Biosynthesis of Heterocycles: From Isolation to Gene Cluster

Biosynthetic studies, facilitated by the use of modern analytical techniques, have allowed researchers to purify, identify, and handle the enzymes responsible for the complex series of steps leading to natural compounds – an important source of leads for drugs and therapeutics. With recent advances, chemists frequently use biosynthetic approaches to biologically interesting compounds. Many natural products, some with potent pharmacological activity and of paramount practical importance, are based on heterocyclic frameworks. Offering a guide for the development of new drugs based on these important compounds, this book describes biosynthetic methods to synthesize heterocyclic compounds. After an introduction discussing synthetic pathways to illustrate the basics of biosynthesis, the authors explain natural products in chemistry and their formation along with important analytical methods and techniques for working with heterocycles – including isotopic labelling, enzymes and mutants, and pathway identification. Subsequent chapters describe heterocycle biosynthesis starting from natural products, with particular attention to bioactive molecules. Chemical researchers using this book come away with a number of benefits, including:  •   Coverage of methods and techniques: isotopic labelling, enzymes and mutants, and pathway identification •   A thorough resource of information specifically on heterocyclic natural products and their practical biosynthetic relevance •   Explanation of the role of natural products in chemistry and their formation •   Discussion of gene cluster identification and the use of biogenetic engineering in pharmaceutical application

Chapter 1 Introduction 1.1  Natural Products: Primary and Secondary Metabolites 1.2 Common Reactions in Secondary Metabolites References Chapter 2 Techniques for Biosynthesis 2.1 Isotopic Labeling 2.2 Gene Coding for Enzymes 2.3 Combinatorial Biosynthesis References Chapter 3 Three–Membered Heterocyclic Rings and their Fused Derivatives 3.1 Aziridines and Azirines 3.2 Oxiranes and Oxirenes References Chapter 4 Four–Membered Heterocyclic Rings and their Fused Derivatives 4.1 Azetidine and azetines 4.2 Oxetanes 4.3 Dithiethanes References Chapter 5 Five–Membered Heterocyclic Rings and their Fused Derivatives 5.1 Pyrroles (Including Tetrapyrroles) 5.2 Indoles 5.3 Furans 5.4 Thiophenes 5.5 Pyrazoles 5.6 Imidazoles 5.7 Thiazoles 5.8 Ditioles References Chapter 6 6–Membered Heterocyclic Rings and their Fused Derivatives 6.1 Pyridines and piperidines 6.2 Pyrans 6.3 Pyridazines 6.4 Pyrimidines 6.5 Pyrazines 6.6 Oxazines 6.7 Dioxanes References Chapter 7 Eight–Membered and larger Heterocyclic Rings and their Fused Derivatives 7.1 Azepines 7.2 Oxepanes and Oxepines 7.3 Diazepines, Oxazepines and Thiazepines 7.4  Diazocines 7.5  Oxocines 7.6 Erythromycin A 7.7 Tylosin 7.8 Zearalenone 7.9 Polyene macrolide antibiotics 7.10 Geldanamycin and Herbimycins 7.11 Rifamycins 7.12 Rapamycin References

Patrizia Diana is full Professor of Medicinal Chemistry at the University of Palermo. She is currently coordinator of the Medicinal and Biological Section of the Department of Science and Technology: Chemical, Biological, and Pharmaceutical (STEBICEF); and is a member of the Italian Chemical Society and International Society of Heterocyclic Chemistry. Girolamo Cirrincione is full Professor of Medicinal Chemistry at the University of Palermo. He is a member of the Drug Discovery Committee of the Pharmacology and Molecular Mechanisms (PAMM)Group of the European Organization for Research and Treatment of Cancer; the Italian Chemical Society, where he is currently serving as President of the Medicinal Chemistry Division; and the International Society of Heterocyclic Chemistry, where he served  as vice president for 2004–05