PREFACE ...................................................... xiii
ACKNOWLEDGMENTS ................................................ xv
1 Introduction ............................................... 1
1.1 Natural Products: Primary and Secondary Metabolites ........ 4
1.2 Common Reactions in Secondary Metabolites .................. 6
1.2.1 Alkylations ......................................... 6
1.2.2 Wagner-Meerwein Rearrangements ..................... 16
1.2.3 Aldol and Claisen Reactions ........................ 17
1.2.4 Schiff Base Formation and Mannich Reactions ........ 23
1.2.5 Transaminations .................................... 25
1.2.6 Decarboxylations ................................... 26
1.2.7 Oxidation and Reduction Reactions .................. 31
1.2.8 Dehalogenation/Halogenation Reactions .............. 39
1.2.9 Glycosylation Reactions ............................ 46
References ................................................ 48
2 Techniques for Biosynthesis ............................... 51
2.1 Isotopic Labeling ......................................... 52
2.1.1 Stable Isotopes .................................... 52
2.1.2 Radioactive Isotopes ............................... 61
2.2 Gene Coding for Enzymes ................................... 62
2.3 Combinatorial Biosynthesis ................................ 63
References ................................................ 70
3 Three-Membered Heterocyclic Rings and Their Fused
Derivatives ............................................... 73
3.1 Aziridines and Azirines ................................... 73
3.1.1 Azicemicins ........................................ 73
3.1.2 Miraziridine ....................................... 74
3.1.3 Maduropeptin ....................................... 75
3.1.4 Azinomycins ........................................ 79
3.1.5 Ficellomycin ....................................... 87
3.1.6 Mitomycins ......................................... 89
3.1.7 Azirinomycin and Related Azirines ................. 101
3.2 Oxiranes and Oxirenes .................................... 104
3.2.1 Fosfomycin ........................................ 104
3.2.2 AK, HC, and AF toxins ............................. 111
3.2.3 Cerulenin ......................................... 117
3.2.4 Polyhydroxyalkanoates ............................. 118
3.2.5 Epoxyrollins ...................................... 118
3.2.6 Asperlactone, Aspyrone, Asperline ................. 121
3.2.7 Tajixanthone ...................................... 129
3.2.8 Cyclomarin ........................................ 133
3.2.9 Cyclopenin ........................................ 139
3.2.10 Ovalicin and Fumagillin ........................... 141
3.2.11 Methylenomycin A .................................. 143
3.2.12 Antibiotic LL-C10037 .............................. 147
3.2.13 Manumycins ........................................ 151
3.2.14 Scopolamine ....................................... 164
3.2.15 Iridoid Glucosides ................................ 169
3.2.16 Cordiaquinone ..................................... 172
3.2.17 Cyclizidine and Indolizomycin ..................... 172
3.2.18 Enediyne Antibiotics .............................. 175
3.2.19 Macrolides ........................................ 195
3.2.20 Epothilones ....................................... 225
3.2.21 Pimaricin ......................................... 233
3.2.22 Hypothemycin ...................................... 240
3.2.23 Radicicol and Monocillin I ........................ 243
3.2.24 Trichothecenes .................................... 248
3.2.25 Sporolides A and B ................................ 255
References ............................................... 258
4 Four-Membered Heterocyclic Rings and Their Fused
Derivatives .............................................. 277
4.1 Azetidine and Azetines ................................... 277
4.1.1 Azetidine-2-carboxylic acid ....................... 277
4.1.2 Polyoxins ......................................... 280
4.1.3 Mugineic Acids .................................... 288
4.1.4 Tabtoxin and Tabtoxinine-ß-lactam ................. 293
4.1.5 Nocardicins ....................................... 296
4.1.6 Thienamycin ....................................... 303
4.1.7 Clavulanic Acid and Clavams ....................... 311
4.1.8 Penicillins and Cephalosporins .................... 319
4.2 Oxetanes ................................................. 341
4.2.1 Oxetanocins ....................................... 341
4.2.2 Salinosporamides .................................. 342
4.2.3 Taxol ............................................. 352
4.3 Dithiethanes ............................................. 363
4.3.1 Tropodithietic acid and Thiotropocin .............. 363
References ............................................... 367
5 Five-Membered Heterocyclic Rings and Their Fused
Derivatives .............................................. 379
5.1 Pyrroles (Including Tetrapyrroles) ....................... 379
5.1.1 2-Acetyl-1-pyrroline .............................. 379
5.1.2 Pyrrolnitrin ...................................... 380
5.1.3 Broussonetines .................................... 385
5.1.4 Prodigiosin and Undecylprodigiosin ................ 386
5.1.5 Anatoxin-a and Homoanatoxin-a ..................... 402
5.1.6 Nostopeptolides A ................................. 407
5.1.7 Pyrrolizidine Alkaloids ........................... 410
5.1.8 Toyocamycin and Sangivamycin ...................... 416
5.1.9 Tetrapyrroles ..................................... 420
5.2 Indoles .................................................. 428
5.2.1 Indole-3-acetic acid and Glucobrassicin ........... 428
5.2.2 Camalexin ......................................... 439
