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More About This Title Green Techniques for Organic Synthesis andMedicinal Chemistry
English
An updated overview of the rapidly developing field of green engineering techniques for organic synthesis and medicinal chemistry
Green chemistry remains a high priority in modern organic synthesis and pharmaceutical R&D, with important environmental and economic implications. This book presents comprehensive coverage of green chemistry techniques for organic and medicinal chemistry applications, summarizing the available new technologies, analyzing each technique’s features and green chemistry characteristics, and providing examples to demonstrate applications for green organic synthesis and medicinal chemistry.
The extensively revised edition of Green Techniques for Organic Synthesis and Medicinal Chemistry includes 7 entirely new chapters on topics including green chemistry and innovation, green chemistry metrics, green chemistry and biological drugs, and the business case for green chemistry in the generic pharmaceutical industry. It is divided into 4 parts. The first part introduces readers to the concepts of green chemistry and green engineering, global environmental regulations, green analytical chemistry, green solvents, and green chemistry metrics. The other three sections cover green catalysis, green synthetic techniques, and green techniques and strategies in the pharmaceutical industry.
Includes more than 30% new and updated material—plus seven brand new chaptersEdited by highly regarded experts in the field (Berkeley Cue is one of the fathers of Green Chemistry in Pharma) with backgrounds in academia and industryBrings together a team of international authors from academia, industry, government agencies, and consultancies (including John Warner, one of the founders of the field of Green Chemistry)
Green Techniques for Organic Synthesis and Medicinal Chemistry, Second Edition is an essential resource on green chemistry technologies for academic researchers, R&D professionals, and students working in organic chemistry and medicinal chemistry.
English
I INTRODUCTION 1
1 Green Toxicology 3
Nicholas D. Anastas
1.1 Introduction 3
1.2 History and Scope of Toxicology 4
1.2.1 The need for green toxicology 5
1.3 Principles of Toxicology 5
1.3.1 Characteristics of exposure 6
1.3.2 Spectrum of toxic effects 6
1.3.3 The dose–response relationship 7
1.4 Disposition of Toxicants in Organisms 8
1.4.1 Absorption 9
1.4.2 Distribution 11
1.4.3 Metabolism 11
1.4.4 Excretion 12
1.5 Nonorgan System Toxicity 12
1.5.1 Carcinogenesis 13
1.5.2 Reproductive and developmental toxicity 13
1.5.3 Immunotoxicology 14
1.6 Mechanistic Toxicology 15
1.7 Quantitative Structure–Activity Relationships 16
1.8 Environmental Toxicology 18
1.8.1 Persistence and bioaccumulation 18
1.9 Risk Assessment 19
1.9.1 NonCancer risk assessment 20
1.9.2 Cancer risk assessment 21
1.10 Conclusions 21
References 22
2 Green Chemistry and the Pharmaceutical Industry 25
Amy S. Cannon, Joseph L. Pont and John C. Warner
2.1 Introduction 25
2.2 Green Chemistry versus Sustainable Chemistry 26
2.3 Trend: The Ongoing Use of Hazardous Chemistry 27
2.4 Myth: To Do Green Chemistry One Must Sacrifice Performance and Cost 28
2.5 Green Chemistry and the Future of the Pharmaceutical Industry 29
2.6 Green Chemistry in Pharmaceutical Process Development and Manufacturing 30
