Pharmaceutical Chemistry of Natural Products

Contents

Preface v

Acknowledgements vii

Chapter 1 Introduction to Pharmaceutical Chemistry of Natural Products 1

_ Introduction 1

_ Drug Discovery from Natural Products 2

_ Nomenclature 3

_ Classifi cation of Natural Products 3

_ Identifi cation of Natural Products 6

_ Techniques Involved in Natural Product Lead Discovery 6

_ Natural Products as Pharmacological Tools 8

Chapter 2 Carbohydrates 11

_ Introduction 11

_ Classifi cation of Carbohydrates 12

_ Qualitative Chemical Tests for Carbohydrates 14

_ Monosaccharides 16

_ Confi guration of Monosaccharides 16

_ Ascending and Descending in Monosaccharides 18

_ Chemical Reactions of Monosaccharides 20

_ Ring Size of Monosaccharides 27

_ Ring structure of aldoses (glucose) 28

_ Ring structure of ketoses (fructose) 39

_ Conformations of Monosaccharides 42

_ Monosaccharides of Pharmaceutical Importance 42

_ Glucose 42

_ Fructose 44

_ Disaccharides 47

_ Biological Importance of Disaccharides 47

_ Classifi cation and Nomenclature of Disaccharides 47

_ Determination of the Structure of Disaccharides 49

_ Disaccharides of Pharmaceutical Importance 49

_ Sucrose 49

_ Lactose 53

_ Maltose 55

_ Trehalose 58

_ Trisaccharides 60

_ Gentianose 60

_ Tetrasaccharides 61

_ Stachyose 61

_ Polysaccharides 62

_ Classifi cation and Nomenclature of Polysaccharides 62

_ Polysaccharides of Pharmaceutical Importance 63

_ Starch 63

Chapter 3 Glycosides 73

_ Introduction 73

_ Classifi cation of Glycosides 74

_ Qualitative Chemical Tests for Glycosides 80

_ Isolation of Glycosides 81

_ Structural Determination of Glycosides 82

_ Glycosides of Pharmaceutical Importance 83

_ Salicin 83

_ Ruberythric acid 84

_ Arbutin 86

_ Sinigrin 88

_ Amygdalin 89

Chapter 4 Amino Acids, Peptides and Proteins 93

_ Amino Acids 93

_ Nomenclature of Amino Acids 94

_ Qualitative Chemical Tests for Amino Acids 94

_ Classifi cation of Amino Acids 95

_ Isolation and Separation of Amino Acids from Proteins 96

_ Synthesis of Amino Acids 97

_ General Physical and Chemical Properties of Amino Acids 102

_ Peptides 110

_ Classifi cation of Peptides 111

_ Synthesis of Peptides 111

_ General Principles of Peptide Synthesis 112

_ General Methods of Peptide Synthesis 115

_ Structure of Peptides 117

_ N-Terminal (Amino-end) degradation 118

_ C-Terminal (Carboxyl-end) degradation 120

_ Proteins 122

_ Biological Functions 122

_ Classifi cation of Proteins 122

_ Qualitative Chemical Tests for Proteins 124

_ Structure of Proteins 125

_ Proteins of Pharmaceutical Importance 132

_ Glutathione 132

_ Oxytocin 135

_ Thyroxine 138

_ Insulin 142

Chapter 5 Alkaloids 149

_ Introduction 149

_ Nomenclature of Alkaloids 150

_ Classifi cation of Alkaloids 150

_ Qualitative Chemical Tests for Alkaloids 158

_ Isolation or Production of Alkaloids 159

_ Determination of Molecular Structure of Alkaloids: General Methods 160

_ Molecular Formula Determination 160

_ Hydrolysis 160

