Alkaloids - Geoffrey A. Cordell, Shinji Funayama

Alkaloids (eBook)

A Treasury of Poisons and Medicines

Geoffrey A. Cordell, Shinji Funayama (Autoren)

eBook Download: PDF | EPUB

2014 | 1. Auflage
294 Seiten
Elsevier Science (Verlag)
978-0-12-417314-9 (ISBN)

Alkaloids are a large group of structurally complex natural products displaying a wide range of biological activities. The purpose of Alkaloids: A Treasury of Poisons and Medicines is to classify, for the first time, the alkaloids isolated from the natural sources until now. The book classifies all of the alkaloids by their biosynthetic origins. Of interest to the organic chemistry and medicinal chemistry communities involved in drug discovery and development, this book describes many alkaloids isolated from the medicinal plants, including those used in Japanese Kampo medicine.

Classifies and lists alkaloids from natural sources
Occurrence and biosynthetic pathways of alkaloids
Indicates key uses and bioactivity of alkaloids

Alkaloids are a large group of structurally complex natural products displaying a wide range of biological activities. The purpose of Alkaloids: A Treasury of Poisons and Medicines is to classify, for the first time, the alkaloids isolated from the natural sources until now. The book classifies all of the alkaloids by their biosynthetic origins. Of interest to the organic chemistry and medicinal chemistry communities involved in drug discovery and development, this book describes many alkaloids isolated from the medicinal plants, including those used in Japanese Kampo medicine. Classifies and lists alkaloids from natural sources Occurrence and biosynthetic pathways of alkaloids Indicates key uses and bioactivity of alkaloids