2.7 Conclusions 30
References 31
II GREEN CATALYSIS 33
3 Environmental Science and Green Chemistry; Guiding Environmentally Preferred
Manufacturing, Materials, and Products 35
Richard T. Williams and Travis R. Williams
3.1 Introduction 35
3.2 Market Forces 36
3.2.1 Chemicals in the natural and human environment 37
3.2.2 Precautionary decision making 37
3.2.3 Chemical control laws 37
3.2.4 Green chemistry initiatives 38
3.2.5 Drug registration Environmental Risk Assessment (ERA) 39
3.2.6 Extended Producer Responsibility (EPR) 39
3.2.7 Ecosystem valuation 39
3.2.8 Company expectations 39
3.2.9 Public expectations 39
3.2.10 Environmental labeling, standards, and classification 39
3.3 Indicators (Attributes) of Environmental Performance 40
3.4 Environmental Impact 40
3.5 Strategic Approach to Greener Manufacturing Processes and Products 42
3.6 Manufacturing Process Improvements 43
3.6.1 Business and Professional Advantages from Manufacturing
Process Improvements 44
3.7 Product Improvements 45
3.8 Environmental Decision Making 46
3.8.1 E-factor 47
3.8.2 Process Mass Intensity (PMI) 47
3.8.3 Life Cycle Assessment (LCA) 47
3.8.4 Individual company initiatives 48
3.8.5 Environmental (Ecological) Risk Assessment (ERA) 49
3.8.6 Alternatives Assessment (AA)/Chemical Alternatives Assessment (CAA) 49
3.8.7 Green Screen 50
3.8.8 iSUSTAINTM Green chemistry index 50
3.8.9 Computational Science and Quantitative Structure–Activity
Relationships (QSARs) 51
3.8.10 Tiered testing 52
3.8.11 Databases and lists of chemicals 52
3.9 Case Study – Pharmaceuticals/Biologics 53
3.9.1 Pharmaceutical manufacturing 53
3.9.2 Pharmaceutical products 54
3.10 Case Study – Nanotechnology 58
3.11 Green Credentials and Environmental Standards 59
3.12 Inspiring Innovation – Academic and Industry Programs 60
3.12.1 Academic programs 60
3.12.2 Industry programs 60
3.13 Conclusions and Recommendations 61
References 64
4 Direct CH Bond Activation Reactions 69
Anna Tomin, Seema Bag and Bela T€or€ok
4.1 Introduction 69
4.2 Homogeneous CH Activation by Metal Complex Catalysis 70
4.2.1 Pd-catalyzed carbon–carbon bond formations 70
4.2.2 Pd-catalyzed carbon–heteroatom bond formation 73
4.2.3 CH activation by other metals 74
4.3 Heterogeneous Catalytic Methods for CH Activation 75
4.3.1 Supported metal complexes 75
4.3.2 Supported metals 78
4.4 CH Activation by Organocatalysts 80
4.5 Enzymatic CH Activations 83
References 87
5 Supported Asymmetric Organocatalysis 99
Long Zhang, Lingyun Cui, Sanzhong Luo and Jin-Pei Cheng
5.1 Introduction 99
5.2 Polymer-Supported Organocatalysts 99
5.2.1 Polymer-supported chiral amines for enamine and iminiun catalysis 99
5.2.2 Polymer-supported phase transfer catalysts 106
5.2.3 Polymer-supported phosphoric acid catalyst 107
5.2.4 Miscellaneous 108
5.3 Solid Acid-Supported Organocatalysis 108
5.3.1 Polyoxometalate-supported chiral amine catalysts 109
5.3.2 Solid sulfonic acid supported chiral amine catalysts 110
5.4 Ionic Liquid-Supported Organocatalysts 111
5.5 Magnetic Nanoparticle-Supported Organocatalysts 119
5.6 Silica-Supported Asymmetric Organocatalysts 119
5.6.1 Silica-supported proline and its derivatives 120
5.6.2 Silica-supported MacMillan catalysts 121
5.6.3 Other silica-supported organocatalysts 122
5.7 Clay Entrapped Organocatalysts 123
5.8 Miscellaneous 124
5.9 Conclusion 126
Acknowledgments 126
References 127
