Chiral Chromatography

by Beesley, Thomas E.; Scott, Raymond P. W.

• ISBN13: 9780471974277
• ISBN10: 0471974277
• Edition: 1st
• Format: Hardcover
• Copyright: 1999-01-26
• Publisher: WILEY

Summary

Chiral Chromatography Thomas E. Beesley Advanced Separation Technologies Inc., Whippany, New Jersey, USA Raymond P. W. Scott Chemistry Department, Georgetown University, Washington DC, USA and Chemistry Department, Birkbeck College, University of London, UK Analytical techniques based on separation processes, such as chromatography and electrophoresis, are finding a growing range of applications in chemical, pharmaceutical and clinical laboratories. The Wiley Separation Science Series provides the analyst in these laboratories with well-focused books covering individual techniques, so that they can be applied more efficiently and effectively to contemporary analytical problems. The different enantiomers of a drug can exhibit widely different physiological activity in degree and nature. As a result, the separation and identification of enantiomers is now a very important analytical problem and chiral chromatography is the natural technique to apply to the resolution of such mixtures. Chiral Chromatography provides the reader with a basic understanding of the nature of chromatographic separations and relates the principles specifically to the separation of enantiomers. The following information is included:* chiral separations involving both gas and liquid chromatography* descriptions of the apparatus used for both techniques* detailed discussion on the retention mechanism that results in chiral selectivity* the structure and synthesis of a wide range of chirally active stationary phases used in both gas and liquid chromatography* preparative applications for large scale purification of enantiomers* applications of capillary electrophoresis and capillary electrochromatography.In addition to the above, a large number of examples of the separation of both commercially and physiologically interesting chiral mixtures are given, as is a detailed discussion on the mechanism of selectivity of each example. Thomas Beesley was founder and is the CEO for a leading manufacturer of chiral stationary phases and has published papers on TLC, HPLC and chiral separations involving cyclodextrins. He has also coauthored papers with Daniel W. Armstrong, an expert on modern cyclodextrin columns. Raymond Scott has worked in the field of separation science for over 40 years and has contributed extensively to the development of both gas and liquid chromatography publishing over 160 papers on the subjects.

Author Biography

Thomas E. Beesley Advanced Separation Technologies Inc., Whippany, New Jersey, USA Raymond P.W. Scott Chemistry Department, Georgetown University, Washington DC, USA and Chemistry Department, Birkbeck College, University of London, UK