Front Cover 1
Alkaloids 4
Copyright 5
CONTENTS 6
FOREWORD 10
Introduction 12
1. THE DEFINITION OF AN ALKALOID 13
LITERATURE CITED 17
2. CLASSIFICATION OF ALKALOIDS 17
LITERATURE CITED 20
3. HUMANS AND ALKALOIDS 21
LITERATURE CITED 23
4. DEVELOPMENT OF PHARMACOGNOSY AND NATURAL PRODUCT CHEMISTRY, AND ALKALOIDS 23
LITERATURE CITED 27
5. BRIEF HISTORY OF JAPANESE PHARMACEUTICAL SCIENCES AND ALKALOIDS 27
LITERATURE CITED 29
6. CNS STIMULATION AND ALKALOIDS 29
LITERATURE CITED 31
Chapter 1 - Alkaloids Derived from Phenylalanine and Tyrosine 32
1.1 PHENYLETHYLAMINES (PHENETHYLAMINES) 33
LITERATURE CITED 36
1.2 L-DOPA AND DOPAMINE 36
LITERATURE CITED 38
1.3 THYROID GLAND AND THYROXINE 38
LITERATURE CITED 39
1.4 COCLAURINE AND COCLAURINE-TYPE ALKALOIDS 40
LITERATURE CITED 42
1.5 TUBOCURARE AND D-TUBOCURARINE 43
LITERATURE CITED 45
1.6 APORPHINE-TYPE ALKALOIDS 45
LITERATURE CITED 48
1.7 ARISTOLOCHIA SPP. AND ARISTOLOCHIC ACID 48
LITERATURE CITED 51
1.8 PHELLODENDRON AMURENSE AND BERBERINE 51
LITERATURE CITED 54
1.9 CHELIDONIUM MAJUS AND CHELIDONINE 54
LITERATURE CITED 56
1.10 OPIUM AND MORPHINE 56
LITERATURE CITED 60
1.11 COLCHICUM AND COLCHICINE 60
LITERATURE CITED 62
1.12 ERYTHRINA INDICA AND ERYTHRINA ALKALOIDS 63
LITERATURE CITED 66
1.13 LYCORIS SPP. AND LYCORINE 66
LITERATURE CITED 70
1.14 CEPHAELIS IPECACUANHA AND EMETINE 70
LITERATURE CITED 72
Chapter 2 - Alkaloids Derived from Tryptophan 74
2.1 SEROTONIN 75
LITERATURE CITED 75
2.2 AUXIN AND INDOLE-3-ACETIC ACID 76
LITERATURE CITED 77
2.3 TEONANACATL AND PSILOCYBIN 77
LITERATURE CITED 78
2.4 INDIGO AND THE ANCIENT PURPLE 78
LITERATURE CITED 79
2.5 CALABAR BEANS AND PHYSOSTIGMINE 80
LITERATURE CITED 81
2.6 HARMALA AND HARMINE 81
LITERATURE CITED 82
2.7 PICRASMA SP. AND NIGAKINONE 82
LITERATURE CITED 84
2.8 CLERODENDRON AND TRICHOTOMINE 84
LITERATURE CITED 86
2.9 IBOGA AND IBOGAINE 86
LITERATURE CITED 87
2.10 RAUVOLFIA AND RESERPINE 87
LITERATURE CITED 89
2.11 YOHIMBE AND YOHIMBINE 89
LITERATURE CITED 91
2.12 CAMPTOTHECA AND CAMPTOTHECIN 91
LITERATURE CITED 93
2.13 UNCARIA AND RHYNCHOPHYLLINE 93
LITERATURE CITED 94
2.14 NUX VOMICA AND STRYCHNINE 94
LITERATURE CITED 95
2.15 CALABASH CURARE AND C-CURARINE AND C-TOXIFERINE I 95
LITERATURE CITED 96
2.16 ERGOT, ERGOT ALKALOIDS, AND LSD 96
LITERATURE CITED 99
2.17 CINCHONA AND QUININE 99
LITERATURE CITED 101
2.18 CATHARANTHUS ROSEUS AND VLB AND VCR 101
LITERATURE CITED 104
2.19 EUODIA RUTAECARPA AND EVODIAMINE AND RUTAECARPINE 104
LITERATURE CITED 106
2.20 ATHLETE’S FOOT AND PYRROLNITRIN 106
LITERATURE CITED 108
2.21 ANTHRAMYCIN AND TOMAYMYCIN 108
LITERATURE CITED 109
2.22 STREPTONIGRIN 110
LITERATURE CITED 111
2.23 STAUROSPORINE 112
LITERATURE CITED 113
Chapter 3 - Alkaloids Derived from Ornithine and Arginine 114
3.1 TOBACCO AND NICOTINE 114
LITERATURE CITED 117
3.2 BELLADONNA AND ATROPINE 117
LITERATURE CITED 122
3.3 COCA LEAVES AND COCAINE 122
LITERATURE CITED 125
3.4 SENECIO AND PYRROLIZIDINE ALKALOIDS 125
LITERATURE CITED 129
3.5 ALKALOIDS DERIVED FROM POLYAMINES 130
LITERATURE CITED 131
3.6 PUTRESCINE AND PIRIFERINE 132
LITERATURE CITED 132
3.7 SPERMIDINE AND AGROBACTIN 133
LITERATURE CITED 133
3.8 SPERMINE AND EPHEDRADINE 133
LITERATURE CITED 136
3.9 FUGU AND TETRODOTOXIN 136
LITERATURE CITED 138
Chapter 4 - Alkaloids Derived from Lysine 140
4.1 PEPPER (PIPER NIGRUM) AND PIPERINE 141
LITERATURE CITED 142
4.2 PUNICA GRANATUM AND PELLETIERINE 142
LITERATURE CITED 144
4.3 TOBACCO AND ANABASINE 145
LITERATURE CITED 146
4.4 LOBELIA INFLATA (INDIAN TOBACCO) AND LOBELINE 146
LITERATURE CITED 147
4.5 SOPHORA FLAVESCENS AND MATRINE 147
LITERATURE CITED 149
4.6 COMMON BROOM (CYTISUS SCOPARIUS) AND SPARTEINE 150
LITERATURE CITED 151