6 Fluorous Catalysis 137
Laszlo T. Mika and Istvan T. Horvath
6.1 Introduction and the Principles of Fluorous Catalysis 137
6.2 Ligands for Fluorous Transition Metal Catalysts 142
6.3 Synthetic Application of Fluorous Catalysis 142
6.3.1 Hydroformylation 142
6.3.2 Hydrogenation 147
6.3.3 Hydrosylilation 150
6.3.4 Cross-coupling reactions 154
6.3.5 Hydroboration 161
6.3.6 Oxidation 163
6.3.7 Esterification, transesterification and acetylation 167
6.3.8 Other metal catalyzed carbon–carbon bond forming reactions 168
6.4 Fluorous Organocatalysis 174
References 177
7 Solid-Supported Catalysis 185
Michelle L. Richards and Peter J.H. Scott
7.1 Introduction 185
7.1.1 General Introduction 185
7.1.2 The impact of solid-phase organic synthesis on green chemistry 187
7.2 Immobilized Palladium Catalysts for Green Chemistry 188
7.2.1 Introduction 188
7.2.2 Suzuki reactions 189
7.2.3 Heck–Mizoroki reactions in water 193
7.2.4 Sonogashira reactions in water 194
7.2.5 Tsuji–Trost reactions in water 196
7.3 Immobilized Rhodium Catalysts for Green Chemistry 197
7.3.1 Introduction 197
7.3.2 Rhodium(II) carbenoid chemistry 197
7.3.3 Rhodium (I)-catalyzed conjugate addition reactions 198
7.3.4 Rhodium-catalyzed hydrogenation reactions 198
7.3.5 Rhodium-catalyzed carbonylation reactions 199
7.4 Immobilized Ruthenium Catalysts for Green Chemistry 199
7.4.1 Introduction 199
7.4.2 Ruthenium-catalyzed metathesis reactions 199
7.4.3 Ruthenium-catalyzed transfer hydrogenation 204
7.4.4 Ruthenium-catalyzed opening of epoxides 206
7.4.5 Ruthenium-catalyzed cyclopropanation reactions 206
7.4.6 Ruthenium-catalyzed halogenation reactions 207
7.5 Other Immobilized Catalysts for Green Chemistry 208
7.5.1 Immobilized cobalt catalysts 208
7.5.2 Immobilized copper catalysts 208
7.5.3 Immobilized iridium catalysts 209
7.6 Conclusions 210
References 210
8 Biocatalysis 217
Qi Wu and Junhua Tao
8.1 Introduction 217
8.2 Brief History of Biocatalysis 217
8.3 Biocatalysis Toolboxes 218
8.4 Enzymatic Synthesis of Pharmaceuticals 218
8.4.1 Synthesis of atorvastatin and rosuvastatin 219
8.4.2 Synthesis of b-lactam antibiotics 222
8.4.3 Synthesis of glycopeptides 225
8.4.4 Synthesis of tyrocidine antibiotics 227
8.4.5 Synthesis of polyketides 230
8.4.6 Synthesis of taxoids and epothilones 231
8.4.7 Synthesis of pregabalin 234
8.5 Summary 237
Acknowledgment 237
References 237
III GREEN SYNTHETIC TECHNIQUES 241
9 Green Solvents 243
Simon W. Breeden, James H. Clark, Duncan J. Macquarrie and James Sherwood
9.1 Introduction 243
9.2 Origins of the Neoteric Solvents 244
9.2.1 Ionic liquids 244
9.2.2 Supercritical carbon dioxide 245
9.2.3 Water 245
9.2.4 Perfluorinated solvents 246
9.2.5 Biosolvents 246
9.2.6 Petroleum solvents 247
9.3 Application of Green Solvents 248
9.3.1 Synthetic organic chemistry overview 248
9.3.2 Diels–Alder cycloaddition 248
9.3.3 Cross-coupling 250
9.3.4 Ring-closing metathesis 253
9.4 Recapitulation and Possible Future Developments 256
References 257
10 Organic Synthesis in Water 263
Marc-Olivier Simon and Chao-Jun Li
10.1 Introduction 263
10.2 Pericyclic Reactions 264
10.3 Passerini and Ugi Reactions 268
10.4 Nucleophilic Ring-Opening Reactions 269
10.5 Transition Metal Catalyzed Reactions 271
10.5.1 Pericyclic reactions 271
10.5.2 Addition reactions 273
10.5.3 Coupling reactions 274
10.5.4 Transition metal catalyzed reactions of carbenes 279
