Chemistry for Pharmacy Students General, Organic and Natural Product Chemistry

Introduces the key areas of chemistry required for all pharmacy degree courses and focuses on the properties and actions of drug molecules

This new edition provides a clear and comprehensive overview of the various areas of general, organic, and natural products chemistry (in relation to drug molecules). Structured to enhance student understanding, it places great emphasis on the applications of key theoretical aspects of chemistry required by all pharmacy and pharmaceutical science students. This second edition particularly caters for the chemistry requirements in any ‘Integrated Pharmacy Curricula’, where science in general is meant to be taught ‘not in isolation’, but together with, and as a part of, other practice and clinical elements of the course.

Chemistry for Pharmacy Students: General, Organic and Natural Product Chemistry, 2nd Edition is divided into eight chapters. It opens with an overview of the general aspects of chemistry and their importance to modern life, with emphasis on medicinal applications. The text then moves on to discuss the concepts of atomic structure and bonding and the fundamentals of stereochemistry and their significance to pharmacy in relation to drug action and toxicity. Various aspects of organic functional groups, organic reactions, heterocyclic chemistry, nucleic acids and their pharmaceutical importance are then covered in subsequent chapters, with the final chapter dealing with drug discovery and development, and natural product chemistry.

• Provides a student-friendly introduction to the main areas of chemistry required by pharmacy degree courses
• Written at a level suitable for non-chemistry students in pharmacy, but also relevant to those in life sciences, food science, and the health sciences
• Includes learning objectives at the beginning of each chapter
• Focuses on the physical properties and actions of drug molecules

Chemistry for Pharmacy Students: General, Organic and Natural Product Chemistry, 2nd Edition is an essential book for pharmacy undergraduate students, and a helpful resource for those studying other subject areas within pharmaceutical sciences, biomedical sciences, cosmetic science, food sciences, and health and life sciences.

Lutfun Nahar, BSc (Hons), PhD, MRSC, FHEA, is an Honorary Lecturer, and actively involved in research at the Faculty of Science at Liverpool John Moores University, UK. She has published well over 350 peer-reviewed scientific papers, invited reviews, abstracts, books, and book chapters in the areas of Synthetic Organic Medicinal and Natural Products Chemistry. She is the Managing Editor of the Wiley journal, Phytochemical Analysis. Her scientific profile has been published in every edition of the Marquis "Who's Who in the World" since 2009, and "Who's Who in Science and Engineering" since 2010.

Satyajit Sarker BPharm (Hons), MPharm, PhD, FHEA, is a Professor of Pharmacy, and the Director of School of Pharmacy and Biomolecular Sciences at Liverpool John Moores University, UK. He is the President of the Phytochemical Society of Europe, and the Editor-in-Chief of the Wiley journal, Phytochemical Analysis. He has over 520 publications to his credit. His scientific profile has been published in every edition of the Marquis "Who's Who in the World" since 2010.

