Helmut Hönig

Chemo-enzymatic synthesis of all isomeric 3-phenylserines and -isoserines

Abstract The synthesis of all isomers of 3-phenylserines and 3-phenylisoserines in enantiomerically pure form is presented. Diastereomerically pure educts (threo/erythro-2-azido-3-butanoyoxy-3-phenyl-propionic esters, threo/erythro-3-azido-2-butanoyloxy-3-phenylpropionic esters, threo-2-butanoylamino-3-butanoyloxy-3-phenylpropionic ester, erythro-3-butanoylamino-2-butanoyloxy-3-phenyl-propionamide) were prepared from cinnamic acid derivatives or via aldol condensations of benzaldehyde and suitable enolates in few steps. These racemates were resolved with lipases from Candida cylindracea (CC) and Pseudomonas fluorescens (P) and the obtained products were hydrogenated to 3-phenylserines and -isoserines. The influence of the acyl group in the enzymatic resolution of erythro-3-azido-2-acyloxy-3-phenylpropionic esters was investigated.

Enantioselective synthesis of ethyl nipecotinate using cinchona modified heterogeneous catalysts

Ethyl nicotinate was hydrogenated to ethyl nipecotinate in two steps. In the first step, the starting material was converted to the 1,4,5,6-tetrahydro derivative with PdrC and hydrogen in 76% yield. The hydrogenation of this intermediate was investigated with both unmodified and 10,11-dihydrocinchonidine modified noble metal catalysts and the influence of the catalyst metal, support, solvent and modifier concentration was tested. Catalyst activity was low in all cases, probably because the C5C double bond is part of a vinylogeous carbamate. The highest activity was observed with Rh and RhrPt .

Selectivity of lipases: Conformational analysis of suggested intermediates in ester hydrolysis of chiral primary and secondary alcohols

Abstract Conformational analysis of the proposed tetrahedral transition state of different model esters in the active sites of the lipases of Candida rugosa and Pseudomonas cepacia are used to analyze structural reasons for the unique enantiomeric preference of lipases towards the cleavage of esters of chiral primary and secondary alcohols. The results are compared with the existing rules for the preference of one specific enantiomer in the hydrolysis of esters of chiral alcohols. Interesting results on the dynamics behaviour of some enantiomers within the lipases are reported.

A novel and efficient synthesis of (+)- and (−)-trans-2-aminocyclohexanol by enzymatic hydrolysis

Abstract Both enantiomers of trans-2-aminocyclohexanol were obtained by enzymatic hydrolysis of (±)-2-azidocyclohexanoates using lipases and subsequent hydrogenation.

ENZYMATIC RESOLUTIONS OF HETEROCYCLIC ALCOHOLS

The butyrates and acetates of heterocyclic alcohols like 3 - hydroxy tetrahydrofuran and - pyran, 3- and 4 - chromanol as well as the corresponding sulfur heterocycles were hydrolyzed using lipase from Candida rugosa (CRL) and from Pseudomonas cepacia, (PCL). Poor to excellent enantioselectivities were obtained depending on the structure of the substrates. An electrostatic amendment to the steric substrate model for PGL is proposed.

A facile synthesis of 1,2,-o-isopropylidene-β-L-idofuranurono-6,3-lactone

Abstract A simple, high yield, two step synthesis of 1,2,-O-isopropylidene-β-L-idofuranurono-6,3-lactone is described.

Stabilitätsuntersuchungen an Bor-Stickstoff-Sauerstoff-Heterocyclen mittels11B-NMR-Spektroskopie

Boron-11-NMR-spectroscopy is proven to be a powerful tool for the estimation of hydrolytic stabilities of dioxazabora-heterocycles and their corresponding N-Mannich-bases with different carboxamides. In addition this method is used for predicting complex molecular structures of boron-compounds otherwise impossible to elucidate. Several new compounds and11B-NMR-data are described.

Enzymatic resolutions of cyclic amino alcohol precursors

Racemic butyrates of trans-2-azido as well as trans-2-nitro and trans-2-cyano cycloalkanols were hydrolysed to the corresponding optically active alcohols with the aid of lipases from Candida cylindracea and Pseudomonas sp. respectively. These precursors of amino alcohols could be produced in optical yields ranging from 85 to > 98% e.e. Differences in the catalytic behaviour of the two enzymes depending on ring sizes were observed.

How large are the active sites of the lipases from candida rugosa and from pseudomonas cepacia

Abstract Racemates of 2-Azido alcohols of large, polycyclic systems can be resolved by enzyme catalyzed hydrolysis of the respective butyrates using lipases from Candida rugosa ( cylindracea ) and from Pseudomonas cepacia ( fluorescens ) with excellent optical and chemical yields. An estimate of the size of the respective hydrophobic pockets of these lipases is given.

On the Prediction of the Enantioselectivity of Candida rugosa Lipase by Comparative Molecular Field Analysis

Comparative molecular field analysis (CoMFA) was used to derive a quantitative substrate model for the enzymatic resolution of norbornanol esters by the lipase of Candida rugosa. Within these calculations, the steric and electrostatic interactions of both enantiomers and the differences in the corresponding two fields were used for the correlation of the substrate structure with the enantioselectivity of the hydrolysis. Different alignments of the molecules were used to improve the model.