Markus Juza - Academia.edu (original) (raw)

Papers by Markus Juza

Trends in Biotechnology, 2000

The increased awareness of the differences in biological activity of the two enantiomers of a chi... more The increased awareness of the differences in biological activity of the two enantiomers of a chiral drug has raised the demand for enantiomerically pure products, particularly in the pharmaceutical industry. Simulated moving-bed chromatography can be used for the separation of the two enantiomers of a chiral molecule, which is feasible at all production scales, from laboratory to pilot to production plant. The use of non-enantioselective synthesis of racemic mixtures and simulated moving-bed enantiomer separation might make the development process of a new chiral drug substantially shorter and cheaper.

Journal of Chromatography A, 1999

The gas chromatographic enantiomer separation of a-ionone was studied with three different chiral... more The gas chromatographic enantiomer separation of a-ionone was studied with three different chiral stationary phases using as chiral selectors: (1) heptakis(2,3,6-triO methyl)-b-cyclodextrin, dissolved in polysiloxane PS-086, (2) octakis(2,6-di-Opentyl-3-O-trifluoroacetyl)-g-cyclodextrin and (3) octakis(2,6-di-O-pentyl-3-O-butanoyl)-g-cyclodextrin, both dissolved in polysiloxane SE-54. The influence of the concentration of the chiral selector in the polysiloxane, coated on Chromosorb P AW-DMCS 80-100 mesh, is described and discussed, as well as the effect of Chromosorb loading. The feasibility of the preparative gas chromatographic separation of the enantiomers of a-ionone is considered; in order to provide a term of comparison, the estimated performances are compared with those achieved in the separation of the enantiomers of the inhalation anaesthetic enflurane.

Journal of Chromatography A, 1997

The preparative enantiomeric separation of the inhalation anesthetics enflurane (1) and isofluran... more The preparative enantiomeric separation of the inhalation anesthetics enflurane (1) and isoflurane (2) in very high chemical (.99.5%) and enantiomeric excess (ee.99%) by gas chromatography (GC) on octakis(3-O-butanoyl-2,6-di-O-npentyl)-g-cyclodextrin (4), dissolved in the apolar polysiloxane SE-54 and coated on Chromosorb P AW DMCS, is described. Up to 1 g of each enantiomer of 1-2 can been obtained per diem. The enantiomers of the highly volatile desflurane (3) can also be separated, albeit with diminished ee. The enantiomeric excess of 1-3 was checked by analytical GC on 4 and the absolute configuration of 2 and 3 has been determined via anomalous X-ray diffraction.

Helvetica Chimica Acta, 2004

ABSTRACT

Electrophoresis, 1998

Dual chiral recognition system involving cyclodextrin derivatives in capillary electrophoresis 11... more Dual chiral recognition system involving cyclodextrin derivatives in capillary electrophoresis 11. Enhancement of enantioselectivity"

Electrophoresis, 1997

f3-Cyclodextrin, 1, can act as a chiral buffer additive in capillary zone electrophoresis (CZE) o... more f3-Cyclodextrin, 1, can act as a chiral buffer additive in capillary zone electrophoresis (CZE) owing to its ability to form diastereomeric complexes with the enantiomers of ionic compounds. Reaction of 1 with 2,3-epoxy-propyltrimethylammonium chloride gave preponderantly 6-0-(2-hydroxy-3-trimethylammoniopropyl) derivatives (2) of varying degrees of substitution (d.s.). Analogous reaction of 1 with 1,3-propanesultone yielded 6-0-(sulfo-n-propyl) derivatives (SPE-0-CD, 3) of varying d.s. The purity and the d.s. of 2 and 3 were determined by 'H NMR and electrospray ionization mass spectrometry (ESI-MS). These charged B-cyclodextrin derivatives were used for the chromatographic enantiomer separation of a series of neutral barbiturates, of chlorthalidone, terbutaline, warfarin, salbutamol and brompheniramine by cyclodextrin electrokinetic chromatography (CD-EKC). During the separation of chlorthalidone with 3 as chiral additive, a reversible interconversion of the enantiomers (enantiomerization)