Chapter 5 - Alkaloids Derived from Proline 152
Anchor 40 152
LITERATURE CITED 153
5.1 SERRATIA AND PRODIGIOSIN 153
LITERATURE CITED 154
5.2 STACHYDRINE 155
LITERATURE CITED 155
5.3 PYRROLE-2-CARBOXYLIC ACID 155
LITERATURE CITED 156
Chapter 6 - Alkaloids Derived from Glutamic Acid 158
6.1 G-AMINOBUTYRIC ACID 158
LITERATURE CITED 159
6.2 DIGENEA SIMPLEX AND KAINIC ACID 160
LITERATURE CITED 161
6.3 CLITOCYBE ACROMELALGA AND ACROMELIC ACID 162
LITERATURE CITED 164
6.4 AMANITA PANTHERINA AND IBOTENIC ACID 164
LITERATURE CITED 165
Chapter 7 - Alkaloids Derived from Histidine 166
7.1 HISTAMINE 166
LITERATURE CITED 168
7.2 JABORANDI AND PILOCARPINE 168
LITERATURE CITED 168
Chapter 8 - Alkaloids Derived from 2,3-Diamino propionic Acid 170
8.1 QUISQUALIS INDICA FRUITS AND QUISQUALIC ACID 170
LITERATURE CITED 171
Chapter 9 - Compounds Derived from Anthranilic Acid 174
LITERATURE CITED 175
9.1 ORIXA JAPONICA AND QUINOLINE ALKALOIDS 175
LITERATURE CITED 178
9.2 QUINOLINE ALKALOIDS OF MICROBIAL ORIGIN 179
LITERATURE CITED 180
9.3 ACRONYCINE AND ACRIDONE ALKALOIDS 180
LITERATURE CITED 182
9.4 QUINOLINE ALKALOIDS ISOLATED FROM HIGHER PLANTS OTHER THAN THE RUTACEAE FAMILY 183
LITERATURE CITED 184
9.5 FEBRIFUGINE AND RELATED ALKALOIDS 184
LITERATURE CITED 186
9.6 HARMALA ALKALOIDS AND VASICINE (PEGANINE) 187
LITERATURE CITED 188
9.7 PHENAZINE ALKALOIDS DERIVED FROM MICROORGANISMS 189
LITERATURE CITED 191
Chapter 10 - Alkaloids Derived from Nicotinic Acid 192
Anchor 79 192
LITERATURE CITED 194
10.1 NICOTINE AND ANABASINE 195
LITERATURE CITED 197
10.2 NIACIN AND VITAMIN B6 197
LITERATURE CITED 199
10.3 ARECA NUT AND ARECOLINE 200
LITERATURE CITED 201
10.4 CASTOR AND RICININE 201
LITERATURE CITED 203
Chapter 11 - Alkaloids Derived from Nucleic Acids and Related Compounds 204
11.1 PURINE BASES AND CAFFEINE 205
LITERATURE CITED 212
11.2 PYRIMIDINE BASES, 5-FLUOROURACIL, AND VITAMIN B1 213
LITERATURE CITED 217
11.3 PTERIDINE SKELETON AND FOLIC ACID 217
LITERATURE CITED 219
Chapter 12 - Alkaloids Possessing the Porphine Skeleton 220
LITERATURE CITED 221
12.1 HEME AND CHLOROPHYLL 221
LITERATURE CITED 226
12.2 VITAMIN B12 227
LITERATURE CITED 228
Chapter 13 - Alkaloids Derived from an m-C7N Unit 230
13.1 MITOMYCIN C 231
LITERATURE CITED 232
13.2 NAPHTHALENOID ANSAMYCINS AND RIFAMPICIN 233
LITERATURE CITED 236
13.3 BENZENOID ANSAMYCINS AND MAYTANSINE 236
LITERATURE CITED 239
13.4 THE BIOSYNTHESIS–STEREOCHEMISTRY MODEL (CELMER’S MODEL) OF THE ANSAMYCINS 239
LITERATURE CITED 243
Chapter 14 - Alkaloids Derived from Terpenoids 244
Anchor 173 244
LITERATURE CITED 247
14.1 ACTINIDIA POLYGAMA AND ACTINIDINE 247
LITERATURE CITED 249
14.2 GENTIANA SCABRA AND GENTIANINE 249
LITERATURE CITED 251
14.3 RHIZOME OF NUPHAR JAPONICUM AND SESQUITERPENE ALKALOIDS 251
LITERATURE CITED 252
14.4 ACONITUM AND ACONITINE ALKALOIDS 252
LITERATURE CITED 255
14.5 TAXUS CUSPIDATA AND TAXOL 255
LITERATURE CITED 257
14.6 PACHYSANDRA TERMINALIS AND BUXACEAE ALKALOIDS 257
LITERATURE CITED 259
14.7 HOLARRHENA ANTIDYSENTERICA AND CONESSINE 259
LITERATURE CITED 259
14.8 POTATO AND SOLANINE 259
LITERATURE CITED 261
14.9 FRITILLARIA AND VERATRUM ALKALOIDS 261
LITERATURE CITED 263
14.10 ARROW TOXINS, TOXIC BIRDS, AND BATRACHOTOXIN 264
LITERATURE CITED 266
Chapter 15 - Alkaloids Derived from Polyketides 268
15.1 HEMLOCK AND CONIINE 268
LITERATURE CITED 270
15.2 NIGRIFACTIN AND PIERICIDINS 271
LITERATURE CITED 272
Chapter 16 - Alkaloids Derived from a C6–C1 Unit 274
16.1 EPHEDRA ALKALOIDS 275
LITERATURE CITED 278
16.2 KHAT AND EPHEDRA ALKALOIDS 278
LITERATURE CITED 280
16.3 NAPHTHALENE-ISOQUINOLINE ALKALOIDS 281
LITERATURE CITED 282
16.4 RED PEPPER AND CAPSAICIN 282
LITERATURE CITED 284
INDEX 286

