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Medicinal chemistry and drug research require diverse chemical components to meet strict requirements not only in terms of physical and chemical properties but also in terms of chemical reactivity.
The chemists use the 'build–couple–pair' strategy of organic synthesis, which entails preparing molecular building blocks that contain several chemical groups.
The chemical building block (CBB) is a molecule which can be converted to various secondary chemicals and intermediates, and, in turn, into a broad range of different downstream uses.
Purines comprise an important family of aromatic heterocyclic compounds with a bicyclic structure, which contains a six membered pyrimidine ring fused with a five membered imidazole ring on the side (Fig 1). They are common scaffolds in the biologically and pharmacological compounds, offering potential application in medicinal synthesis. It is noteworthy that purines mainly exist in the human body in the form of purine nucleotides, which play a valuable role in energy supply, metabolic regulation and coenzyme formation.
Fig.1. purine compounds
Unmodified purines are water-soluble, because the bicyclic rings possess four nitrogen atoms that can form stable hydrogen bond with water molecules, advancing its dissolution in water. The presence of conjugated rings in purines promote absorption in UV region and bring the property of light sensitive. Most purines exhibit high boiling point and high melting point, thus they are commonly presented as white crystal. All purines possess secondary amine group as a major reaction site, which can be applied in post-modification. They can react with carboxylic acid to produce acid amides and participate in N-methylation to produce corelative tertiary amines. Besides, secondary amine groups are the key active functional groups of modern medicines and daily food, facilitating the fabrication of many natural products and bioactive molecules with purine motif.
Purine compounds have been detected in various natural medicinal molecules, motivating the synthesis of artificial derivatives to fabricate biologic precursors, which possess excellent pharmacological and physiological activities, such as antibacterial, antidiabetic, antiparasitic, anti-tumor and anti-inflammatory behavior, etc. For example, the antiparasitic activity of the purine analogues can be optimized by adjusting different functional groups (Fig 2).
Fig.2. Chemical structure of antiparasitic purine derivatives. (Expert Opin. Ther. Pat. 2005, 15, 987-994.)
As the genetic material of an organism, DNA (DeoxyriboNucleic Acid) is responsible for guiding protein synthesis and controlling metabolic process, thus DNA play a particularly important role in sustaining the growth of organisms. Purine group has been reported to incorporate into specific positions of DNA, promoting metabolic pathways in DNA diagnostics and treatment (Fig 3).
Fig.3. Metabolic pathways of purine derivatives (Trends Biochem. Sci. 2017, 42, 141-154.)
It is well known that most vegetables and meat contain purine analogues, which can be absorbed by human organ. Scientists have studied the metabolic process in plants and found that purine compounds exist in various alkaloids to promote the growth of plants (Fig 4).
Fig.4. Metabolic process of purine compounds in plants (Phytochemistry 2018, 147, 89-124.)