10.5.5 Oxidations and reductions 280
10.6 Organocatalytic Reactions 283
10.6.1 Aldol reaction 283
10.6.2 Michael addition 284
10.6.3 Mannich reaction 285
10.6.4 Cycloaddition reactions 286
10.7 Miscellaneous 288
10.8 Conclusion 290
References 291
11 Solvent-Free Synthesis 297
James Mack and Sivaramakrishnan Muthukrishnan
11.1 Introduction 297
11.2 Alternative Methods to Solution Based Synthesis 300
11.2.1 Mortar and pestle 300
11.2.2 Ball milling 301
11.2.3 Microwave assisted solvent-free synthesis 309
References 318
12 Microwave Synthesis 325
Michael P. Pollastri and William G. Devine
12.1 Introduction 325
12.2 The Mechanism of Microwave Heating 326
12.3 The Green Properties of Microwave Heating 326
12.3.1 Green solvents 326
12.3.2 Energy reduction 328
12.3.3 Improved reaction outcomes resulting in less purification 328
12.4 Microwaves versus Green Chemistry Principles 329
12.5 Green Solvents in Microwave Chemistry 329
12.5.1 Water 329
12.5.2 Solventless reactions 330
12.5.3 Ionic liquids 331
12.5.4 Glycerol 332
12.6 Catalysis 333
12.6.1 Microwave assisted CH bond activation 333
12.6.2 Microwave assisted carbonylation reactions 334
12.7 Microwave Chemistry Scale-Up 334
12.7.1 Flow microwave reactors 335
12.7.2 Energy efficiency of large-scale microwave reactions 336
12.7.3 Large-scale batch microwave reactors 339
12.7.4 Future work in microwave scale-up 340
12.8 Summary 340
References 341
13 Ultrasonic Reactions 343
Rodrigo Cella and Helio A. Stefani
13.1 Introduction 343
13.2 How Does Cavitation Work? 344
13.3 Condensation Reactions 345
13.4 Michael Additions 348
13.5 Mannich Reactions 349
13.6 Heterocycles Synthesis 350
13.7 Coupling Reactions 353
13.8 Miscellaneous 358
13.9 Conclusions 359
References 359
14 Photochemical Synthesis 363
Stefano Protti, Maurizio Fagnoni and Angelo Albini
14.1 Introduction 363
14.2 Synthesis and Rearrangement of Open-Chain Compounds 365
14.3 Synthesis of Three- and Four-Membered Rings 370
14.3.1 Synthesis of three-membered rings 370
14.3.2 Synthesis of four-membered rings 372
14.4 Synthesis of Five-, Six (and Larger)-Membered Rings 378
14.4.1 Synthesis of five-membered rings 379
14.4.2 Synthesis of six-membered rings 381
14.4.3 Synthesis of larger rings 383
14.5 Oxygenation and Oxidation 385
14.6 Conclusions 387
Acknowledgment 388
References 388
15 Solid-Supported Organic Synthesis 393
Gorakh S. Yellol and Chung-Ming Sun
15.1 Introduction 393
15.2 Techniques of Solid-Supported Synthesis 394
15.2.1 General method of solid-supported synthesis 394
15.2.2 Supports for supported synthesis 395
15.2.3 Linkers for solid-supported synthesis 398
15.2.4 Reaction monitoring 401
15.2.5 Separation techniques 402
15.2.6 Automation technique 404
15.2.7 Split and combine (split and mix) technique 405
15.3 Solid-Supported Heterocyclic Chemistry 406
15.3.1 Multicomponent reaction 406
15.3.2 Combinatorial library synthesis 408
15.3.3 Diversity-oriented synthesis 412
15.3.4 Multistep parallel synthesis 412
15.4 Solid-Supported Natural Product Synthesis 417
15.4.1 Total synthesis of natural product 418
15.4.2 Synthesis of natural product-like libraries 420
15.4.3 Synthesis of natural product inspired compounds 421
15.5 Solid-Supported Synthesis of Peptides and Carbohydrates 422
15.5.1 Solid-supported synthesis of peptides 422
15.5.2 Solid-supported synthesis of carbohydrates 424
15.6 Soluble-Supported Synthesis 426
15.6.1 Poly(ethylene glycol) 426
