Medicinal Natural Products (eBook)

Dr Paul M Dewick, Formerly of the School of Pharmaceutical Sciences, University of Nottingham, UK (now retired). Paul Dewick is the author of Medicinal Natural Products: A Biosynthetic Approach, and Essentials of Organic Chemistry: For Students of Pharmacy, Medicinal Chemistry and Biological Chemistry (Wiley, 2006).

Medicinal Natural Products 3
CONTENTS 9
1 About this book, and how to use it 13
The subject 13
The aim 13
The approach 14
The topics 14
The figures 14
Further reading 15
What to study 15
What to learn 15
Nomenclature 15
Conventions regarding acids, bases, and ions 16
Some common abbreviations 16
Further reading 17
2 Secondary metabolism: the building blocks and construction mechanisms 19
Primary and secondary metabolism 19
The building blocks 20
The construction mechanisms 23
Alkylation reactions: nucleophilic substitution 24
Alkylation reactions: electrophilic addition 24
Wagner–Meerwein rearrangements 27
Aldol and Claisen reactions 27
Imine formation and the Mannich reaction 30
Amino acids and transamination 32
Decarboxylation reactions 34
Oxidation and reduction reactions 36
Dehydrogenases 36
Oxidases 38
Monooxygenases 38
Dioxygenases 38
Amine oxidases 39
Baeyer–Villiger monooxygenases 39
Phenolic oxidative coupling 40
Halogenation reactions 40
Glycosylation reactions 43
Elucidating biosynthetic pathways 46
Further reading 50
3 The acetate pathway: fatty acids and polyketides 51
Fatty acid synthase: saturated fatty acids 51
Unsaturated fatty acids 56
Uncommon fatty acids 65
Prostaglandins 70
Thromboxanes 76
Leukotrienes 76
Polyketide synthases: generalities 78
Polyketide synthases: macrolides 80
Polyketide synthases: linear polyketides and polyethers 102
Diels–Alder cyclizations 108
Polyketide synthases: aromatics 108
Cyclizations 111
Post-polyketide synthase modifications 115
Starter groups 128
Further reading 143
4 The shikimate pathway: aromatic amino acids and phenylpropanoids 149
Aromatic amino acids and simple benzoic acids 149
Phenylpropanoids 160
Cinnamic acids and esters 160
Lignans and lignin 163
Phenylpropenes 168
Benzoic acids from C6C3 compounds 169
Coumarins 173
Aromatic polyketides 178
Styrylpyrones, diarylheptanoids 178
Flavonoids and stilbenes 180
Flavonolignans 185
Isoflavonoids 186
Terpenoid quinones 190
Further reading 196
5 The mevalonate and methylerythritol phosphate pathways: terpenoids and steroids 199
Mevalonic acid and methylerythritol phosphate 200
Hemiterpenes (C5) 204
Monoterpenes (C10) 205
Irregular monoterpenes 216
Iridoids (C10) 218
Sesquiterpenes (C15) 222
Diterpenes (C20) 235
Sesterterpenes (C25) 246
Triterpenes (C30) 246
Triterpenoid saponins 254
Steroids 259
Stereochemistry and nomenclature 259
Cholesterol 260
Phytosterols 263
Vitamin D 268
Steroidal saponins 271
Cardioactive glycosides 277
Bile acids 287
Adrenocortical hormones/corticosteroids 289
Semi-synthesis of corticosteroids 289
Progestogens 299
Oestrogens 302
Androgens 308
Tetraterpenes (C40) 310
Higher terpenoids 318
Further reading 318
6 Alkaloids 323
Alkaloids derived from ornithine 323
Polyamines 323
Pyrrolidine and tropane alkaloids 324
Pyrrolizidine alkaloids 336
Alkaloids derived from lysine 338
Piperidine alkaloids 338
Quinolizidine alkaloids 340
Indolizidine alkaloids 342
Alkaloids derived from nicotinic acid 343
Pyridine alkaloids 343
Alkaloids derived from tyrosine 348
Phenylethylamines and simple tetrahydroisoquinoline alkaloids 348
Modified benzyltetrahydroisoquinoline alkaloids 358
Phenethylisoquinoline alkaloids 371
Terpenoid tetrahydroisoquinoline alkaloids 375
Amaryllidaceae alkaloids 377
Alkaloids derived from tryptophan 378
Simple indole alkaloids 378
Simple ?-carboline alkaloids 381
Terpenoid indole alkaloids 381
Quinoline alkaloids 392
Pyrroloindole alkaloids 397
Ergot alkaloids 399
Alkaloids derived from anthranilic acid 407
Quinazoline alkaloids 407
Quinoline and acridine alkaloids 408
Alkaloids derived from histidine 410
Imidazole alkaloids 410
Alkaloids derived by amination reactions 412
Acetate-derived alkaloids 413
Phenylalanine-derived alkaloids 413
Terpenoid alkaloids 418
Steroidal alkaloids 418
Purine alkaloids 425
Caffeine 425
Saxitoxin and tetrodotoxin 428
Further reading 429
7 Peptides, proteins, and other amino acid derivatives 433
Peptides and proteins 433
Ribosomal peptide biosynthesis 434
Peptide hormones 438
Thyroid hormones 438
Hypothalamic hormones 439
Anterior pituitary hormones 441
Posterior pituitary hormones 442
Pancreatic hormones 444
Interferons 445
Opioid peptides 446
Ribosomal peptide toxins 446
Enzymes 450
Non-ribosomal peptide biosynthesis 450
Modified peptides: penicillins, cephalosporins, and other ß-lactams 470
Penicillins 470
Cephalosporins 477
Other ?-lactams 481
Cyanogenic glycosides 488
Glucosinolates 489
Cysteine sulfoxides 492
Further reading 493
8 Carbohydrates 497
Monosaccharides 497
Oligosaccharides 502
Polysaccharides 505
Aminosugars and aminoglycosides 510
Further reading 519
Index 521

"Students should be empowered for a deductive analysis of the presented substances." (Arzneimittelforschung, December 2009)

"This new edition is an excellent text that is unrivaled in both its scope and overall coverage of natural products biosynthesis." (Journal of Medicinal Chemistry, August 2009)

"There is no question that this is the best book available on the biosynthesis and bio-organic chemistry of medicinally important natural products." (Education in Chemistry, September 2009)