Natural Products Chemistry

198 Pages·2014·2.97 MB·English

Natural Products Chemistry C
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Natural Products •
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Raymond Cooper
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Chemistry l
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George Nicola
Sources, Separations, and Structures
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Notoriously cumbersome to isolate and challenging to synthesize, the path of natural u
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products to viable drugs is an arduous journey. Yet compounds isolated from nature
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have long been known to possess fascinating structures, biological profiles, and pharma- l

ceutical potential far greater than anything made by man. Natural Products Chemistry: P
Sources, Separations, and Structures presents a practical guide to sourcing, isolating, and r
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discovering new compounds from nature many of which become pharmaceutical drugs.
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This book emphasizes the challenges and advantages of products acquired from nature,
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compared to those obtained from combinatorial chemistry.
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A basic introduction, the book describes the whole cycle from farm to final compound,
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backed by case studies drawn from industry and research applications. It broadens the
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scope of applications and draws upon examples from various sources. Natural products
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chemistry, as taught today, draws its examples mainly from marine chemistry or plant
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chemistry; however, there is also a fascinating and rich world of fermented (microbial m
and algal) products leading to complex structures. Thus, the book draws upon examples
i Natural Products
from the microbial world and from insects, too. Therefore, this is a source of bioactive s
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metabolites, not traditionally available in academic settings, more the mainstay of the r
pharmaceutical industry. y
Providing a road map of the process of collecting a compound from nature, isolat- Chemistry
ing the active ingredient, and determining the chemical structure, this book provides a
unique approach to the world of natural products.
Cover photos courtesy of Steven Foster K16349 Sources, Separations, and Structures
6000 Broken Sound Parkway, NW
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Natural Products
Chemistry
Sources, Separations, and Structures