Chemical Engineering Science, 2000

A gas chromatographic simulated moving-bed (SMB) laboratory unit for the separation of volatile e... more A gas chromatographic simulated moving-bed (SMB) laboratory unit for the separation of volatile enantiomers has been realized and the continuous gas chromatographic separation of the enantiomers of the volatile inhalation anesthetic en#urane has been performed. A chiral stationary phase based on a-cyclodextrin derivative, dissolved in an apolar polysiloxane and coated on Chromosorb particles has been used. The particle size has been carefully selected for the desired separation. Several experiments were performed at 353C with di!erent #ow rates and switch times, leading to di!erent separation regimes, including complete separation of the two enantiomers. The experimental results are presented and discussed in the light of the theoretical understanding of GC-SMB behavior.

Angewandte Chemie International Edition in English, 1996

... G Vernice. J. A m C/ioii. Snc. 1992. 114. ... 34. 122 223 [17] Influence of Anchor Lipids on ... more ... G Vernice. J. A m C/ioii. Snc. 1992. 114. ... 34. 122 223 [17] Influence of Anchor Lipids on the Homogeneity and Mobility of Lipid Bilayers on Thin Polymer Films Dierk Beyer, Gunther Elender, Wolfgang Knoll, Martin Kiihner, Steffen Maus, Helmut Ringsdorf,* and Erich Sackmann ...

Optimization in HPLC, 2021

Molecules (Basel, Switzerland), Jan 10, 2016

The identification of novel pan-sigma receptor (SR) modulators, potentially useful in cancer trea... more The identification of novel pan-sigma receptor (SR) modulators, potentially useful in cancer treatment, represents a new goal of our research. Here, we report on the preparation of novel chiral compounds characterized by a 3-C alkyl chain bridging an aromatic portion to a 4-benzyl-piperidine moiety. All of the studied compounds have been prepared both in racemic and enantiomerically-pure form, with the final aim to address the role of chirality in the SR interaction. To isolate and characterize enantiomeric compounds, high-performance liquid chromatography (HPLC) procedures were set up. A systematic analytical screening, involving several combinations of chiral stationary and mobile phases, allowed us to optimize the analytical resolution and to set up the (semi-)preparative chromatographic conditions. Applying the optimized procedure, the enantiomeric resolution of the studied compounds was successfully achieved, obtaining all of the compounds with an enantiomeric excess higher tha...

Journal of Chromatography B: Biomedical Sciences and Applications, 1999

The quantitative analysis of the chiral volatile anesthetic isoflurane (1) for biomedical applica... more The quantitative analysis of the chiral volatile anesthetic isoflurane (1) for biomedical applications by means of enantioselective gas chromatography (mass sensitive detector, selected ion monitoring) was studied. Two methods for the quantification of the enantiomers in blood samples drawn during and after narcosis were compared. Either the isomeric enflurane (2) was selected as an internal standard or a single enantiomer of 1 was used for the standard addition method, an approach referred to as 'enantiomer labeling'. Concentrations up to 0.3 micromol/l of the single enantiomers could be differentiated two days after anesthesia. The presented data imply that the body clearance for (+)-(S)-1 and (-)-(R)-1 proceeds to a measurable degree of enantioselectivity.