Introduction

Before describing the various groups of alkaloids individually, the place of alkaloids among the naturally occurring organic compounds, and in society will be discussed briefly in this chapter.

An understanding of what an alkaloid is will be mentioned in the first section, and in the second section, the aspects of classifying alkaloids on the basis of their biosynthetic origin will be presented. This method will be compared with a classification based on their carbon or heterocyclic skeleton, such as indole, isoquinoline alkaloids, or a classification of the alkaloids based on a chemotaxonomic approach, such as Rutaceae and Apocynaceae alkaloids. A short history of the study of alkaloids and the crude drugs as the origin of various alkaloids, and their relevance in the history of natural products chemistry will be described. Through these discussions, it will be established that the natural products classified as alkaloids relate to our life deeply, and on an everyday basis, as medicines, as dyestuffs, as flavors, as stimulants, and as toxic substances.

It is known that alkaloids show a broad range of biological activities. Among the biologically active compounds, there are especially many alkaloids which affect the central nervous system (CNS) and the autonomic nervous system. Some of the CNS stimulants will be described in the final sixth section.

Readers of this book will discover that alkaloids are a very important group of organic compounds which show a variety of highly significant, clinically and biologically useful properties. Among these activities of alkaloids are hypotensive, cardiotonic, hormone, pheromone, growth acceleration, antimalarial, antitumor, antiparasitic, sedative, analgesic, anti-Alzheimer’s, and antimicrobial activities.

There are probably over 25,000 alkaloids derived from higher plants as presented in the Dictionary of Alkaloids. This modest volume offers a brief overview of the main alkaloid groups, their structures, their activities, and their basic biosynthetic pathways from a historical perspective.

The Definition of An Alkaloid

The word “alkaloid” was proposed in 1818 by K. F. W. Meissner (1792–1853), a pharmacist in Halle, Germany. The word alkaloid was coined from the word alkali (implying basicity), from “ ” (referring to soda) in Arabic. The “-oid” suffix, meaning “like”, derives from the Greek.

The definition of an alkaloid has changed significantly over the years, as more “alkaloids” have been structurally elucidated and the sources of alkaloids have broadened.

1. At the beginning, alkaloids were discovered only from higher plants, and those compounds showed basic properties and strong biological activities. Consequently, at that time, an alkaloid was defined as “the plant component which shows basic properties and strong biological effect.” The basicity of alkaloids is derived from the presence of a nitrogen atom in the molecule in the form of an amine.

