Ute Hoch

Biotransformations with Peroxidases

Enzymes are chiral catalysts and are able to produce optically active molecules from prochiral or racemic substrates by catalytic asymmetric induction. One of the major challenges in organic synthesis is the development of environmentally acceptable chemical processes for the preparation of enantiomerically pure compounds, which are of increasing importance as pharmaceuticals and agrochemicals. Enzymes meet this challenge! For example, a variety of peroxidases effectively catalyze numerous selective oxidations of electron-rich substrates, which include the hydroxylation of arenes, the oxyfunctionalizations of phenols and aromatic amines, the epoxidation and halogenation of olefins, the oxygenation of heteroatoms and the enantioselective reduction of racemic hydroperoxides. In this review, we summarize the important advances achieved in the last few years on peroxidase-catalyzed transformations, with major emphasis on preparative applications.

Kinetic resolution of chiral α-hydroperoxy esters by horseradish peroxidase-catalyzed enantioselective reduction to α-hydroxy esters

Abstract The kinetic resolution of the methyl α-hydroperoxy esters 4 has been investigated by horseradish peroxidase (HRP)-catalyzed reduction to the corresponding optically active α-hydroxy ester 5 in the presence of guaiacol. The method allows for the first time the preparation of enantiomerically pure ( ee > 97%) methyl ( R )-2-hydroperoxybutyrate ( 4a ). The HRP enzyme is sensitive to the steric demand of the ester alkyl side chain, as manifested by ethyl ( ee > 97%) and isopropyl ( ee 79%), while the tert -butyl derivative is not accepted by the enzyme (no reduction).

Enzyme-catalyzed kinetic resolution of racemic secondary hydroperoxides

Abstract The kinetic resolution of 1,2,3,4-tetrahydro[1]naphthyl and other secondary and tertiary hydroperoxides has been investigated by acylation with isopropenyl acetate in the presence of various lipases, by chloroperoxidase-catalyzed asymmetric oxidation of sulfides, and by horseradish peroxidase (HRP)-catalyzed reduction in the presence of guaiacol. For preparative purposes, the latter method is the best one and allows for the first time the isolation and characterization of the enantiomerically pure ( S )-1,2,3,4-tetrahydro[1]naphthyl hydroperoxide. Tertiary hydroperoxides are not accepted as substrates by HRP.

Horseradish peroxidase - a biocatalyst for the one-pot synthesis of enantiomerically pure hydroperoxides and alcohols

The kinetic resolution of racemic hydroperoxides by horseradish peroxidase (HRP)-catalyzed reduction was investigated, with major emphasis on catalytic efficiency and enantioselectivity. The kinetic parameters of the enzymatic reaction were determined, enantiomeric excess (ee) and absolute configurations of hydroperoxides and alcohols were measured, and a broad spectrum of structurally different hydroperoxides were investigated to assess the scope and limitation of this method. Both the catalytic efficiency and the stereoselectivity of HRP highly depend on the structure of the hydroperoxides. The enzyme selectively recognizes sterically unencumbered hydroperoxides, which allows kinetic resolution by means of enantioselective reduction to yield optically active hydroperoxides and alcohols in excellent ee values (up to 99%). Functional groups in the hydroperoxide molecule do not affect the stereoselectivity of the enzyme, which permits a large number of functionalized hydroperoxides to be resolved by HRP.

Horseradish peroxidase (HRP)-catalysed enantioselective reduction of racemic hydroperoxy homoallylic alcohols: a novel enzymatic method for the preparation of optically active, unsaturated diols and hydroperoxy alcohols

The kinetic resolution of chiral diastereomeric hydroperoxy homoallylic alcohols 1 by horseradish peroxidase-catalyzed asymmetric reduction affords the optically active (R,R) or (R,S) allylic diols 2 and (S,S) or (S,R) hydroperoxy homoallylic alcohols 1 in high enantiomeric excess (up to 99%).