Recueil des Travaux Chimiques des Pays-Bas, 2010

ABSTRACT

Practical Gas Chromatography, 2014

Enantioselective GC is of widespread use in the enantiomeric analysis of volatile natural product... more Enantioselective GC is of widespread use in the enantiomeric analysis of volatile natural products such as pheromones, flavors, fragrances, and essential oils as well as synthetic products obtained from asymmetric syntheses and kinetic resolutions. Whereas enantioseparation of derivatized α-amino acids is performed on chiral stationary phases (CSPs) based on α-amino acid derivatives, alkylated/acylated cyclodextrins are employed as versatile CSPs for a multitude of volatile derivatized and nonderivatized enantiomers. Three main types of CSPs are reviewed and the miniaturization of enantioselective GC, the quantification of enantiomers, and validation issues are described. A list of commercially available fused silica capillary columns coated with various CSPs is compiled.

The enantiomers of chiral anesthetics (enflurane, isoflurane, desflurane) can be recognized, and,... more The enantiomers of chiral anesthetics (enflurane, isoflurane, desflurane) can be recognized, and, additionally, extremely low concentrations of all common inhalation anesthetics in ambient air can be monitored using simple on-line-operable gas sensors with cyclodextrin coatings.

The Journal of Physical Chemistry A, 2004

Three closely related previously synthesized monoaza[5]helicenes have been resolved into their en... more Three closely related previously synthesized monoaza[5]helicenes have been resolved into their enantiomers via enantioselective HPLC using a cellulose-derivative Chiralcel OD column. Circular dichroism (CD) spectra of the enantiomerically enriched samples have been recorded and assigned. The spectra were analyzed as a function of time, and different rate constants were found in the kinetics of racemization for the three molecules. Ab initio DFT calculations for the ground electronic states were employed to determine minima and saddle point structures and to understand the racemization process. The theoretical geometries compared well with those from X-ray structures. CD spectra were calculated by TD-DFT ab initio methods, and compared with experimental data.

Separation Science and Technology, 2002

The propensity of helical homochiral polymers derived from amylose to resolve optical isomers is ... more The propensity of helical homochiral polymers derived from amylose to resolve optical isomers is being exploited intensively for the production of active pharmaceutical ingredients (APIs), using either high performance lipid chromatography (HPLC) or the simulated moving bed (SMB) principle. Several lots of an amylose derived stationary phase, Chiralpak AS™, and its successor, Chiralpak AS-V™, were compared by pulse injections with

Journal of Chromatography A, 2003

The preparative chromatographic resolution of racemates has become over the past few years a stan... more The preparative chromatographic resolution of racemates has become over the past few years a standard approach for the generation of enantiomers in pharmaceutical research and development. This paper will discuss the chromatographic resolution of a racemic pharmaceutical intermediate. Initial analytical method development to determine the best preparative conditions will be presented. Batch resolution of kg quantities of racemate followed by the simulated moving bed resolution of tens and hundreds of kg of racemate will also be discussed. Finally the different approaches used for the separation will be compared.

Journal of Chromatography A, 2005

Simulated moving bed (SMB) chromatography is often perceived in the pharmaceutical industry as ch... more Simulated moving bed (SMB) chromatography is often perceived in the pharmaceutical industry as chromatographic method for separating binary mixtures, like racemates. However, SMB can also be used for unbalanced separations, i.e. binary mixtures of varying compositions and multi-component mixtures. These less common application modes of isocratic SMB chromatography are exemplified for four different compounds (racemates and diastereomers) and discussed in view of the so-called 'triangle theory' from an industrial perspective.

Journal of Chromatography A, 2005

Polymeric capillaries made from polyether ether ketone (PEEK) or ethylene-tetrafluoroethylene cop... more Polymeric capillaries made from polyether ether ketone (PEEK) or ethylene-tetrafluoroethylene copolymer (Tefzel) are considered as highly inert and chemically resistant materials used as standard equipment in HPLC and simulated moving bed (SMB) applications. During several racemate separations using a SMB unit equipped with these tubes a formation of micro-holes was observed. All separations had in common that a high content of an alkane was used in the mobile phase. The patterns of damage and possible reasons causing the leakages of the capillaries are discussed. Polymeric tubing had to be replaced by stainless steel capillaries for the enantiomer separations in order to ensure safety of workers, GMP status of products and control leakages.

