The Organic Chemistry of Isotopic Labelling

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Format: Hardcover
Pub. Date: 2011-01-24
Publisher(s): Royal Society of Chemistry
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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 Labellingp. xiii
The Discovery and Detection of Isotopesp. 1
Introductionp. 1
The Discovery of Isotopesp. 2
Early Applications of Isotopically Labelled Compoundsp. 5
The Selection of an Isotopic Labelp. 9
The Detection oflsotopesp. 13
Nomenclaturep. 18
Labelling Compounds with Carbon-13 and Carbon-14p. 20
Introductionp. 20
Carbon Labelling Using the Cyanide Jonp. 21
Organometallic Reagents in Carbon Labellingp. 24
The Wittig Reaction in Carbon Labellingp. 27
Carbonyl Condensation Reactions in Carbon Labellingp. 28
The Synthesis of Carbon-labelled Mevalonic Acidp. 31
Aromatic Compounds Labelled in the Ringp. 33
Ring-labelled Heterocyclic Compoundsp. 35
Biosynthetic Methods of Carbon Labellingp. 38
Labelling with Deuterium and Tritiump. 40
Introductionp. 40
The Kinetic Isotope Effectp. 41
The Isolation of Deuterium and Tritiump. 42
Exchange Reactions in Deuterium and Tritium Labellingp. 43
Heteroatom X-H Exchange Reactionsp. 44
General C-H Exchange Reactionsp. 44
Site-specific C-H Exchange Reactionsp. 45
Exchange Reactions of Carbonyl Compoundsp. 49
Exchange Reactions in the Preparation of Some Deuteriated Solventsp. 51
Decarboxylation Reactions in Deuterium and TritiumLabellingp. 51
Reduction Reactionsp. 52
Reducing Agentsp. 52
The Reduction of Carbonyl Groupsp. 54
The Hydrogenolysis of Aliphatic Substituentsp. 54
The Catalytic Reduction of Alkenes and Alkynesp. 54
The Hydrogenolysis of Aryl Halidesp. 56
The Reduction of Iminium Saltsp. 58
The Hydrogenolysis of Organometallic Compoundsp. 58
Hydroborationp. 59
Deuterium- and Tritium-labelled Alkyl Halidesp. 60
Stereochemical Aspects of Labelling with Hydrogen Isotopesp. 62
Introductionp. 62
The Application of the Cahn-Ingold-Prelog Sequence Rules to Labelled Compoundsp. 63
The Stereochemistry of Reactions Used in Labellingp. 64
Labelled Steroidsp. 69
Labelled Gibberellin Plant Hormonesp. 73
The Chiral Methyl Groupp. 75
Stereospecifically Labelled Mevalonic Acidp. 78
Stereospecifically Labelled Isopentenyl Diphosphatep. 81
Labelling of 1-Deoxy-D-xylulosep. 83
The Stereochemistry of Hydrogen Transfer from the Nicotinamide Coenzymesp. 84
The Synthesis of Labelled Amino Acidsp. 86
Introductionp. 86
The Synthesis of Racemic Labelled Amino Acidsp. 87
Labelled Enantiopure Amino Acidsp. 89
The Labelling of Some Compounds of Pharmaceutical Interestp. 96
Introductionp. 96
Lidocainep. 97
Non-steroidal Anti-inflammatory Agentsp. 98
Amphetaminesp. 101
Sulfonamidesp. 102
Morphine and Its Relativesp. 103
Galanthaminep. 106
Tropane Alkaloidsp. 107
Tryptamine Derivativesp. 108
Labelling Compounds with the Stable Isotopes of Nitrogen and Oxygenp. 110
Nitrogen-15p. 110
Oxygen-17 and Oxygen-18p. 116
Labelling with Isotopes of Phosphorus, Sulfur and the Halogens122
Phosphorus-32p. 122
Sulfur-34 and Sulfur-35p. 124
Chlorine-36p. 126
Iodine Isotopesp. 126
Labelling Organic Compounds for Diagnostic Imagingp. 129
Introductionp. 129
Positron Emission Tomographyp. 129
Carbon-11 in PETp. 131
Fluorine-18 in PETp. 135
Nitrogen-13 in PETp. 141
Oxygen-15 in PETp. 141
Isotopes of Brominep. 141
Positron-emitting Metallic Isotopes in PETp. 142
Single Photon Emission Computed Tomographyp. 143
Technetium-99mp. 143
Iodine-123p. 144
Conclusionp. 146
Further readingp. 149
Glossaryp. 161
Appendixp. 167
Subject Indexp. 172
Table of Contents provided by Ingram. All Rights Reserved.

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