
Preparative Enantioselective Chromatography
by Cox, Geoffrey B.Buy New
Rent Textbook
Rent Digital
Used Textbook
We're Sorry
Sold Out
How Marketplace Works:
- This item is offered by an independent seller and not shipped from our warehouse
- Item details like edition and cover design may differ from our description; see seller's comments before ordering.
- Sellers much confirm and ship within two business days; otherwise, the order will be cancelled and refunded.
- Marketplace purchases cannot be returned to eCampus.com. Contact the seller directly for inquiries; if no response within two days, contact customer service.
- Additional shipping costs apply to Marketplace purchases. Review shipping costs at checkout.
Summary
Author Biography
(Editor)VP & General Manager, Separation Solutions
Table of Contents
Contributors | p. xi |
Preface | p. xiii |
Chiral chromatography in support of pharmaceutical process research | p. 1 |
Introduction | p. 1 |
A brief introduction to chirality | p. 1 |
Why chirality is important | p. 2 |
Accessing enantiopurity: a brief overview of approaches | p. 2 |
Enantiopure starting materials: the chiral pool | p. 2 |
Removable enantioenriched auxiliaries | p. 3 |
Enantioselective catalysis | p. 3 |
Resolution technologies: introduction | p. 4 |
Chromatographic productivity is the key metric for preparative chromatography | p. 7 |
Stationary phases for preparative chiral chromatography | p. 8 |
Advantages of preparative chiral chromatography over other approaches for accessing enantiopure materials | p. 8 |
Simulated moving bed enantioseparation | p. 9 |
Green enantioseparation | p. 9 |
What is the appropriate role of preparative chromatography in organic synthesis? | p. 10 |
Fording the river at the easiest point: some observations on the appropriate placement of a chromatographic resolution within a chiral synthesis | p. 11 |
Origins of preparative chiral chromatography | p. 12 |
Practical tips for preparative chromatographic enantioseparation | p. 13 |
Conclusion | p. 15 |
Introduction to preparative chromatography | p. 19 |
Introduction | p. 19 |
Adsorption isotherms | p. 19 |
The simple case - the Langmuir isotherm | p. 20 |
Other isotherms | p. 22 |
Competitive isotherms | p. 24 |
Kinetics | p. 31 |
Metrics for preparative operations | p. 34 |
Throughput | p. 34 |
Production rate | p. 35 |
Productivity | p. 35 |
Specific productivity | p. 35 |
Cost | p. 36 |
The influence of chromatographic parameters on preparative chromatography | p. 36 |
Effect of particle size on preparative performance | p. 36 |
Effects of pressure | p. 38 |
Effects of column efficiency | p. 39 |
Effect of column length | p. 40 |
The effects of selectivity | p. 42 |
Economics of preparative separations | p. 44 |
Point of insertion of the chromatographic resolution in the synthetic route | p. 46 |
Chiral stationary phases for preparative enantioselective chromatography | p. 48 |
Summary | p. 48 |
Introduction | p. 48 |
Historical development of CSPs for preparative chromatography | p. 49 |
Preparative CSPs | p. 52 |
Classification of CSPs | p. 52 |
Polymeric phases | p. 53 |
Brush-type CSPs | p. 59 |
Chiral phases for ligand-exchange chromatography | p. 60 |
Imprinted phases | p. 62 |
Chemical and physical properties of CSPs | p. 62 |
Loading capacity | p. 62 |
Chemical and physical stability | p. 63 |
Solubility of the chiral solute | p. 65 |
New and future developments in the field of preparative CSPs | p. 65 |
CSPs with improved loading capacity | p. 66 |
CSPs with improved selectivity | p. 66 |
Immobilised polysaccharide-based CSPs | p. 69 |
Conclusion | p. 70 |
Method development for preparative enantioselective chromatography | p. 78 |
Introduction | p. 78 |
Chiral stationary phases for enantioselective chromatography | p. 78 |
Screening and optimisation strategy for preparative chiral chromatography | p. 80 |
Choice of the stationary phase | p. 81 |
Choice of the mobile phase | p. 82 |
Screening and optimisation of specific phases | p. 87 |
Additives in the mobile phase | p. 88 |
Preparative separations, criteria and objectives | p. 89 |
Loadability and productivity | p. 89 |
Selectivity and productivity | p. 93 |
Solubility and productivity | p. 97 |
Viscosity and productivity | p. 99 |
Chemical and enantiomeric stability | p. 100 |
Scale-up issues | p. 101 |
Laboratory-scale separations | p. 101 |
Large-scale separations | p. 103 |
Conclusion | p. 108 |
Scaling-up of preparative chromatographic enantiomer separations | p. 110 |
Introduction | p. 110 |
Analytical screening models | p. 111 |
Standard procedure | p. 111 |
Fast analytical screening process | p. 113 |
Scaling-up from milligram to kilogram quantities | p. 115 |
Introduction | p. 115 |
Separation of a xanthone derivative | p. 115 |
Separation of 'dibenzocycloheptanol' derivative | p. 117 |
Separation of a 'pyrido-pyrimidin-4-one' derivative | p. 121 |
Separation of a piperazinyl-piperidine derivative | p. 125 |
Summary - scale-up | p. 126 |
Larger scale separations | p. 127 |
Introduction | p. 127 |
Separation of a 'pyrolidino-quinolinone' derivative | p. 127 |
Scale-up problems in early development | p. 133 |