Trends in Biotechnology, 2000

The increased awareness of the differences in biological activity of the two enantiomers of a chi... more The increased awareness of the differences in biological activity of the two enantiomers of a chiral drug has raised the demand for enantiomerically pure products, particularly in the pharmaceutical industry. Simulated moving-bed chromatography can be used for the separation of the two enantiomers of a chiral molecule, which is feasible at all production scales, from laboratory to pilot to production plant. The use of non-enantioselective synthesis of racemic mixtures and simulated moving-bed enantiomer separation might make the development process of a new chiral drug substantially shorter and cheaper.

Journal of Chromatography A, 1999

The gas chromatographic enantiomer separation of a-ionone was studied with three different chiral... more The gas chromatographic enantiomer separation of a-ionone was studied with three different chiral stationary phases using as chiral selectors: (1) heptakis(2,3,6-triO methyl)-b-cyclodextrin, dissolved in polysiloxane PS-086, (2) octakis(2,6-di-Opentyl-3-O-trifluoroacetyl)-g-cyclodextrin and (3) octakis(2,6-di-O-pentyl-3-O-butanoyl)-g-cyclodextrin, both dissolved in polysiloxane SE-54. The influence of the concentration of the chiral selector in the polysiloxane, coated on Chromosorb P AW-DMCS 80-100 mesh, is described and discussed, as well as the effect of Chromosorb loading. The feasibility of the preparative gas chromatographic separation of the enantiomers of a-ionone is considered; in order to provide a term of comparison, the estimated performances are compared with those achieved in the separation of the enantiomers of the inhalation anaesthetic enflurane.

Journal of Chromatography A, 1997

The preparative enantiomeric separation of the inhalation anesthetics enflurane (1) and isofluran... more The preparative enantiomeric separation of the inhalation anesthetics enflurane (1) and isoflurane (2) in very high chemical (.99.5%) and enantiomeric excess (ee.99%) by gas chromatography (GC) on octakis(3-O-butanoyl-2,6-di-O-npentyl)-g-cyclodextrin (4), dissolved in the apolar polysiloxane SE-54 and coated on Chromosorb P AW DMCS, is described. Up to 1 g of each enantiomer of 1-2 can been obtained per diem. The enantiomers of the highly volatile desflurane (3) can also be separated, albeit with diminished ee. The enantiomeric excess of 1-3 was checked by analytical GC on 4 and the absolute configuration of 2 and 3 has been determined via anomalous X-ray diffraction.

Helvetica Chimica Acta, 2004

ABSTRACT

Electrophoresis, 1998

Dual chiral recognition system involving cyclodextrin derivatives in capillary electrophoresis 11... more Dual chiral recognition system involving cyclodextrin derivatives in capillary electrophoresis 11. Enhancement of enantioselectivity"

Electrophoresis, 1997

f3-Cyclodextrin, 1, can act as a chiral buffer additive in capillary zone electrophoresis (CZE) o... more f3-Cyclodextrin, 1, can act as a chiral buffer additive in capillary zone electrophoresis (CZE) owing to its ability to form diastereomeric complexes with the enantiomers of ionic compounds. Reaction of 1 with 2,3-epoxy-propyltrimethylammonium chloride gave preponderantly 6-0-(2-hydroxy-3-trimethylammoniopropyl) derivatives (2) of varying degrees of substitution (d.s.). Analogous reaction of 1 with 1,3-propanesultone yielded 6-0-(sulfo-n-propyl) derivatives (SPE-0-CD, 3) of varying d.s. The purity and the d.s. of 2 and 3 were determined by 'H NMR and electrospray ionization mass spectrometry (ESI-MS). These charged B-cyclodextrin derivatives were used for the chromatographic enantiomer separation of a series of neutral barbiturates, of chlorthalidone, terbutaline, warfarin, salbutamol and brompheniramine by cyclodextrin electrokinetic chromatography (CD-EKC). During the separation of chlorthalidone with 3 as chiral additive, a reversible interconversion of the enantiomers (enantiomerization)

