogeneous artificial metallolipase showing chimeric catalytic activity. The artificial catalyst was assessed in Diels–Alder cycloaddition reactions and cascade reactions showing excellent catalytic properties.
Metal: CuLigand type: PhenanthrolineHost protein: Lipase from G. thermocatenulatus (GTL)Optimization: GeneticReaction: Diels-Alder cycloadditionMax TON: 411ee: 92PDB: ---Notes: ArM is immobilized on Sepabeads. Endo/exo = 93.5%
Metal: CuLigand type: PhenanthrolineHost protein: Lipase from G. thermocatenulatus (GTL)Optimization: GeneticReaction: ReductionMax TON: ---ee: ---PDB: ---Notes: Cascade reaction: Ester hydrolysis (natural function of the host protein) followed by reduction (function of the designed ArM).