15.6.2 Linear polystyrene (LPS) 427
15.6.3 Ionic liquids 428
15.7 Multidisciplinary Synthetic Approaches 429
15.7.1 Solid-supported synthesis and microwave synthesis 429
15.7.2 Solid-supported synthesis under sonication 431
15.7.3 Solid-supported synthesis in green media 433
15.7.4 Solid-supported synthesis and photochemical reactions 433
References 434
16 Fluorous Synthesis 443
Wei Zhang
16.1 Introduction 443
16.2 “Heavy” versus “Light” Fluorous Chemistry 443
16.3 Green Aspects of Fluorous Techniques 444
16.3.1 Fluorous solid-phase extraction to reduce the amount of
waste solvent 444
16.3.2 Recycling techniques in fluorous synthesis 444
16.3.3 Monitoring fluorous reactions 446
16.3.4 Two-in-one strategy for using fluorous linkers 448
16.3.5 Efficient microwave-assisted fluorous synthesis 448
16.3.6 Atom economic fluorous multicomponent reactions 451
16.3.7 Fluorous reactions and separations in aqueous media 451
16.4 Fluorous Techniques for Discovery Chemistry 451
16.4.1 Fluorous ligands for metal catalysis 451
16.4.2 Fluorous organocatalysts for asymmetric synthesis 451
16.4.3 Fluorous reagents 453
16.4.4 Fluorous scavengers 454
16.4.5 Fluorous linkers 454
16.5 Conclusions 465
References 465
17 Reactions in Ionic Liquids 469
Hui Wang, Xiaosi Zhou, Gabriela Gurau and Robin D. Rogers
17.1 Introduction 469
17.2 Finding the Right Role for ILs in the Pharmaceutical Industry 470
17.2.1 Use of ILs as solvents in the synthesis of drugs or drug intermediates 470
17.2.2 Use of ILs for pharmaceutical crystallization 472
17.2.3 Use of ILs in pharmaceutical separations 472
17.2.4 Use of ILs for the extraction of drugs from natural products 476
17.2.5 Use of ILs for drug delivery 477
17.2.6 Use of ILs for drug detection 478
17.2.7 ILs as pharmaceutical ingredients 479
17.3 Conclusions and Prospects 489
References 490
18 Multicomponent Reactions 497
Yijun Huang, Ahmed Yazbak and Alexander D€omling
18.1 Introduction 497
18.2 Multicomponent Reactions in Aqueous Medium 498
18.2.1 Multicomponent reactions are accelerated in water 498
18.2.2 Multicomponent reactions “on water” 500
18.3 Solventless Multicomponent Reactions 503
18.4 Case Studies of Multicomponent Reactions in Drug Synthesis 507
18.4.1 Schistosomiasis drug praziquantel 507
18.4.2 Schizophrenia drug olanzapine 509
18.4.3 Oxytocin antagonist GSK221149A 510
18.4.4 Miscellaneous 511
18.5 Perspectives of Multicomponent Reactions in Green Chemistry 512
18.5.1 The union of multicomponent reactions 512
18.5.2 Sustainable synthesis technology by multicomponent reactions 515
18.5.3 Alternative solvents for green chemistry 516
18.6 Outlook 518
References 518
19 Flow Chemistry 523
Frederic G. Buono, Michael A. Gonzalez and Jale M€uslehiddinoglu
19.1 Introduction 523
19.2 Types of Flow Reactors 525
19.2.1 Microreactors 526
19.2.2 Miniaturized tubular reactors 527
19.2.3 Spinning Disk Reactor (SDR) 528
19.2.4 Spinning tube-in-tube reactor 530
19.2.5 Heat exchanger reactors 531
19.3 Application of Flow Reactors 532
19.3.1 Prevention of waste and yield improvement 532
19.3.2 Increase energy efficiency and minimize potential
for accidents 535
19.3.3 Use of heterogeneous catalysts and atom efficiency 540
19.3.4 Use of supported reagents 543
19.3.5 Photochemistry 543
19.4 Conclusion 544
Acknowledgment 544
References 545
20 Green Chemistry Strategies for Medicinal Chemists 551
Berkeley W. Cue Jr.