Chemical Engineering Science, 2000

A gas chromatographic simulated moving-bed (SMB) laboratory unit for the separation of volatile e... more A gas chromatographic simulated moving-bed (SMB) laboratory unit for the separation of volatile enantiomers has been realized and the continuous gas chromatographic separation of the enantiomers of the volatile inhalation anesthetic en#urane has been performed. A chiral stationary phase based on a-cyclodextrin derivative, dissolved in an apolar polysiloxane and coated on Chromosorb particles has been used. The particle size has been carefully selected for the desired separation. Several experiments were performed at 353C with di!erent #ow rates and switch times, leading to di!erent separation regimes, including complete separation of the two enantiomers. The experimental results are presented and discussed in the light of the theoretical understanding of GC-SMB behavior.

Angewandte Chemie International Edition in English, 1996

... G Vernice. J. A m C/ioii. Snc. 1992. 114. ... 34. 122 223 [17] Influence of Anchor Lipids on ... more ... G Vernice. J. A m C/ioii. Snc. 1992. 114. ... 34. 122 223 [17] Influence of Anchor Lipids on the Homogeneity and Mobility of Lipid Bilayers on Thin Polymer Films Dierk Beyer, Gunther Elender, Wolfgang Knoll, Martin Kiihner, Steffen Maus, Helmut Ringsdorf,* and Erich Sackmann ...

Optimization in HPLC, 2021

Molecules (Basel, Switzerland), Jan 10, 2016

The identification of novel pan-sigma receptor (SR) modulators, potentially useful in cancer trea... more The identification of novel pan-sigma receptor (SR) modulators, potentially useful in cancer treatment, represents a new goal of our research. Here, we report on the preparation of novel chiral compounds characterized by a 3-C alkyl chain bridging an aromatic portion to a 4-benzyl-piperidine moiety. All of the studied compounds have been prepared both in racemic and enantiomerically-pure form, with the final aim to address the role of chirality in the SR interaction. To isolate and characterize enantiomeric compounds, high-performance liquid chromatography (HPLC) procedures were set up. A systematic analytical screening, involving several combinations of chiral stationary and mobile phases, allowed us to optimize the analytical resolution and to set up the (semi-)preparative chromatographic conditions. Applying the optimized procedure, the enantiomeric resolution of the studied compounds was successfully achieved, obtaining all of the compounds with an enantiomeric excess higher tha...

Journal of Chromatography B: Biomedical Sciences and Applications, 1999

The quantitative analysis of the chiral volatile anesthetic isoflurane (1) for biomedical applica... more The quantitative analysis of the chiral volatile anesthetic isoflurane (1) for biomedical applications by means of enantioselective gas chromatography (mass sensitive detector, selected ion monitoring) was studied. Two methods for the quantification of the enantiomers in blood samples drawn during and after narcosis were compared. Either the isomeric enflurane (2) was selected as an internal standard or a single enantiomer of 1 was used for the standard addition method, an approach referred to as 'enantiomer labeling'. Concentrations up to 0.3 micromol/l of the single enantiomers could be differentiated two days after anesthesia. The presented data imply that the body clearance for (+)-(S)-1 and (-)-(R)-1 proceeds to a measurable degree of enantioselectivity.

Recueil des Travaux Chimiques des Pays-Bas, 2010

ABSTRACT

Practical Gas Chromatography, 2014

Enantioselective GC is of widespread use in the enantiomeric analysis of volatile natural product... more Enantioselective GC is of widespread use in the enantiomeric analysis of volatile natural products such as pheromones, flavors, fragrances, and essential oils as well as synthetic products obtained from asymmetric syntheses and kinetic resolutions. Whereas enantioseparation of derivatized α-amino acids is performed on chiral stationary phases (CSPs) based on α-amino acid derivatives, alkylated/acylated cyclodextrins are employed as versatile CSPs for a multitude of volatile derivatized and nonderivatized enantiomers. Three main types of CSPs are reviewed and the miniaturization of enantioselective GC, the quantification of enantiomers, and validation issues are described. A list of commercially available fused silica capillary columns coated with various CSPs is compiled.