Preface to the second edition xv

Preface to the first edition xvii

Chapter 1: Introduction 1

1.1 Role of Chemistry in Modern Life 1

1.2 Solutions and Concentrations 4

1.3 Suspension, Colloid and Emulsion 6

1.4 Electrolytes, Nonelectrolytes and Zwitterions 7

1.5 Osmosis and Tonicity 8

1.6 Physical Properties of Drug Molecules 10

1.6.1 Physical State 10

1.6.2 Melting Point and Boiling Point 10

1.6.3 Polarity and Solubility 11

1.7 Acid–Base Properties and pH 13

1.7.1 Acid–Base Definitions 14

1.7.2 Electronegativity and Acidity 18

1.7.3 Acid–Base Properties of Organic Functional Groups 19

1.7.4 pH, pOH and pK_a Values 22

1.7.5 Acid–Base Titration: Neutralization 30

1.8 Buffer and its Use 32

1.8.1 Common Ion Effects and Buffer Capacity 34

Chapter 2: Atomic Structure and Bonding 37

2.1 Atoms, Elements and Compounds 37

2.2 Atomic Structure: Orbitals and Electronic Configurations 39

2.3 Chemical Bonding Theories: Formation of Chemical Bonds 43

2.3.1 Lewis Structures 43

2.3.2 Resonance and Resonance Structures 47

2.3.3 Electronegativity and Chemical Bonding 48

2.3.4 Various Types of Chemical Bonding 49

2.4 Bond Polarity and Intermolecular Forces 54

2.4.1 Dipole–Dipole Interactions 54

2.4.2 van der Waals Forces 55

2.4.3 Hydrogen Bonding 56

2.5 Hydrophilicity and Lipophilicity 57

2.6 Significance of Chemical Bonding in Drug–Receptor Interactions 60

2.7 Significance of Chemical Bonding in Protein–Protein Interactions 63

2.8 Significance of Chemical Bonding in Protein–DNA Interactions 63

Chapter 3: Stereochemistry 65

3.1 Stereochemistry: Definition 66

3.2 Isomerism 66

3.2.1 Constitutional Isomers 66

3.2.2 Stereoisomers 67

3.3 Stereoisomerism of Molecules with More than One Stereocentre 82

3.3.1 Diastereomers and Meso Structures 82

3.3.2 Cyclic Compounds 84

3.3.3 Geometrical Isomers of Alkenes and Cyclic Compounds 85

3.4 Significance of Stereoisomerism in Determining Drug Action and Toxicity 88

3.5 Synthesis of Chiral Molecules 91

3.5.1 Racemic Forms 91

3.5.2 Enantioselective Synthesis 92

3.6 Separation of Stereoisomers: Resolution of Racemic Mixtures 93

3.7 Compounds with Stereocentres Other than Carbon 94

3.8 Chiral Compounds that Do Not Have Four Different Groups 94

Chapter 4: Organic Functional Groups 97

4.1 Organic Functional Groups: Definition and Structural Features 97

4.2 Hydrocarbons 100

4.3 Alkanes, Cycloalkanes and Their Derivatives 100

4.3.1 Alkanes 100

4.3.2 Cycloalkanes 108

4.3.3 Alkyl Halides 111

4.3.4 Alcohols 119

4.3.5 Ethers 125

4.3.6 Thiols 129

4.3.7 Thioethers 131

4.3.8 Amines 134

4.4 Carbonyl Compounds 140

4.4.1 Aldehydes and Ketones 140

4.4.2 Carboxylic acids 148

4.4.3 Acid Chlorides 154

4.4.4 Acid Anhydrides 155

4.4.5 Esters 157

4.4.6 Amides 160

4.4.7 Nitriles 163

4.5 Alkenes and their Derivatives 164

4.5.1 Nomenclature of Alkenes 165

4.5.2 Physical Properties of Alkenes 166

4.5.3 Structure of Alkenes 167

4.5.4 Industrial uses of Alkenes 167

4.5.5 Preparations of Alkenes 168

4.5.6 Reactivity and Stability of Alkenes 168

4.5.7 Reactions of Alkenes 169

4.6 Alkynes and their Derivatives 169

4.6.1 Nomenclature of Alkynes 170

4.6.2 Structure of Alkynes 170

4.6.3 Acidity of Terminal Alkynes 171

4.6.4 Heavy Metal Acetylides: Test for Terminal Alkynes 171

4.6.5 Industrial Uses of Alkynes 172

4.6.6 Preparations of Alkynes 172

4.6.7 Reactions of Alkynes 172

4.6.8 Reactions of Metal Alkynides 174

4.7 Aromatic Compounds and their Derivatives 174

4.7.1 History 175

4.7.2 Definition: Hückel’s Rule 175

4.7.3 General Properties of Aromatic Compounds 175

4.7.4 Classification of Aromatic Compounds 176

4.7.5 Pharmaceutical importance of Aromatic Compounds: Some Examples 177

