Ricerc@Sapienza

The functionalization of the skeletal systems of heterocycles represents a significant goal
for the development of new compounds. The heterocyclic molecule xanthine (3,7-dihydro-1Hpurine-
2,6-dione) is a purine base with a bicyclic ring skeleton and four different nitrogen atoms,
three of them are -NH groups. The principal derivatives are the well known natural methylxanthines
(e.g., caffeine, theophylline and theobromine) that have prominent physiological effects at a very low
dose. The natural methylated xanthines, theophylline, theobromine and caffeine, are present in different
plants such as the tea, cocoa and coffee species. For this reason natural xanthines can be considered
as bio-based and renewable starting materials; their use in organic synthesis is strongly recommended
in order to carry out sustainable chemistry. Essentially, the xanthine scaffold led to the
preparation of numerous compounds very attractive in the pharmaceutical field, and these drugs are
commercialized for a wide range of biological activities. The scope of this mini-review is to consider
the use of natural xanthines as starting material in chemical transformations carried out in organic
solvents, without the intent to be exhaustive of all the synthetically chemical applications. More information
on the chemical and electrochemical reactivity of this structural core in an organic solvent
can be useful for the scientific community. The effectiveness of natural xanthines can be improved
by modifying the structures of these already biologically active compounds.