The enantiomers of chiral anesthetics (enflurane, isoflurane, desflurane) can be recognized, and,... more The enantiomers of chiral anesthetics (enflurane, isoflurane, desflurane) can be recognized, and, additionally, extremely low concentrations of all common inhalation anesthetics in ambient air can be monitored using simple on-line-operable gas sensors with cyclodextrin coatings.

The Journal of Physical Chemistry A, 2004

Three closely related previously synthesized monoaza[5]helicenes have been resolved into their en... more Three closely related previously synthesized monoaza[5]helicenes have been resolved into their enantiomers via enantioselective HPLC using a cellulose-derivative Chiralcel OD column. Circular dichroism (CD) spectra of the enantiomerically enriched samples have been recorded and assigned. The spectra were analyzed as a function of time, and different rate constants were found in the kinetics of racemization for the three molecules. Ab initio DFT calculations for the ground electronic states were employed to determine minima and saddle point structures and to understand the racemization process. The theoretical geometries compared well with those from X-ray structures. CD spectra were calculated by TD-DFT ab initio methods, and compared with experimental data.

Separation Science and Technology, 2002

The propensity of helical homochiral polymers derived from amylose to resolve optical isomers is ... more The propensity of helical homochiral polymers derived from amylose to resolve optical isomers is being exploited intensively for the production of active pharmaceutical ingredients (APIs), using either high performance lipid chromatography (HPLC) or the simulated moving bed (SMB) principle. Several lots of an amylose derived stationary phase, Chiralpak AS™, and its successor, Chiralpak AS-V™, were compared by pulse injections with

Journal of Chromatography A, 2003

The preparative chromatographic resolution of racemates has become over the past few years a stan... more The preparative chromatographic resolution of racemates has become over the past few years a standard approach for the generation of enantiomers in pharmaceutical research and development. This paper will discuss the chromatographic resolution of a racemic pharmaceutical intermediate. Initial analytical method development to determine the best preparative conditions will be presented. Batch resolution of kg quantities of racemate followed by the simulated moving bed resolution of tens and hundreds of kg of racemate will also be discussed. Finally the different approaches used for the separation will be compared.

Journal of Chromatography A, 2005

Simulated moving bed (SMB) chromatography is often perceived in the pharmaceutical industry as ch... more Simulated moving bed (SMB) chromatography is often perceived in the pharmaceutical industry as chromatographic method for separating binary mixtures, like racemates. However, SMB can also be used for unbalanced separations, i.e. binary mixtures of varying compositions and multi-component mixtures. These less common application modes of isocratic SMB chromatography are exemplified for four different compounds (racemates and diastereomers) and discussed in view of the so-called 'triangle theory' from an industrial perspective.

Journal of Chromatography A, 2005

Polymeric capillaries made from polyether ether ketone (PEEK) or ethylene-tetrafluoroethylene cop... more Polymeric capillaries made from polyether ether ketone (PEEK) or ethylene-tetrafluoroethylene copolymer (Tefzel) are considered as highly inert and chemically resistant materials used as standard equipment in HPLC and simulated moving bed (SMB) applications. During several racemate separations using a SMB unit equipped with these tubes a formation of micro-holes was observed. All separations had in common that a high content of an alkane was used in the mobile phase. The patterns of damage and possible reasons causing the leakages of the capillaries are discussed. Polymeric tubing had to be replaced by stainless steel capillaries for the enantiomer separations in order to ensure safety of workers, GMP status of products and control leakages.