20.1 Introduction 551
20.2 Historical Background: The Evolution of Green Chemistry
in the Pharmaceutical Industry 552
20.3 Green Chemistry in Process Chemistry, Manufacturing and
Medicinal Chemistry and Barriers to Rapid Uptake 553
20.4 Green Chemistry Activity Among PhRMA
Member Companies 554
20.5 Modeling Waste Generation in Pharmaceutical R&D 555
20.6 Strategies to Reduce the Use of Solvents 556
20.7 Green Reactions for Medicinal Chemistry 558
20.8 Modeling Waste Co-Produced During R&D Synthesis 560
20.9 Green Chemistry and Drug Design: Benign by Design 562
20.10 Green Biology 565
20.11 Conclusions and Recommendations 565
References 567
IV GREEN TECHNIQUES FOR MEDICINAL CHEMISTRY 571
21 The Business of Green Chemistry in the Pharmaceutical Industry 573
Andrea Larson and Mark Meier
21.1 Introduction 573
21.2 Green Chemistry as a Business Opportunity 574
21.3 The Need for Green Chemistry 574
21.4 The Business Case for Green Chemistry Principles 576
21.5 An Idea whose Time Has Arrived 579
21.6 What Green Chemistry Is and What It Is Not 582
21.7 Overcoming Obstacles to Green Chemistry 583
21.8 Conclusion 586
References 586
22 Preparative Chromatography 589
Kathleen Mihlbachler and Olivier Dapremont
22.1 Introduction 589
22.2 Preparative Chromatography for Intermediates and APIs 590
22.2.1 Early discovery 590
22.2.2 Clinical and commercial scale quantities 590
22.2.3 Chiral separations 591
22.3 Chromatography and the 12 Principles of Green Chemistry 592
22.3.1 The 12 principles 592
22.3.2 The metrics 593
22.3.3 The impact of chromatography on the environment 594
22.4 Overview of Chromatography Systems 595
22.4.1 Chromatographic separation mechanisms 595
22.4.2 Elution modes: isocratic versus gradient 596
22.4.3 Batch chromatography 596
22.4.4 Continuous chromatography 598
22.4.5 Supercritical fluid chromatography 600
22.4.6 Solvent Recycling 601
22.5 Examples of Process Chromatography 602
22.5.1 Early process development 602
22.5.2 Implementation of SMB technology for chiral resolution 603
22.5.3 Global process optimization: combining synthesis and
impurity removal 605
22.5.4 Chromatography versus crystallization to remove a genotoxic impurity 607
22.5.5 SMB mining – recover product from waste stream 608
22.6 Conclusions 609
References 610
23 Green Drug-Delivery Formulations 613
Scott B. McCray and David K. Lyon
23.1 Introduction and Summary 613
23.2 Application of Green Chemistry in the Pharmaceutical Industry 614
23.3 Need for Green Chemistry Technologies to Deliver Low-Solubility Drugs 615
23.3.1 The need 615
23.3.2 Characteristics of low-solubility drugs 616
23.3.3 Low bioavailability 616
23.4 SDD Drug-Delivery Platform 617
23.4.1 Technology overview 617
23.4.2 Polymer choice 619
23.4.3 Process description 620
23.4.4 Formulation description 622
23.4.5 Dissolved drug 622
23.4.6 Drug in colloids and micelles 623
23.4.7 SDD efficacy 623
23.4.8 In Vitro testing 624
23.4.9 In Vivo testing 624
23.5 Green Chemistry Advantages of SDD Drug-Delivery Platform 625
23.5.1 Modeling 625
23.5.2 Reduction in waste due to efficient screening 626