4.7.6 Structure of Benzene: Kekulé Structure of Benzene 179

4.7.7 Nomenclature of Benzene Derivatives 183

4.7.8 Electrophilic Substitution of Benzene 184

4.7.9 Alkylbenzene: Toluene 190

4.7.10 Phenols 192

4.7.11 Aromatic Amines: Aniline 199

4.7.12 Polycyclic Benzenoids 207

4.8 Importance of Functional Groups in Determining Drug Actions and Toxicity 209

4.8.1 Structure-Activity Relationships of Sulpha Drugs 210

4.8.2 Structure-Activity Relationships of Penicillins 211

4.8.3 Paracetamol Toxicity 213

4.9 Importance of Functional Groups in Determining Stability of Drugs 213

Chapter 5: Organic Reactions 215

5.1 Types of Organic Reactions Occur with Functional Groups 215

5.2 Reaction Mechanisms and Types of Arrow in Chemical Reactions 216

5.3 Free Radical Reactions: Chain Reactions 217

5.3.1 Free Radical Chain Reaction of Alkanes 217

5.3.2 Relative Stabilities of Carbocations, Carbanions, Radicals and Carbenes 219

5.3.3 Allylic Bromination 221

5.3.4 Radical Inhibitors 222

5.4 Addition Reactions 223

5.4.1 Electrophilic Additions to Alkenes and Alkynes 223

5.4.2 Symmetrical and Unsymmetrical Addition to Alkenes and Alkynes 226

5.4.3 Nucleophilic Addition to Aldehydes and Ketones 240

5.5 Elimination Reactions: 1,2-Elimination or β-Elimination 254

5.5.1 E1 Reaction or First Order Elimination 255

5.5.2 E2 Reaction or Second Order Elimination 256

5.5.3 Dehydration of Alcohols 257

5.5.4 Dehydration of Diols: Pinacol Rearrangement 259

5.5.5 Base-Catalysed Dehydrohalogenation of Alkyl Halides 260

5.6 Substitution Reactions 265

5.6.1 Nucleophilic Substitutions 266

5.6.2 Nucleophilic Substitutions of Alkyl Halides 273

5.6.3 Nucleophilic Substitutions of Alcohols 276

5.6.4 Nucleophilic Substitutions of Ethers and Epoxides 282

5.6.5 Nucleophilic Acyl Substitutions of Carboxylic Acid Derivatives 286

5.6.6 Substitution Versus Elimination 293

5.7 Electrophilic Substitutions 294

5.7.1 Electrophilic Substitution of Benzene 294

5.8 Hydrolysis 300

5.8.1 Hydrolysis of Carboxylic Acid Derivatives 300

5.9 Oxidation–Reduction Reactions 305

5.9.1 Oxidizing and Reducing Agents 305

5.9.2 Oxidation of Alkenes 305

5.9.3 Oxidation of Alkynes 307

5.9.4 Hydroxylation of Alkenes 307

5.9.5 Oxidative Cleavage of syn-Diols 308

5.9.6 Ozonolysis of Alkenes 308

5.9.7 Ozonolysis of Alkynes 309

5.9.8 Oxidation of Alcohols 309

5.9.9 Oxidation of Aldehydes and Ketones 311

5.9.10 Baeyer–Villiger Oxidation of Aldehydes or Ketones 312

5.9.11 Reduction of Alkyl Halides 312

5.9.12 Reduction of Organometallics 312

5.9.13 Reduction of Alcohols via Tosylates 313

5.9.14 Reduction of Aldehydes and Ketones 313

5.9.15 Clemmensen Reduction 315

5.9.16 Wolff–Kishner Reduction 316

5.9.17 Reduction of Acid Chlorides 316

5.9.18 Reduction of Esters 317

5.9.19 Hydride Reduction of Carboxylic Acids 318

5.9.20 Reduction of Oximes or Imine Derivatives 318

5.9.21 Reduction of Amides, Azides and Nitriles 319

5.9.22 Reductive Amination of Aldehydes and Ketones 320

5.10 Pericyclic Reactions 320

5.10.1 Diels–Alder Reaction 320

5.10.2 Essential Structural Features for Dienes and Dienophiles 321

5.10.3 Stereochemistry of the Diels–Alder Reaction 322

5.10.4 Sigmatropic Rearrangements 323

5.10.5 Hydrogen Shift 323

5.10.6 Alkyl Shift: Cope Rearrangement 324

5.10.7 Claisen Rearrangement 324

Chapter 6: Heterocyclic Compounds 327

6.1 Heterocyclic Compounds and their Derivatives 327

6.1.1 Medicinal Importance of Heterocyclic Compounds 328

6.1.2 Nomenclature of Heterocyclic Compounds 329

6.1.3 Physical Properties of Heterocyclic Compounds 331

6.2 Pyrrole, Furan and Thiophene: Unsaturated Heterocycles 332

