3 publications

3 publications

Covalent Anchoring of a Racemization Catalyst to CALB-Beads: Towards Dual Immobilization of DKR Catalysts

Klein Gebbink, R.J.M.; van Koten, G.

Tetrahedron Lett. 2011, 52, 1601-1604, 10.1016/j.tetlet.2011.01.106

The preparation of a heterogeneous bifunctional catalytic system, combining the catalytic properties of an organometallic catalyst (racemization) with those of an enzyme (enantioselective acylation) is described. A novel ruthenium phosphonate inhibitor was synthesized and covalently anchored to a lipase immobilized on a solid support (CALB, Novozym® 435). The immobilized bifunctional catalytic system showed activity in both racemization of (S)-1-phenylethanol and selective acylation of 1-phenylethanol.


Metal: Ru
Anchoring strategy: Covalent
Optimization: Chemical
Reaction: Acylation
Max TON: ---
ee: >99%
PDB: ---
Notes: Lipase CALB is immobilized on a solid support (Novozym®435). Dynamic kinetic resolution (DKR) of 1-phenylethanol to the acylated product.

Lipase Active Site Covalent Anchoring of Rh(NHC) Catalysts: Towards Chemoselective Artificial Metalloenzymes

Klein Gebbink, R.J.M.

Chem. Commun. 2015, 51, 6792-6795, 10.1039/c4cc09700a

A Rh(NHC) phosphonate complex reacts with the lipases cutinase and Candida antarctica lipase B resulting in the first (soluble) artificial metalloenzymes formed by covalent active site-directed hybridization. When compared to unsupported complexes, these new robust hybrids show enhanced chemoselectivity in the (competitive) hydrogenation of olefins over ketones.


Metal: Rh
Ligand type: Carbene
Host protein: Cutinase
Anchoring strategy: Covalent
Optimization: ---
Reaction: Hydrogenation
Max TON: 20
ee: rac.
PDB: 1CEX
Notes: ---

Metal: Rh
Ligand type: Carbene
Anchoring strategy: Covalent
Optimization: ---
Reaction: Hydrogenation
Max TON: 20
ee: rac.
PDB: 4K6G
Notes: ---

Preparation of an Immobilized Lipase-Palladium Artificial Metalloenzyme as Catalyst in the Heck Reaction: Role of the Solid Phase

Filice, M.; Palomo, J.M.

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: Pd
Anchoring strategy: Covalent
Optimization: Chemical & genetic
Max TON: ~4160
ee: 96
PDB: ---
Notes: ArM is immobilized on Sepabeads.