Medicinal Natural Products

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).

• 1 About this book, and how to use it 1The subject 1The aim 1The approach 2The topics 2The figures 2Further reading 3What to study 3What to learn 3Nomenclature 3Conventions regarding acids, bases, and ions 4Some common abbreviations 4Further reading 52 Secondary metabolism: the building blocks and construction mechanisms 7Primary and secondary metabolism 7The building blocks 8The construction mechanisms 11Alkylation reactions: nucleophilic substitution 12Alkylation reactions: electrophilic addition 12Wagner–Meerwein rearrangements 15Aldol and Claisen reactions 15Imine formation and the Mannich reaction 18Amino acids and transamination 20Decarboxylation reactions 22Oxidation and reduction reactions 24Dehydrogenases 24Oxidases 26Monooxygenases 26Dioxygenases 26Amine oxidases 27Baeyer–Villiger monooxygenases 27Phenolic oxidative coupling 28Halogenation reactions 28Glycosylation reactions 31Elucidating biosynthetic pathways 34Further reading 383 The acetate pathway: fatty acids and polyketides 39Fatty acid synthase: saturated fatty acids 39Unsaturated fatty acids 44Uncommon fatty acids 53Prostaglandins 58Thromboxanes 64Leukotrienes 64Polyketide synthases: generalities 66Polyketide synthases: macrolides 68Polyketide synthases: linear polyketides and polyethers 90Diels–Alder cyclizations 96Polyketide synthases: aromatics 96Cyclizations 99Post-polyketide synthase modifications 103Starter groups 116Further reading 1314 The shikimate pathway: aromatic amino acids and phenylpropanoids 137Aromatic amino acids and simple benzoic acids 137Phenylpropanoids 148Cinnamic acids and esters 148Lignans and lignin 152Phenylpropenes 156Benzoic acids from C 6 C 3 compounds 157Coumarins 161Aromatic polyketides 166Styrylpyrones, diarylheptanoids 166Flavonoids and stilbenes 167Flavonolignans 173Isoflavonoids 174Terpenoid quinones 178Further reading 1845 The mevalonate and methylerythritol phosphate pathways: terpenoids and steroids 187Mevalonic acid and methylerythritol phosphate 188Hemiterpenes (C 5) 192Monoterpenes (C 10) 193Irregular monoterpenes 204Iridoids (C 10) 206Sesquiterpenes (C 15) 210Diterpenes (C 20) 223Sesterterpenes (C 25) 234Triterpenes (C 30) 234Triterpenoid saponins 242Steroids 247Stereochemistry and nomenclature 247Cholesterol 248Phytosterols 251Vitamin d 256Steroidal saponins 259Cardioactive glycosides 265Bile acids 275Adrenocortical hormones/corticosteroids 277Semi-synthesis of corticosteroids 277Progestogens 287Oestrogens 290Androgens 296Tetraterpenes (C 40) 298Higher terpenoids 306Further reading 3066 Alkaloids 311Alkaloids derived from ornithine 311Polyamines 311Pyrrolidine and tropane alkaloids 312Pyrrolizidine alkaloids 324Alkaloids derived from lysine 326Piperidine alkaloids 326Quinolizidine alkaloids 328Indolizidine alkaloids 330Alkaloids derived from nicotinic acid 331Pyridine alkaloids 331Alkaloids derived from tyrosine 336Phenylethylamines and simple tetrahydroisoquinoline alkaloids 336Modified benzyltetrahydroisoquinoline alkaloids 346Phenethylisoquinoline alkaloids 359Terpenoid tetrahydroisoquinoline alkaloids 363Amaryllidaceae alkaloids 365Alkaloids derived from tryptophan 366Simple indole alkaloids 366Simple β-carboline alkaloids 369Terpenoid indole alkaloids 369Quinoline alkaloids 380Pyrroloindole alkaloids 385Ergot alkaloids 387Alkaloids derived from anthranilic acid 395Quinazoline alkaloids 395Quinoline and acridine alkaloids 396Alkaloids derived from histidine 398Imidazole alkaloids 398Alkaloids derived by amination reactions 400Acetate-derived alkaloids 401Phenylalanine-derived alkaloids 401Terpenoid alkaloids 406Steroidal alkaloids 406Purine alkaloids 413Caffeine 413Saxitoxin and tetrodotoxin 416Further reading 4177 Peptides, proteins, and other amino acid derivatives 421Peptides and proteins 421Ribosomal peptide biosynthesis 422Peptide hormones 426Thyroid hormones 426Hypothalamic hormones 427Anterior pituitary hormones 429Posterior pituitary hormones 430Pancreatic hormones 432Interferons 433Opioid peptides 434Ribosomal peptide toxins 434Enzymes 438Non-ribosomal peptide biosynthesis 438Modified peptides: penicillins, cephalosporins, and other β-lactams 458Penicillins 458Cephalosporins 465Other β-lactams 469Cyanogenic glycosides 476Glucosinolates 477Cysteine sulfoxides 480Further reading 4818 Carbohydrates 485Monosaccharides 485Oligosaccharides 490Polysaccharides 493Aminosugars and aminoglycosides 498Further reading 507Index 509

"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)