6.2.1 Physical Properties of Pyrrole, Furan and Thiophene 333

6.2.2 Preparations of Pyrrole, Furan and Thiophene 333

6.2.3 Reactions of Pyrrole, Furan and Thiophene 335

6.3 Pyridine 339

6.3.1 Physical Properties of Pyridine 339

6.3.2 Preparations of Pyridine 340

6.3.3 Reactions of Pyridine 340

6.4 Oxazole, Imidazole and Thiazole 342

6.4.1 Physical Properties of Oxazole, Imidazole and Thiazole 343

6.4.2 Preparations of Oxazole, Imidazole and Thiazole 344

6.4.3 Reactions of Oxazole, Imidazole and Thiazole 345

6.5 Isoxazole, Pyrazole and Isothiazole 346

6.5.1 Physical Properties of Isoxazole, Pyrazole and Isothiazole 348

6.5.2 Preparations of Isoxazole, Pyrazole and Isothiazole 348

6.5.3 Reactions of Isoxazole, Pyrazole and Isothiazole 348

6.6 Pyrimidine 349

6.6.1 Physical Properties of Pyrimidine 350

6.6.2 Preparations of Pyrimidine 350

6.6.3 Reactions of Pyrimidine 351

6.7 Purine 352

6.7.1 Physical Properties of Purine 353

6.7.2 Preparations of Purine 353

6.7.3 Reactions of Purine 353

6.8 Quinoline and Isoquinoline 354

6.8.1 Physical Properties of Quinoline and Isoquinoline 354

6.8.2 Preparations of Quinoline and Isoquinoline 355

6.8.3 Reactions of Quinoline and Isoquinoline 357

6.9 Indole 358

6.9.1 Physical Properties of Indole 359

6.9.2 Preparations of Indole 359

6.9.3 Reactions of Indole 360

6.9.4 Test for Indole 361

Chapter 7: Nucleic Acids 363

7.1 Nucleic Acids 363

7.1.1 Synthesis of Nucleosides and Nucleotides 365

7.1.2 Structure of Nucleic Acids 366

7.1.3 Nucleic Acids and Heredity 370

7.1.4 DNA Fingerprinting 373

7.2 Amino Acids and Peptides 373

7.2.1 Fundamental Structural Features of an Amino acid 376

7.2.2 Essential Amino Acids 376

7.2.3 Glucogenic and Ketogenic Amino Acids 377

7.2.4 Amino Acids in Human Body 377

7.2.5 Acid–Base Properties of Amino Acids 378

7.2.6 Isoelectric Points of Amino Acids and Peptides 378

Chapter 8: Natural Product Chemistry 381

8.1 Introduction to Natural Products 381

8.1.1 Natural Products 381

8.1.2 Natural Products in Medicine 382

8.1.3 Drug Discovery and Natural Products 385

8.2 Alkaloids 390

8.2.1 Properties of Alkaloids 391

8.2.2 Classification of Alkaloids 391

8.2.3 Tests for Alkaloids 410

8.3 Carbohydrates 410

8.3.1 Classification of Carbohydrates 411

8.3.2 Stereochemistry of Sugars 414

8.3.3 Cyclic Structures of Monosaccharides 415

8.3.4 Acetal and Ketal Formation in Sugars 416

8.3.5 Oxidation, Reduction, Esterification and Etherification of Monosaccharides 417

8.3.6 Pharmaceutical Uses of Monosaccharides 420

8.3.7 Disaccharides 420

8.3.8 Polysaccharides 423

8.3.9 Miscellaneous Carbohydrates 426

8.3.10 Cell Surface Carbohydrates and Blood Groupings 428

8.4 Glycosides 429

8.4.1 Biosynthesis of Glycosides 430

8.4.2 Classification 430

8.4.3 Test for Hydrocyanic Acid (HCN) 432

8.4.4 Pharmaceutical Uses and Toxicity 432

8.4.5 Anthracene/Anthraquinone Glycosides 433

8.4.6 Isoprenoid Glycosides 436

8.4.7 Iridoid and Secoiridoid Glycosides 440

8.5 Terpenoids 442

8.5.1 Classification 442

8.5.2 Biosynthesis of Terpenoids 443

8.5.3 Monoterpenes 445

8.5.4 Sesquiterpenes 446

8.5.5 Diterpenes 455

8.5.6 Triterpenes 461

8.5.7 Tetraterpenes 465

8.6 Steroids 466

8.6.1 Structures of Steroids 467

8.6.2 Stereochemistry of Steroids 468

8.6.3 Physical Properties of Steroids 468

8.6.4 Types of Steroid 469

8.6.5 Biosynthesis of Steroids 471

8.6.6 Synthetic Steroids 472

8.6.7 Functions of Steroids 473

8.7 Phenolics 476

8.7.1 Phenylpropanoids 477

8.7.2 Coumarins 478

8.7.3 Flavonoids and Isoflavonoids 481

8.7.4 Lignans 486

8.7.5 Tannins 489

Index 493

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