_ Determination of Unsaturation 160

_ Functional Group Determination 160

_ Degradation of Alkaloids 164

_ Physical Methods in Conjunction with Chemical Methods 169

_ Synthesis 170

_ Alkaloids of Pharmaceutical Importance 170

_ Atropine 172

_ Morphine 177

_ Quinine 186

_ Papaverine 194

_ Emetine 199

_ Ephedrine 205

_ Ergotamine 207

_ Reserpine 214

_ Strychnine 222

_ Colchicine 232

_ Piperine 238

_ Nicotine 240

Chapter 6 Steroids and Hormones 249

_ Steroids 249

_ Nomenclature of Steroids 251

_ Stereochemistry 253

_ Qualitative Chemical Tests for Steroids 254

_ Sterols 254

_ Cholesterol 255

_ Lanosterol 256

_ Stigmasterol 257

_ Ergosterol 257

_ Miscellaneous Sterols 258

_ Structural Elucidation of Cholesterol 258

_ Bile acids 268

_ 5β-Cholanic Acid 270

_ 5α-Cholanic Acid 271

_ Functions of Bile Acids 271

_ Saponins and Sapogenins 272

_ Steroidal Saponins 272

_ Synthesis of Diosgenin 274

_ Pentacyclic Triterpenoid Saponins 276

_ Steroidal Alkaloids 277

_ Cardiac Steroids or Cardiotonic Glycosides 278

_ Hormones 282

_ Classifi cation 283

_ Sex Hormones 283

_ Biosynthesis of Sex Steroid Hormones 284

_ Androgens (Male Sex Hormones) 285

_ Biological Activities of Androgens 285

_ Therapeutic Uses of Anabolic Androgenic Steroids 286

_ Androgens of Pharmaceutical Importance 286

_ Androgesterone 286

_ Dehydroepiandrosterone 288

_ Testosterone 289

_ Methyl Testosterone 292

_ Fluoxymesterone 292

_ SAR of Androgens 293

_ Oestrogens 295

_ Isolation of Oestrogens 296

_ Biological Activities of Oestrogens 296

_ Metabolism of Oestrogens 297

_ Therapeutic Uses of Oestrogens 297

_ Classifi cation of Oestrogens 298

_ Oestrogens of Pharmaceutical Importance 300

_ Oestrone 300

_ Oestriol 301

_ Oestradiol 303

_ 17α-Ethinyloestradiol 305

_ Chemical Relationship Between Oestrone, Oestriol and Oestradiol 306

_ Nonsteroidal Oestrogens or Artifi cial Hormones 308

_ Stilboesterol 308

_ Hexoestrol 310

_ Dienoestrol 310

_ Benzoestrol 312

_ Structure–Activity Relationship (SAR) of Oestrogens 313

_ Corpus Luteum Hormones or Gestogens or Progestins 315

_ Metabolism of Progesterone 316

_ Biological Activities of Progestins 316

_ Therapeutic Uses of Progestins 316

_ Classifi cation of Progesterones 317

_ Progestins of Pharmaceutical Importance 318

_ Progesterone 318

_ Progesterone derivatives 322

_ Structure–Activity Relationship (SAR) of Progesterones 324

_ Hormonal Contraceptives 326

_ Oral Contraceptives 326

_ Corticosteroids (Adrenal Cortical Hormones) 327

_ Biological Effects of Glucocorticoids 327

_ Biosynthesis of the Adrenocorticoids from Cholesterol 328

_ Therapeutic Uses of Glucocorticoids 329

_ Classifi cation of Corticosteroids 329

_ Corticosteroids of Pharmaceutical Importance 333

_ Cortisone 333

_ Cortisol (or) Hydrocortisone 334

_ Aldosterone 337

_ Prednisolone 338

_ Dexamethasone 340

_ SAR of Corticosteroids 341

Chapter 7 Terpenoids

349

_ Introduction 349

_ Isolation of Terpenoids 352

_ Classifi cation of Terpenoids 353

