The Organic Chemistry of Isotopic Labelling

by Hanson, James R.

• ISBN13: 9781849731881
• ISBN10: 1849731888
• Format: Hardcover
• Copyright: 2011-01-24
• Publisher: Royal Society of Chemistry

Summary

The chemical synthesis of isotopically labelled compounds is a pre-requisite for many chemical, biochemical and medicinal investigations. The constraints imposed by the requirements for regiospecific labelling and, in some instances, the time-scale of the synthesis often lead to quite different synthetic strategies to those that are used for the unlabelled material. Whilst there are many specialist papers, reviews and long books devoted to particular isotopes, there is no currently available short introductory book devoted to the organic chemistry of isotopic labelling. The aim of this book is to introduce research workers to a variety of methods that have been used to achieve these synthetic labelling objectives before exploring a particular method in detail. It covers a number of different isotopes and the methods that have been used to introduce them into organic compounds. Labelling methods also provide useful undergraduate teaching examples of modern synthetic reactions and their stereochemical consequences using relatively simple substrates. The book will therefore have a wider appeal than just those involved in using isotopes in research such as environmental and pharmaceutical chemists as well as organic chemists.

Table of Contents

An Introduction to the Organic Chemistry of Isotopic Labelling	p. xiii
The Discovery and Detection of Isotopes	p. 1
Introduction	p. 1
The Discovery of Isotopes	p. 2
Early Applications of Isotopically Labelled Compounds	p. 5
The Selection of an Isotopic Label	p. 9
The Detection oflsotopes	p. 13
Nomenclature	p. 18
Labelling Compounds with Carbon-13 and Carbon-14	p. 20
Introduction	p. 20
Carbon Labelling Using the Cyanide Jon	p. 21
Organometallic Reagents in Carbon Labelling	p. 24
The Wittig Reaction in Carbon Labelling	p. 27
Carbonyl Condensation Reactions in Carbon Labelling	p. 28
The Synthesis of Carbon-labelled Mevalonic Acid	p. 31
Aromatic Compounds Labelled in the Ring	p. 33
Ring-labelled Heterocyclic Compounds	p. 35
Biosynthetic Methods of Carbon Labelling	p. 38
Labelling with Deuterium and Tritium	p. 40
Introduction	p. 40
The Kinetic Isotope Effect	p. 41
The Isolation of Deuterium and Tritium	p. 42
Exchange Reactions in Deuterium and Tritium Labelling	p. 43
Heteroatom X-H Exchange Reactions	p. 44
General C-H Exchange Reactions	p. 44
Site-specific C-H Exchange Reactions	p. 45
Exchange Reactions of Carbonyl Compounds	p. 49
Exchange Reactions in the Preparation of Some Deuteriated Solvents	p. 51
Decarboxylation Reactions in Deuterium and TritiumLabelling	p. 51
Reduction Reactions	p. 52
Reducing Agents	p. 52
The Reduction of Carbonyl Groups	p. 54
The Hydrogenolysis of Aliphatic Substituents	p. 54
The Catalytic Reduction of Alkenes and Alkynes	p. 54
The Hydrogenolysis of Aryl Halides	p. 56
The Reduction of Iminium Salts	p. 58
The Hydrogenolysis of Organometallic Compounds	p. 58
Hydroboration	p. 59
Deuterium- and Tritium-labelled Alkyl Halides	p. 60
Stereochemical Aspects of Labelling with Hydrogen Isotopes	p. 62
Introduction	p. 62
The Application of the Cahn-Ingold-Prelog Sequence Rules to Labelled Compounds	p. 63
The Stereochemistry of Reactions Used in Labelling	p. 64
Labelled Steroids	p. 69
Labelled Gibberellin Plant Hormones	p. 73
The Chiral Methyl Group	p. 75
Stereospecifically Labelled Mevalonic Acid	p. 78
Stereospecifically Labelled Isopentenyl Diphosphate	p. 81
Labelling of 1-Deoxy-D-xylulose	p. 83
The Stereochemistry of Hydrogen Transfer from the Nicotinamide Coenzymes	p. 84
The Synthesis of Labelled Amino Acids	p. 86
Introduction	p. 86
The Synthesis of Racemic Labelled Amino Acids	p. 87
Labelled Enantiopure Amino Acids	p. 89
The Labelling of Some Compounds of Pharmaceutical Interest	p. 96
Introduction	p. 96
Lidocaine	p. 97
Non-steroidal Anti-inflammatory Agents	p. 98
Amphetamines	p. 101
Sulfonamides	p. 102
Morphine and Its Relatives	p. 103
Galanthamine	p. 106
Tropane Alkaloids	p. 107
Tryptamine Derivatives	p. 108
Labelling Compounds with the Stable Isotopes of Nitrogen and Oxygen	p. 110
Nitrogen-15	p. 110
Oxygen-17 and Oxygen-18	p. 116
Labelling with Isotopes of Phosphorus, Sulfur and the Halogens122
Phosphorus-32	p. 122
Sulfur-34 and Sulfur-35	p. 124
Chlorine-36	p. 126
Iodine Isotopes	p. 126
Labelling Organic Compounds for Diagnostic Imaging	p. 129
Introduction	p. 129
Positron Emission Tomography	p. 129
Carbon-11 in PET	p. 131
Fluorine-18 in PET	p. 135
Nitrogen-13 in PET	p. 141
Oxygen-15 in PET	p. 141
Isotopes of Bromine	p. 141
Positron-emitting Metallic Isotopes in PET	p. 142
Single Photon Emission Computed Tomography	p. 143
Technetium-99m	p. 143
Iodine-123	p. 144
Conclusion	p. 146
Further reading	p. 149
Glossary	p. 161
Appendix	p. 167
Subject Index	p. 172
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