23.5.3 Reduction of waste during manufacturing 626
23.5.4 Reduction in waste due to nonprogression of candidates 627
23.5.5 Reduction in waste due to lower dose requirements 627
23.5.6 Reduction in amount of drug that enters the environment 627
23.5.7 Calculated impact on waste reduction 627
23.6 Conclusions 628
23.7 Acknowledgments 628
References 628
24 Green Process Chemistry in the Pharmaceutical Industry: Recent Case Studies 631
Ji Zhang and Berkeley W. Cue Jr
24.1 Introduction 631
24.2 Sitagliptin: From Green to Greener; from a Catalytic Reaction to a
Metal-Free Enzymatic Process 632
24.3 Saxagliptin: Elimination of Toxic Chemicals and the Use of a Biocatalytic Approach 637
24.4 Armodafinil: From Classical Resolution to Catalytic Asymmetric
Oxidation to Maximize the Output 639
24.5 Emend: Elimination of the Use of Tebbe Reagent for Pollution Prevention
and Utilization of Catalytic Asymmetric Transfer Hydrogenation 642
24.6 Greening a Process via One-pot or Telescoped Processing 646
24.7 Greening a Process via Salt Formation 651
24.8 Metal-free Organocatalysis: Applications of Chiral
Phase-transfer Catalysis 652
24.9 Conclusions 653
References 657
25 Green Analytical Chemistry 659
Paul Ferguson, Mark Harding and Jennifer Young
25.1 Introduction 659
25.2 Method Assessment 660
25.3 Solvents and Additives for pH Adjustment 661
25.4 Sample Preparation 665
25.5 Techniques and Methods 666
25.5.1 Screening methods 666
25.5.2 Liquid chromatography 667
25.5.3 Gas chromatography 676
25.5.4 Supercritical fluid chromatography 678
25.5.5 Chiral analysis 679
25.5.6 Process analytical technology 680
25.6 Conclusions 681
Acknowledgments 682
References 682
26 Green Chemistry for Tropical Disease 685
Joseph M.D. Fortunak, David H. Brown Ripin and David S. Teager
26.1 Introduction 685
26.2 Interventions in Drug Dosing 686
26.2.1 Dose reduction through innovative drug formulation 686
26.2.2 Dose optimization: green dose setting 687
26.3 Active Pharmaceutical Ingredient Cost Reduction with Green Chemistry 688
26.3.1 Revision of the original manufacturing process 688
26.3.2 Case studies: manufacture of drugs for AntiRetroviral therapy 689
26.3.3 Case studies: Artemisinin combination therapies for malaria treatment 695
26.4 Conclusions 698
References 698
27 Green Engineering in the Pharmaceutical Industry 701
Concepcion Jimenez- Gonzalez, Celia S. Ponder, Robert E. Hannah and James R. Hagan
27.1 Introduction 701
27.2 Green Engineering Principles 702
27.2.1 Optimizing the use of resources 702
27.2.2 Life cycle thinking 706
27.2.3 Minimizing environment, health and safety hazards by design 709
27.3 More Challenge Areas for Sustainability in the Pharmaceutical Industry 709
27.4 Future Outlook and Challenges 712
References 712
Index
English
“In summary, the book covers new advances in green chemistry, which are applied in the pharmaceutical industry. It also shows ways of introducing innovation in a more holistic manner, through the development of smart equipment, techniques, or innovative chemicals.” (Green Processing and Synthesis, 1 August 2012)