_ Isoprene Rule and Special Isoprene Rule 361

_ General Methods for the Elucidation of Structure of Terpenoids 363

_ Hemiterpenoids 366

_ Monoterpenoids or Terpenes 367

_ Acyclic Monoterpenoids 367

_ Citral 367

_ Citronellal 371

_ Citronellol 373

_ Geraniol 374

_ Nerol 376

_ Linalool 377

_ Myrcene 378

_ Ocimene 378

_ Lavundulol 378

_ Cyclization Reactions of Acyclic Monoterpenoids 379

_ Monocyclic Monoterpenoids 381

_ Limonene 381

_ α-Terpineol 384

_ 1,8-cineol 389

_ Menthol and Menthone 390

_ Pulegone 392

_ Carvone 393

_ Ionones 397

_ Bicyclic Monoterpenoids 399

_ α-Pinene 399

_ Camphor 404

_ Borneol and Isoborneol 409

_ Camphene 410

_ Fenchone 410

_ Sesquiterpenoids 410

_ Acyclic Sesquiterpenoids 410

_ Farnesol 411

_ Monocyclic Sesquiterpenoids 413

_ Zingiberene 414

_ Bicyclic Sesquiterpenoids 417

_ Cadinene 417

_ Miscellaneous Sesquiterpenoids 418

_ Artimisinin 418

_ Gossypol and related compounds 418

_ Diterpenoids 419

_ Phytol 419

_ Vitamin A 419

_ Abietic Acid 420

_ Ginkolides 420

_ Taxol 420

_ Triterpenoids 421

_ Squalene 421

_ Lanosterol and Euphol 422

_ Amyrins 422

_ Tetraterpenoids 422

_ Polyterpenoids 423

Chapter 8 Flavonoids 427

_ Introduction 427

_ Isolation of Flavones 428

_ Structural Elucidation of Flavones 429

_ Flavonol 431

_ Structural Elucidation of Flavonol 432

_ Quercetin 434

_ Structural Elucidation of Quercetin 434

_ Isofl avones 437

_ Structural Elucidation of Isofl avones 438

Chapter 9 Vitamins 441

_ Introduction 441

_ Nomenclature of Vitamins 442

_ Classifi cation of Vitamins 443

_ Sources of Vitamins and Their Defi ciency Diseases 445

_ Vitamin A 446

_ Vitamin D 463

_ Vitamin E (Tocopherols) 474

_ Vitamin K 490

_ Vitamin B Complex 503

_ Vitamin B1 503

_ Vitamin B2 514

_ Vitamin B3 526

_ Vitamin B5 533

_ Vitamin B9 or Vitamin Bc or Folic Acid 540

_ Vitamin B6 or Pyridoxine 548

_ Vitamin B12 (Cyanocobalamin) 560

_ Vitamin C (Ascorbic Acid) 571

_ Vitamin-Like Compounds 588

_ PABA 588

_ Choline 588

_ Carnitine 589

_ Lipoic Acid or Vitamin Bt 590

Chapter 10 Antibiotics 593

_ Introduction 593

_ Historical Background 594

_ Spectrum of Activity of Chemotherapeutic Agents 594

_ Classifi cation Based on Mechanism of Action 596

_ Classifi cation Based on Chemical Structure 597

_ Penicillins 597

_ Introduction 597

_ Nomenclature 598

_ Production of Penicillins 598

_ Isolation of Penicillins 599

_ Chemical Degradation of Penicillins 600

_ Structural Elucidation of Penicillins 601

_ Classifi cation 606

_ Structure–Activity Relationship (SAR) of Penicillins 610

_ Cephalosporins 611

_ Introduction 611

_ Nomenclature 612

_ Degradation of Cephalosporins 613

_ Structural Elucidation of Cephalosporins 614

_ Classifi cation of Cephalosporins 619

_ Adverse Effects of Cephalosporins 623

_ Uses of Cephalosporins 623

_ SAR of Cephalosporins 623

_ Aminoglycoside antibiotics 625

_ Introduction 625

_ Production of Streptomycin 625

_ Isolation of Streptomycin 626

_ Streptomycin and Dihydrostreptomycin 626