5.2.3 Cyclomarazines .................................... 444
5.2.4 Rebeccamycin and Staurosporine .................... 445
5.2.5 Paxilline ......................................... 455
5.3 Furans ................................................... 460
5.3.1 Furanomycin ....................................... 460
5.3.2 Xenofuranones A and B ............................. 462
5.3.3 Acyl α-L-Rhamnopyranosides and Rhamnosyllactones .. 463
5.3.4 Tuscolid and Tuscoron A and B ..................... 466
5.3.5 Tetronomycin and Tetronasin ....................... 469
5.3.6 Nonactin and Macrotetrolides ...................... 474
5.3.7 Furanonaphthoquinone I ............................ 481
5.4 Thiophenes ............................................... 488
5.5 Pyrazoles ................................................ 489
5.6 Imidazoles ............................................... 490
5.6.1 Histidine ......................................... 490
5.6.2 Amaranzole A ...................................... 493
5.6.3 Oroidin ........................................... 493
5.6.1 Nikkomycins ....................................... 493
5.6.5 Anosmine .......................................... 496
5.7 Thiazoles ................................................ 497
5.7.1 Thiamin (Vitamin В1) .............................. 497
5.7.2 Polypeptide Antibiotics ........................... 502
5.7.3 Barbamide ......................................... 508
5.7.4 BE-10988 .......................................... 508
5.7.5 Pheomelanins ...................................... 510
5.8 Dithioles ................................................ 511
References ............................................... 516
6 Six-Membered Rings, and Their Fused Derivatives
6.1 Pyridines and Piperidines ................................ 533
6.1.1 Pyridoxal 5'-phosphate ............................ 533
6.1.2 Nicotinamide Adenine Dinucleotide ................. 536
6.1.3 Nicotine and Related Compounds .................... 540
6.1.4 Tropane Alkaloids ................................. 542
6.1.5 Stenusine ......................................... 543
6.1.6 Antidesmone ....................................... 546
6.1.7 Quinolobactin ..................................... 546
6.1.8 Pyridomycin ....................................... 546
6.1.9 Lycopodine ........................................ 550
6.1.10 Acridone Alkaloids ................................ 551
6.1.11 Benzylisoquinolines ............................... 551
6.1.12 Saframycins ....................................... 559
6.2 Pyrans ................................................... 561
6.2.1 Lovastatin and Compactin .......................... 561
6.2.2 Bafilomycins and Concanamycin ..................... 567
6.2.3 Citrinin .......................................... 571
6.2.4 Aminocoumarin Antibiotics ......................... 571
6.2.5 Flavonoids ........................................ 577
6.2.6 Actinorhodin and Granaticin ....................... 581
6.2.7 Trichothecenes .................................... 582
6.2.8 Gilvocarcins ...................................... 582
6.3 Pyridazines .............................................. 586
6.3.1 Kutznerides ....................................... 586
6.3.2 Pyridazomycin ..................................... 591
6.3.3 Azamerone ......................................... 591
6.4 Pyrimidines .............................................. 592
6.4.1 Purine and Pyrimidine Nucleotides ................. 592
6.4.2 Methylxanthines and Methyluric Acids .............. 602
6.4.3 Cytokinins ........................................ 606
6.4.4 Uridyl Peptide Antibiotics ........................ 607
6.4.5 Riboflavin, FMN, and FAD .......................... 611
6.5 Pyrazines ................................................ 613
6.5.1 Alkyl and Methoxy Pyrazines ....................... 613
6.5.2 Pteridines ........................................ 616
6.5.3 Epipolythiodioxopiperazines ....................... 617
6.5.4 Roquefortine С and Related Compounds .............. 621
6.6 Oxazines ................................................. 622
6.6.1 Minimycin ......................................... 622
6.6.2 Benzoxazinoids .................................... 625
6.7 Dioxanes ............................................ 626
6.7.1 Plakortolides ..................................... 626
6.7.2 Alnumycin ......................................... 627
References ............................................... 632
7 Seven-Eight-Membered and Larger Heterocyclic Rings
and Their Fused Derivatives .............................. 649
7.1 Azepines ................................................. 649
7.2 Oxepanes and Oxepines .................................... 657
7.3 Diazepines, Oxazepines, and Thiazepines .................. 661
7.4 Diazocines ............................................... 674
7.5 Oxocines ................................................. 674
7.6 Erythromycin A ........................................... 675
7.7 Tylosin .................................................. 683
7.8 Zearalenone .............................................. 690
7.9 Polyene Macrolide Antibiotics ............................ 693
7.9.1 Nystatin and Amphotericin ......................... 694
7.9.2 Candicidin D ...................................... 705
7.10 Geldanamycin and Herbimycins ............................. 716
7.11 Rifamycins ............................................... 724
7.12 Rapamycin ................................................ 738
References ............................................... 745
INDEX ......................................................... 757
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