Background: Flavonoid is a family of compounds present in the everyday consumption plants
and fruits, contributing to a balanced diet and having health effects. Being a scaffold for new drugs and
presenting a wide range of applicability in illness treatment gives them also an impact in medicine. Among
the several types of flavonoids, flavone and isoflavone derivatives can be highlighted due to their prevalence
in nature and biological activities already established. The standard synthetic route to obtain both halogenated
flavones and isoflavones is through the use of already halogenated starting materials. Halogenation of the
flavone and isoflavone core is less common because it is more complicated and involves some selectivity
Objective: Considering the importance of these flavonoids, we aim to present the main and more recent
synthetic approaches towards their halogenation.
Methods: The most prominent methodologies for the synthesis of halogenated flavones and isoflavones were
reviewed. A careful survey of the reported data, using mainly the Scopus database and halogenation, flavones
and isoflavones as keywords, was done.
Results: Herein, a review has been taken from the latest and more efficient halogenation protocols of
flavones and isoflavones previously built cores. Selective halogenation and the greener methodologies,
including enzymatic and microbial halogenations, were reported. Nevertheless, some interesting protocols
that allowed the synthesis of halogenated flavone and isoflavone derivatives in specific positions using
halogenated reagents were also summarized.
Conclusion: Halogenated flavones and isoflavones have risen as noticeable structures; however, most of the
time, the synthetic procedures involve toxic reagents and harsh reaction conditions. Therefore, the
development of new synthetic routes with low environmental impact is desirable.