Such a definition is no longer possible for the alkaloids. First of all, alkaloids are obtained from an extremely broad range of natural sources, not just the plant kingdom. For example, retronecine, danaidone, and hydroxydanaidal (derivatives of pyrrolizidine alkaloids) were isolated from the hair pencil of the male butterfly of the Danaid genus. Batrachotoxin, a poison arrow toxin component, was isolated from the skin of a frog. In addition, there are many examples of alkaloids of microbial, marine, and human origin, including a vast array of nitrogen-containing antibiotics.

2. Alkaloids are not limited to those natural products which are basic in character. For example, colchicine isolated from Colchicum autumnale (Liliaceae) and used for the treatment of gout, etc. is not basic because the nitrogen atom in the molecule is present in a neutral amide group. However, the biosynthetic precursor of colchicine is autumnaline, a typical, basic phenethylisoquinoline alkaloid. Therefore any compound derived from such an intermediate should be classified as an alkaloid.

Another example pertains to the close structural isomers, pteleprenine and isopteleprenine, which were isolated from Orixa japonica (Rutaceae). In pteleprenine, the nitrogen is in the form of an amide, and therefore it lacks basicity. On the other hand, in isopteleprenine the nitrogen atom, being in a quinoline ring, is weakly basic. Given their common biosynthetic origin both compounds are classified as alkaloids.

In the case of the phenanthrine derivative aristolochic acid-I, the skeleton is derived from an aporphine alkaloid precursor which has undergone oxidation, to the point where the nitrogen atom exists as a nitro group. Biosynthetically, this compound is also classed as an alkaloid.

3. It is not appropriate to include the existence of biological activity in the definition for an alkaloid. Several years ago [1] it was shown that about 75% of known “alkaloids” had never been tested in a single bioassay. In addition, when an alkaloid with biological activity is isolated, compounds with a closely related chemical structure with no, or greatly diminished, biological activities will also be isolated. In such a case, all of these compounds are regarded as alkaloids, irrespective of whether they have a demonstrated biological activity.

4. Alkaloids are always compounds isolated from nature. However, there are many examples of alkaloid derivatives with a high profile which may be confused and sometimes classified as alkaloids. For example, Lyserg Säure Diäthylamid (LSD) (LSD-25) is prepared by the amidation of lysergic acid, itself derived from the ergot alkaloids. Methamphetamine is prepared by the reduction of (−)-ephedrine, and heroin is prepared by the acetylation of morphine, and there are many derivatives of alkaloids which are pharmaceutical products. These semisynthetic compounds can be classed as alkaloid derivatives.

5. There are a significant number of unusual amino acids, simple peptides, pyrrole derivatives, and comparatively simple nitrogen-containing organic compounds, including purines and pyrimidines, which may be excluded from classification as alkaloids.

For example, L-α-kainic acid, obtained from the red algae Digenea simplex (Rhodomelaceae), might not be regarded as an alkaloid. However, this unusual amino acid is biosynthesized from L-glutamic acid and an hemiterpenoid unit, and therefore it is classified as an alkaloid rather than unusual amino acid.

The pyrazolopyrimidines, such as caffeine of tea and coffee origin, are alkaloids, as is the phytohormone zeatin from maize.

Also, comparatively simple N-containing compounds (amines), such as serotonin and histamine, are alkaloids, as are mescaline, isolated from the peyote cactus, Lophophora williamsii, and (+)-coniine obtained from Conium maculatum.

Based on the above discussion, the precise definition of an alkaloid is rather unclear. That is appropriate for such a broadly available, structurally diverse group of metabolites. It may be said that alkaloids are naturally occurring, nitrogen-containing compounds. The group excludes the amino acids of primary metabolism, complex peptides and proteins constructed from those amino acids, and nucleic acids. Thus we see alkaloids, not in terms of a comprehensive definition, but rather as a way to classify a large number of natural metabolites containing nitrogen possessing great structural diversity and derived from any natural source. As has been suggested previously, with experience, “you know one when you see one” [2]. Our task then is to classify them so that the breadth and depth of their molecular frameworks can be assimilated into the larger organization of natural product structures.