_ Structural Elucidation of Streptomycin 627

_ Gentamycins 633

_ Neomycin 633

_ Kanamycin 634

_ Amikacin 635

_ Tobramycin 635

_ Netilmicin 636

_ SAR of Aminoglycoside Antibiotics 636

_ Tetracyclines 637

_ Introduction 637

_ Classifi cation of Tetracyclines 638

_ Structural Elucidation of Oxytetracycline 640

_ SAR of Tetracyclines 647

_ Chloramphenicol or Chloromycetin 649

_ Introduction 649

_ Structural Elucidation of Chloramphenicol 650

_ SAR of Chloramphenicol 653

_ Polypeptide antibiotics 654

_ Introduction 654

_ Bacitracin 654

_ Polymyxin 655

_ Lincomycins 655

Chapter 11 Purines, Pyrimidines and Nucleic Acids 659

_ Introduction 659

_ Purines 659

_ Classifi cation of Purines 660

_ Purine 661

_ Adenine 664

_ Guanine 666

_ Uric Acid 667

_ Xanthine 673

_ Methylxanthines 674

_ Caffeine 675

_ Theobromine 678

_ Theophylline 680

_ Hypoxanthine 682

_ Relationship Between Uric Acid and Xanthine Bases 683

_ Pyrimidines 684

_ Uracil 684

_ Thymine 686

_ Cytosine 687

_ 5-Methyl Cytosine 688

_ 5-Hydroxy Methyl Cytosine 689

_ NUCLEIC ACIDS 690

_ Classifi cation of Nucleic Acids 690

_ Functions of Nucleic Acids 691

_ Components of Nucleic Acids 691

_ Nucleosides 692

_ Nucleotides 694

_ Structural Elucidation of Nucleic Acids 696

_ Internucleotide Bond in RNA 713

_ Internucleotide Bond in DNA 714

_ Structure of DNA 715

_ Structure of RNA 719

_ Types of RNA 720

_ Differences Between DNA and RNA 722

Chapter 12 Enzymes

725

_ Introduction 725

_ Nomenclature and Classifi cation of Enzymes 726

_ Oxidoreductase 727

_ Transferase 727

_ Hydrolase 728

_ Lyase 728

_ Isomerase 728

_ Ligase 729

_ Qualitative Chemical Tests for Enzymes 729

_ Chemical Nature of Enzymes 730

_ Effi ciency of Enzymes 730

_ Specifi city of Enzymes 731

_ Stereospecifi city or Optical Specifi city 731

_ Reaction Specifi city 732

_ Substrate Specifi city 732

_ Theories of Enzyme Action 732

_ Lock and Key Model 733

_ Induced Fit Theory 733

_ Substrate Strain Theory 734

_ Mechanism of Enzyme Action 734

_ Coenzymes 735

_ Enzymatic Catalysis 738

_ Catalysis by Proximity and Orientation 738

_ Acid–Base Catalysis 738

_ Catalysis by Strain 739

_ Covalent Catalysis 739

_ Enzyme Inhibition 740

_ Reversible Inhibition 741

_ Irreversible Inhibition 743

Chapter 13 Lipids 745

_ Introduction 745

_ Classifi cation of Lipids 746

_ Simple Lipids (Fats and Oils) 747

_ Differences Between Fats and Oils 747

_ Nomenclature of Fats 748

_ Extraction of Fats 749

_ Physical and Chemical Properties of Fats and Oils 749

_ Analysis of Oils and Fats 751

_ Fatty Acids 754

_ Nomenclature of Fatty Acids 754

_ Classifi cation of Fatty Acids 755

_ Waxes 757

_ Common Waxes 757

_ Compound Lipids/Complex Lipids 758

_ Lecithins 758

_ Cephalins 759

_ Plasmalogens 759

_ Sphingomyelins 760

_ Glycolipids, Galactolipids and Cerebrosides 760

_ Derived Lipids 761

_ Sterols 762

_ Cholesterol 762

_ Lanosterol 763

_ Stigmasterol 763

_ Ergosterol 764

Index

767