Table of Contents

Chapter 1 An Introduction to Chiral Chromatography	1	(28)
An Historical Perspective	1	(2)
A Short Introduction to Stereochemistry	3	(12)
Polarization Modulation	7	(1)
Practical Chiral Measuring Devices	8	(7)
Configuration Specifications	15	(8)
Diastereoisomers	18	(2)
Anomers	20	(1)
Epimers	20	(2)
Meso Structures	22	(1)
Separation Techniques for Chiral Chemistry	23	(2)
Synopsis	25	(2)
References	27	(2)
CHAPTER 2 Mechanism of Solute Retention	29	(24)
The Plate Theory	30	(4)
The Retention Volume of a Solute	34	(5)
The Capacity Ratio of a Solute	37	(1)
The Separation Ratio	38	(1)
The Thermodynamic Properties of the Distribution Coefficient	39	(8)
The Availability of the Stationary Phase	47	(3)
Synopsis	50	(1)
References	51	(2)
Chapter 3 Molecular Interactions	53	(26)
Dispersion Forces	54	(2)
Polar Forces	56	(4)
Dipole-Dipole Interactions	57	(2)
Dipole-Induced-Dipole Interactions	59	(1)
Ionic Forces	60	(1)
Hydrophobic and Hydrophilic Interactions	61	(4)
Molecular Interactions in Mixed Phases	65	(11)
Chiral Additives	72	(4)
Synopsis	76	(1)
References	77	(2)
Chapter 4 The Basic Gas Chromatograph	79	(28)
Gas Supplies	81	(2)
Sampling Devices	83	(5)
Injection Systems for Packed Columns	83	(2)
Injection Systems for Small Diameter Capillary Columns	85	(1)
Injection Systems for Large Bore Capillary Columns	86	(2)
Automatic Injection Systems	88	(1)
The Column Oven and Temperature Programmer	88	(1)
Detectors	89	(6)
Detector Specifications	90	(3)
Detector Response	93	(1)
Detector Sensitivity or Minimum Detectable Concentration	93	(1)
Pressure Sensitivity	94	(1)
Flow Sensitivity	95	(1)
Temperature Sensitivity	95	(1)
The Flame Ionization Detector	95	(2)
The Nitrogen Phosphorous Detector (NPD)	97	(1)
The Electron Capture Detector	98	(3)
The Katharometer (Thermal Conductivity and Hot Wire) Detector	101	(2)
Data Acquisition and Processing	103	(1)
Synopsis	104	(2)
References	106	(1)
Chapter 5 GC Chiral Stationary Phases and Columns	107	(34)
Early Days in Chiral GC	108	(4)
Chiral stationary Phases for Gas Chromatography	112	(11)
Small Molecule Stationary Phases	112	(2)
Chiral Polysiloxane Stationary Phases	114	(2)
Chiral Metal Chelating Stationary Phases	116	(3)
Cyclodextrin Chiral Stationary Phases	119	(4)
Factors Controlling Selectivity	123	(1)
Open Tubular Columns	124	(5)
Dynamic Coating	125	(2)
Static Coating	127	(1)
Column Regeneration	127	(2)
Capillary Column Design and Choice	129	(7)
Stationary Phases for the GC Separation of Chiral Substances	136	(2)
Synopsis	138	(2)
References	140	(1)
Chapter 6 Chiral Gas Chromatography Applications	141	(32)
The Basic Principles of Chiral Selectivity	141	(2)
Test Mixtures	143	(3)
Elution Reversal of Enantiomers	146	(3)
Selectivity Characteristics of the Different Cyclodextrins	149	(5)
The Effect of Solute Derivatization on Chiral Selectivity	154	(2)
Chiral Separations of Essential Oils	156	(9)
Pharmaceutical Applications of Chiral Gas Chromatography	165	(4)
General Applications of Chiral Chromatography	169	(2)
Synopsis	171	(1)
References	172	(1)
Chapter 7 The Basic Liquid Chromatograph	173	(48)
The Basic LC Layout	173	(1)
Mobile Phase Reservoirs	174	(1)
The Solvent Programmer	175	(10)
The High-Pressure Mixing Solvent Programmer	175	(1)
The Low-Pressure Mixing Solvent Programmer	176	(1)
The Mobile Phase Pump	176	(2)
The Sample Valve	178	(3)
The Column and Column Oven	181	(4)
Liquid Chromatography Detectors	185	(1)
The UV Detector	185	(8)
The Fixed Wavelength Detector	187	(1)
The Multi-Wavelength Detector	188	(1)
The Diode Array Detector	189	(4)
The Electrical Conductivity Detector	193	(2)
The Fluorescence Detector	195	(2)
The Light Scattering Detectors	197	(7)
The Multiple Angle Laser Light-Scattering (MALS) Detector	201	(3)
The Refractive Index Detector	204	(3)
Chiral Detectors	207	(5)
Data Acquisition and Processing	212	(3)
Synopsis	215	(4)
References	219	(2)
Chapter 8 Liquid Chromatography Chiral Stationary Phases	221	(44)
Chiral Stationary Phases	229	(32)
Protein Based Stationary Phases	230	(5)
The Pirkle Type Stationary Phases	235	(4)
Coated Cellulose and Amylose Derivatives	239	(3)
Macrocyclic Glycopeptide Stationary Phases	242	(11)
Cyclodextrin Based Chiral Stationary Phases	253	(8)
Synopsis	261	(2)
References	263	(2)
Chapter 9 Preparation of LC Chiral Phases and Columns	265	(26)
The Supporting Matrix for Chiral Stationary Phases	265	(3)
The Preparation of Protein Stationary Phases	268	(2)
The Preparation of the Pirkle Stationary Phases	270	(3)
The Preparation of Cellulose and Amylose Stationary Phases	273	(2)
The Preparation of the Macrocyclic Glycopeptides Phases	275	(2)
The Preparation of the Cyclodextrin Based Stationary Phases	277	(4)
Column Packing Techniques	281	(8)
Mechanical Packing Equipment	286	(1)
Radial Compression Packing	287	(1)
Axial Compression Packing	288	(1)
Synopsis	289	(1)
References	290	(1)
