Purines 123Adenosine nucleotides are at the heart of energy transfer in many metabolic systems, via the interconversion of adeno-
sine triphosphate (ATP), diphosphate (ADP) and monophosphate (AMP). The cyclic monophosphates cAMP and
cGMP are particularly important as ‘second messengers’, which transfer signals from neurotransmitters such as adrena-
line, and peptide hormones (e.g. glucagon) acting at receptors on the outer surface of cells. The nucleotides are released
from the inner surface of the cell wall to activate systems within the main body of the cell. Inhibitors of enzymes
(phosphodiesterases: PDEs) that catalyse the breakdown of these cyclic phosphates can prolong activity and are a very
important class of drugs, for example sildenafi l (page 175). Adenosine is also a component of a number of co-enzymes
(pages 160–161).
A number of purine nucleoside analogues occur naturally. Some of these involve modifi cation of the purine nucleus,
where a nitrogen is notionally replaced by another atom, for example oxanosine, where N-1 is replaced by oxygen, and
tubercidin, where N-7 is replaced by carbon (this latter system is often referred to informally as a ‘7-de-azapurine’).
Other natural products contain modifi ed ribose moieties, the best-known example probably being aristeromycin,
where the cyclic oxygen is replaced by CH 2. This compound, isolated from a Streptomyces species, can be produced
by fermentation, and is a useful starting material for the synthesis of ‘carba’ nucleosides. Other purine analogues have
been prepared for medicinal chemistry, where further nitrogens replace carbons.
Much of the chemistry of purines, as for pyrimidines, centres on oxy- and amino-compounds (or related derivatives
such as halides) because of the biological importance of these compounds and also their ready availability as starting
materials. This is particularly true of the nucleic acid bases adenine, guanine and hypoxanthine and their correspond-
ing ribosides, adenosine, guanosine and inosine, which are all readily available in quantity, being produced mainly by
fermentation or partial synthesis from fermentation products.
The polyoxy-purine uric acid is also readily available and is easily converted into 2,6,8-trichloropurine, which is a
very useful starting material in which all the free carbons of purine can be manipulated by nucleophilic substitution.
Uric acid, the end product of nucleic acid metabolism in animals, birds and reptiles, was one of the fi rst (heterocyclic)