Natural Products
Chemistry
Sources, Separations, and Structures
Raymond Cooper
George Nicola
Boca Raton London New York
CRC Press is an imprint of the
Taylor & Francis Group, an informa business
CRC Press
Taylor & Francis Group
6000 Broken Sound Parkway NW, Suite 300
Boca Raton, FL 33487-2742
© 2015 by Taylor & Francis Group, LLC
CRC Press is an imprint of Taylor & Francis Group, an Informa business
No claim to original U.S. Government works
Version Date: 20140710
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Contents
Foreword ...................................................................................................................xi
Prologue .................................................................................................................xiii
Acknowledgments ....................................................................................................xv
Authors ...................................................................................................................xvii
Introduction ................................................................................................................1
Section i Basics
Chapter 1 Natural Products Sources .....................................................................9
1.1 Primary and Secondary Metabolites .........................................9
1.2 Ethnobotany and Traditional Sources of Natural Products .....13
1.3 Sourcing of Natural Products ..................................................15
1.4 Sources of Microbes ................................................................16
1.5 Marine Sources ........................................................................16
1.6 Animal Sources .......................................................................16
1.7 Venoms and Toxins .................................................................16
Summary ............................................................................................17
Questions ............................................................................................17
Chapter 2 Extraction and Separation of Natural Products ..................................19
2.1 Water- Steam Distillation .........................................................19
2.2 Supercritical Fluid Extraction .................................................19
2.3 Solvent Partitioning .................................................................19
2.4 Refined Isolation Techniques and Chromatography ...............21
2.4.1 Separations of Nonpolar Compounds ........................21
2.4.2 Separations of Polar Compounds ...............................21
2.5 Charcoal ..................................................................................22
2.6 Reverse Phase Resins ..............................................................24
2.7 High- Performance Liquid Chromatography ...........................24
2.8 Capillary Electrophoresis ........................................................24
2.9 Polyamide Gel Chromatography .............................................24
2.10 Size- Exclusion Chromatography .............................................25
Summary ............................................................................................29
Questions ............................................................................................29
Further Reading .................................................................................29
v
vi Contents
Chapter 3 Structure Elucidation ..........................................................................31
3.1 Nuclear Magnetic Resonance ..................................................31
3.2 Ultraviolet and Infrared Spectroscopy ....................................32
3.3 Mass Spectrometry ..................................................................32
3.4 Circular Dichroism ..................................................................34
3.5 X- Ray Crystallography ............................................................34
Summary ............................................................................................38
Questions ............................................................................................39
Further Reading .................................................................................39
Chapter 4 Isomers and Building Blocks .............................................................41
4.1 Terpenes and the Isoprene Rule ...............................................41
4.2 Shikimate Pathway ..................................................................44
4.3 Mevalonate Pathway ................................................................45
4.4 Polyketides ...............................................................................45
Summary ............................................................................................47
Questions ............................................................................................47
Further Reading .................................................................................47
Section ii Selected classes of natural Products
Chapter 5 Sugar and Fat and All of That ............................................................51
5.1 Carbohydrates ..........................................................................51
5.2 Variety and Complexity of Sugars ..........................................51
5.3 Fructose and Glucose ..............................................................52
5.4 The Disaccharide Sucrose .......................................................52
5.5 Polysaccharides .......................................................................55
5.6 Galactomannan ........................................................................55
5.7 Immuno Properties of Polysaccharides: Echinacea ................56
5.8 Polysaccharides in Mushrooms: Ganoderma ..........................56
5.9 A Note on the Separation of Sugars ........................................57
5.10 Fats and Lipids .........................................................................59
5.11 Soaps ........................................................................................59
5.12 Detergents ................................................................................59
5.13 Waxes.......................................................................................59
5.14 Triglycerides ............................................................................60
5.15 Glycols .....................................................................................60
5.16 Fatty Acids ...............................................................................60
5.17 Sources of Omega Oils ............................................................60
5.18 Omega-3 Fatty Acids in Fish Oil .............................................61
5.19 Separations ..............................................................................62
5.20 Prostaglandins, Thromboxanes, and Leukotrienes .................62
Contents vii
Summary ............................................................................................63
Questions ............................................................................................64
Further Reading .................................................................................64
Chapter 6 Phenolic Compounds ..........................................................................65
6.1 Flavonoids ................................................................................65
6.2 Flavones ...................................................................................65
6.3 Isoflavones ...............................................................................66
6.4 Flavone Glycosides ..................................................................67
6.5 Anthocyanins ...........................................................................68
6.6 Tannins ....................................................................................68
6.7 Lignin and Lignans .................................................................69
6.8 Various Lignan Structural Units .............................................70
6.9 Lignans as Phytoestrogens ......................................................70
6.10 Lignans as Germination Inhibitors of Wheat ..........................73
Summary ............................................................................................75
Questions ............................................................................................75
Further Reading .................................................................................76
Chapter 7 Nitrogen- Containing Compounds ......................................................77
7.1 Proteins, Peptides, and Amino Acids ......................................77
7.1.1 Components of Proteins .............................................77
7.1.2 Protein– Peptide Building Blocks ...............................77
7.1.3 Amino Acids ..............................................................79
7.1.4 Detection of Amino Acids .........................................81
7.2 Indoles and Alkaloids ..............................................................81
7.3 Alkaloids .................................................................................83
7.4 Nucleic Acids and Base Pairings .............................................85
7.5 RNA and Protein Synthesis .....................................................86
Summary ............................................................................................87
Questions ............................................................................................87
Further Reading .................................................................................87
Section iii natural Product contributions
to Human Health
Chapter 8 Euphorics ............................................................................................91
8.1 Morphine .................................................................................91
8.2 Isolation of Morphine ..............................................................91
8.3 How Morphine Works in the Brain .........................................93
8.4 Codeine ....................................................................................93
8.5 Heroin ......................................................................................94
viii Contents
8.6 Medical Uses of Morphine ......................................................94
8.7 Cannabis ..................................................................................95
8.8 Cocaine ....................................................................................95
Summary ............................................................................................95
Questions ............................................................................................96
Further Reading .................................................................................96
Chapter 9 Anti- Infectives from Nature ...............................................................97
9.1 Antimicrobial β- Lactams ........................................................97
9.2 Structure Elucidation of Penicillin ..........................................98
9.3 Isolation of Penicillin ..............................................................99
9.4 Cephalosporin ..........................................................................99
9.5 Isolation of Cephalosporin C .................................................100
9.6 Monobactams ........................................................................100
9.7 Structural Features ................................................................101
9.8 Nocardicins ............................................................................102
9.9 Isolation .................................................................................103
9.10 Carbapenem ...........................................................................103
9.11 Structure Determination and Stability of Carbapenem .........105
9.12 Isolation of Thienamycin .......................................................105
9.13 Antibiotic Macrolides: Erythromycin ...................................106
9.14 Antiparasitic Drugs: Avermectins .........................................106
9.15 Tetracyclines ..........................................................................107
Summary ..........................................................................................108
Questions ..........................................................................................108
Further Reading ...............................................................................108
Chapter 10 Terpenes in Human Health ...............................................................111
10.1 The Statin Drugs ...................................................................111
10.2 Steroids and Cortisone ...........................................................111
10.3 Steroids from Yams ...............................................................113
10.4 Neem Oil and Other Limonoids ............................................115
10.5 Antimalarial Drugs Obtained from South America and
China .....................................................................................118
10.5.1 Quinine .....................................................................118
10.5.2 Artemisinin ..............................................................118
10.6 Anticancer Drug: Taxol from the Pacific Yew ......................118
10.7 Bryostatins .............................................................................121
Summary ..........................................................................................122
Questions ..........................................................................................122
Further Reading ...............................................................................122