Chapter 10 Column Temperature and Mobile Phase Composition: Their Effect on Column Length and Analysis Time	291	(26)
An Optimization Procedure for a Chiral Separation	297	(4)
The Experimental Determination of f(R)(X(Phi)), f(S)(X(Phi)), f(R)(T, X(Phi)) and f(S)(T, X(Phi))	301	(12)
Synopsis	313	(1)
References	314	(3)
Chapter 11 Chiral Liquid Chromatography Applications	317	(58)
The Protein Stationary Phases	318	(9)
The Separation of the Enantiomers of Epibatidine	321	(1)
Techniques for Improving the Detection Sensitivity of the Enantiomers of a Leukotriene Antagonist	322	(3)
The Separation of the Enantiomers of Vamicamide Contained in Blood Serum and Urine	325	(2)
The Pirkle Stationary Phases	327	(9)
The Separation of the Enantiomers of Some Amino Acids	327	(2)
The Effect of the Chain Length of the Mobile Phase Dispersive Solvent Component on Chiral Resolution	329	(2)
Stationary Phase Modification to Improve the Separation of Naproxen Enantiomers	331	(3)
The Separation of the Fullerenes	334	(2)
The Cellulose and Amylose Stationary Phases	336	(11)
The Separation of Some Chiral Drugs on Different Cellulose Derivatives	339	(3)
The Separation of the Enantiomers of Propranolol, Metroprolol and Atenolol	342	(2)
The Separation of the Enantiomers of Two Anticonvulsants	344	(3)
The Macrocyclic Glycopeptide Stationary Phases	347	(11)
The Separation of the Enantiomers of Three Racemic Substituted Pyidones	347	(2)
Examples of the use of Vancomycin in both the Normal Phase and Reverse Phase Modes	349	(5)
The Separation of the Enantiomers of Ibuprofen on Vancomycin	354	(1)
The Separation of the Isomers of Citalopram	355	(2)
The Separation of the Isomers of 2-and 3-Bromophenylalanine	357	(1)
The Cyclodextrin Based Stationary Phase	358	(13)
The use of a Cyclodextrin Based Stationary Phase to Separate Blocking Agents	358	(3)
The determination of Enantiomers in Blood Serum by Direct Injection	361	(1)
The Use of 2-Quinoxal Chloride for Precolumn Derivatization	362	(2)
The Separation of the Chlorophenols on Beta-Cyclodextrin Bonded Phase	364	(2)
The Separation of Major Soybean Phospholipids on Beta-Cyclodextrin Bonded Silica	366	(2)
The Separation of Porphyrins on a Gamma-Cyclodextrin Stationary Phase	368	(3)
Synopsis	371	(2)
References	372	(3)
Chapter 12 Preparative Chiral Chromatography	375	(38)
The Loading Capacity of a Column	376	(3)
The Maximum Sample Volume	379	(2)
Sample Volume Overload	381	(4)
Sample Mass Overload	385	(3)
Preparative Chromatography Apparatus	388	(4)
Solvent Reservoirs	389	(1)
Pumps	390	(1)
Sample Valves	390	(1)
Preparative Columns	390	(1)
Preparative Detectors	391	(1)
Fraction Collectors	391	(1)
Solvent Hazard	392	(1)
Packing Preparative Columns	392	(1)
Recycling Development	393	(4)
Alternative Preparative Techniques	397	(12)
The Moving Bed Continuous Chromatography System	398	(3)
The Simulated Moving Bed Preparative Chromatography System	401	(4)
Radial Flow Chromatography	405	(4)
The Preparative Separation of the Enantiomers of Chlorokynurenine	409	(1)
Synopsis	410	(1)
References	411	(2)
Chapter 13 Chiral Separations by Capillary Electrophoresis and Capillary Electrochromatography	413	(24)
Capillary Electrophoresis	413	(12)
Isotachophoresis	414	(1)
Isoelectric Focusing	415	(2)
Electro-osmotic Flow (Electro-endosmosis)	417	(8)
Application Examples	425	(8)
The Separation of Peptides	425	(2)
The Separation of the Stereoisomers of a Mixture of Pseudoephedrine and Ephedrine	427	(1)
The Effect of pH on the Separation of Duloxetine Enantiomers Using Hydroxypropyl-Beta-Cyclodextrin Additives	428	(1)
The Separation of the Enantiomers of Some Amino Acids with the Chiral Additive Vancomycin	429	(2)
The Separation of Some enantiomers by Counter Current Capillary Electrophoresis	431	(2)
Synopsis	433	(1)
References	434	(3)
Chapter 14 An Experimental Approach to Chiral Chromatography	437	(28)
Introduction	437	(2)
Chiral Gas Chromatography	439	(2)
Derivatization	439	(2)
The Polysiloxane Based Stationary Phases	441	(2)
The Amino Acid-Peptide Polysiloxane Stationary Phases	441	(1)
Peptide-Dimethylpolysiloxane Chiral Stationary Phases	442	(1)
Peptide-Phenylpolysiloxane Chiral Stationary Phases	442	(1)
Cyanopolysiloxane Peptide Chiral Stationary Phases	442	(1)
The Polysiloxane-cyclodextrin Based Stationary Phases	443	(3)
Chiral Liquid Chromatography	446	(1)
The Protein Based Stationary Phases	446	(5)
CHIRAL--AGP	447	(2)
CHIRAL--HSA	449	(2)
The Cellulose Based Stationary Phases	451	(3)
The Pirkle Stationary Phases	454	(3)
The Macrocyclic Glycopeptide Bonded Phases	457	(3)
The Cyclodextrin Bonded Phases	460	(5)
Bibliography	465	(32)
The Protein Phases	465	(8)
The Pirkle Stationary Phases	473	(3)
The Cellulose and Amylose Stationary Phases	476	(6)
The Macrocyclic Glycopeptide Stationary Phases	482	(1)
The Cyclodextrin Based Stationary Phases	483	(14)
Appendix	497	(2)
Index	499