Literature Cited

[1] Cordell G.A, Quinn-Beattie M.L, Farnsworth N.R. Phytother. Res. 2001;15:183–205.

[2] Cordell G.A. Introduction to Alkaloids. A Biogenetic Approach. New York, NY: Wiley Interscience; 1981 1055 pages.

Classification of Alkaloids

Several approaches to the classification of alkaloids are available, including, chemical, taxonomic, biological, and biosynthetic. At various times, each of these approaches has been used in terms of the presentation and discussion of alkaloid development. We will discuss these approaches in turn.

Alkaloids were often classified on the basis of their chemical structure. According to this system, alkaloids are organized based on a common, typically heterocyclic, nucleus, such as isoquinoline, indole, quinolone, quinazoline, pyrrolizidine, and tropane alkaloids, etc. Another method to classify the alkaloids, is to use their natural origin. So we could organize them based on a plant family, such as Amaryllidaceae, Solanaceae, and Rutaceae alkaloids, or based on a genus, such the Catharanthus alkaloids. Classification may use the name of a prototypical alkaloid of the group such as aconitine-type or morphine-type alkaloids. Frequently, this approach also follows a common biosynthetic or biogenetic...

Erscheint lt. Verlag	1.11.2014
Sprache	englisch
Themenwelt	Medizin / Pharmazie ► Gesundheitsfachberufe
	Medizin / Pharmazie ► Medizinische Fachgebiete ► Pharmakologie / Pharmakotherapie
	Naturwissenschaften ► Biologie ► Biochemie
	Naturwissenschaften ► Chemie ► Organische Chemie
	Technik
ISBN-10	0-12-417314-4 / 0124173144
ISBN-13	978-0-12-417314-9 / 9780124173149

Haben Sie eine Frage zum Produkt?

PDF (Adobe DRM)
Größe: 13,2 MB

Kopierschutz: Adobe-DRM
Adobe-DRM ist ein Kopierschutz, der das eBook vor Mißbrauch schützen soll. Dabei wird das eBook bereits beim Download auf Ihre persönliche Adobe-ID autorisiert. Lesen können Sie das eBook dann nur auf den Geräten, welche ebenfalls auf Ihre Adobe-ID registriert sind.
Details zum Adobe-DRM

Dateiformat: PDF (Portable Document Format)
Mit einem festen Seitenlayout eignet sich die PDF besonders für Fachbücher mit Spalten, Tabellen und Abbildungen. Eine PDF kann auf fast allen Geräten angezeigt werden, ist aber für kleine Displays (Smartphone, eReader) nur eingeschränkt geeignet.

Systemvoraussetzungen:
PC/Mac: Mit einem PC oder Mac können Sie dieses eBook lesen. Sie benötigen eine Adobe-ID und die Software Adobe Digital Editions (kostenlos). Von der Benutzung der OverDrive Media Console raten wir Ihnen ab. Erfahrungsgemäß treten hier gehäuft Probleme mit dem Adobe DRM auf.
eReader: Dieses eBook kann mit (fast) allen eBook-Readern gelesen werden. Mit dem amazon-Kindle ist es aber nicht kompatibel.
Smartphone/Tablet: Egal ob Apple oder Android, dieses eBook können Sie lesen. Sie benötigen eine Adobe-ID sowie eine kostenlose App.
Geräteliste und zusätzliche Hinweise

Buying eBooks from abroad
For tax law reasons we can sell eBooks just within Germany and Switzerland. Regrettably we cannot fulfill eBook-orders from other countries.

EPUB (Adobe DRM)

Dateiformat: EPUB (Electronic Publication)
EPUB ist ein offener Standard für eBooks und eignet sich besonders zur Darstellung von Belletristik und Sachbüchern. Der Fließtext wird dynamisch an die Display- und Schriftgröße angepasst. Auch für mobile Lesegeräte ist EPUB daher gut geeignet.

Buying eBooks from abroad
For tax law reasons we can sell eBooks just within Germany and Switzerland. Regrettably we cannot fulfill eBook-orders from other countries.

Print-Ausgabe

Buch | Hardcover

179,95 €