Introduction | p. 133 |
Separation of a 'tetracyclic' compound | p. 135 |
Non-natural amino acids | p. 138 |
Separation of an 'indole' derivative | p. 146 |
Summary | p. 148 |
General conclusions | p. 148 |
Steady-state recycling and its use in chiral separations | p. 149 |
Overview | p. 149 |
Introduction | p. 149 |
SSR - concept and operation | p. 150 |
Concept | p. 150 |
Operation | p. 151 |
Role of the injection loop | p. 152 |
Case studies | p. 153 |
Case study 1 | p. 153 |
Case study 2 | p. 163 |
Case study 3: collection of three SSR fractions | p. 171 |
Conclusions | p. 174 |
Simulated moving bed and related techniques | p. 176 |
Overview | p. 176 |
The SMB concept | p. 176 |
Modeling of SMB processes | p. 180 |
Design of SMB processes | p. 182 |
Simulation of SMB processes | p. 184 |
Influence of the equilibrium adsorption isotherms | p. 185 |
Influence of mass transfer resistance | p. 192 |
SMB related techniques | p. 192 |
Varicol processes | p. 192 |
Pseudo-SMB processes | p. 198 |
Preparative-scale supercritical fluid chromatography | p. 205 |
Introduction | p. 205 |
History of SFC at GlaxoSmithKline | p. 205 |
Principles of SFC | p. 206 |
Advantages of SFC | p. 208 |
Drawbacks of preparative SFC | p. 209 |
Use of SFC | p. 212 |
Chiral separation using SFC | p. 213 |
Achiral separation using SFC | p. 215 |
Consideration of preparative SFC | p. 219 |
Future direction and development | p. 219 |
Conclusion | p. 220 |
Equipment for preparative and large size enantioselective chromatography | p. 224 |
Introduction | p. 224 |
The heart of the chromatographic process: the column | p. 225 |
Packing technique, bed formation and bed consolidation | p. 226 |
The wall region | p. 227 |
Heat dissipation | p. 228 |
Column technology | p. 229 |
Column design | p. 231 |
Equipment considerations for batch chromatography | p. 233 |
Recycling | p. 233 |
Detection | p. 234 |
Supercritical fluid chromatography | p. 235 |
Principle | p. 235 |
Technical aspects | p. 236 |
Eluent | p. 236 |
Pumping | p. 237 |
Injection | p. 238 |
Detection | p. 238 |
Product recovery | p. 239 |
Eluent recycling | p. 240 |
High-pressure technology, safety aspects | p. 241 |
Multicolumn continuous chromatographic processes | p. 242 |
Simulated moving bed | p. 242 |
VARICOL | p. 246 |
Case study in production-scale multicolumn continuous chromatography | p. 253 |
Introduction | p. 253 |
Chromatographic process research | p. 253 |
Introduction | p. 253 |
Selection of racemate to separate | p. 253 |
Choice of the chromatographic conditions | p. 255 |
Choice of the separation technique | p. 257 |
Process development | p. 258 |
Optimisation of the chemical steps | p. 258 |
Production facts | p. 266 |
Introduction | p. 266 |
Implementation in a cGMP production environment | p. 267 |
Qualification | p. 268 |
Validation | p. 271 |
Production and maintenance data | p. 271 |
Further areas of development | p. 273 |
Contract manufacturing and outsourcing considerations | p. 277 |
Introduction | p. 277 |
The regulatory agencies and the chiral market | p. 278 |
Contract manufacturing | p. 280 |
Time constraints | p. 280 |
Risk of capital investment | p. 280 |
Expertise | p. 281 |
Intellectual property | p. 282 |
Location | p. 282 |
Primary or secondary supplier | p. 282 |
Selecting the outsourcing partner | p. 283 |
Expectations | p. 283 |
Audit | p. 283 |
Decision grid | p. 284 |
Communication | p. 284 |
Contact matrix | p. 285 |
Frequent updates | p. 285 |
Project requirements | p. 285 |
R&D - method development | p. 285 |
Clinical trial quantities | p. 287 |
Trial runs vs production runs | p. 287 |
Commercial-scale quantities | p. 288 |
Schedule | p. 289 |
Quantity | p. 289 |
Product quality | p. 290 |
Transfer of information | p. 291 |
Feed characterization | p. 291 |
Separation conditions | p. 293 |
The chiral stationary phase | p. 294 |
Analytical methods | p. 295 |
Impurity specifications | p. 296 |
Final product | p. 296 |
Other considerations | p. 296 |
End of the project | p. 297 |
Economics | p. 297 |
Productivity | p. 297 |
Production rate | p. 298 |
Cost breakdown | p. 298 |
Clinical trial quantities | p. 300 |
Commercial-scale quantities | p. 301 |
Conclusion | p. 302 |
Advanced concepts | p. 303 |
Index | p. 325 |
Table of Contents provided by Ingram. All Rights Reserved. |
An electronic version of this book is available through VitalSource.
This book is viewable on PC, Mac, iPhone, iPad, iPod Touch, and most smartphones.
By purchasing, you will be able to view this book online, as well as download it, for the chosen number of days.
Digital License
You are licensing a digital product for a set duration. Durations are set forth in the product description, with "Lifetime" typically meaning five (5) years of online access and permanent download to a supported device. All licenses are non-transferable.
More details can be found here.
A downloadable version of this book is available through the eCampus Reader or compatible Adobe readers.
Applications are available on iOS, Android, PC, Mac, and Windows Mobile platforms.
Please view the compatibility matrix prior to purchase.