Background: Onychine is a 4-azafluorenone alkaloid isolated from the Annonaceae family, in low
concentrations. Onychine and its analogs exhibit a wide range of pharmacological activities such as antifungal,
antibacterial, anticancer, and antimalarial. Because of the high bioactivity of some 4-azafluorenone derivatives,
several synthetic methods have been developed for their procurement.
Objective: Considering the importance of these alkaloids, we aim to present the main synthetic approaches to
onychines and its derivatives and the biological activity of some 4-azafluorenones.
Methods: The most prominent methodologies for the synthesis of onychines were reviewed.
Results: In this work, we cover many synthetic approaches for the synthesis of onychine and 4-azafluorenone
derivatives including intramolecular cyclizations, multicomponent reactions, microwave-assisted multicomponent
reactions, Diels-alder reactions, among others. Moreover, we also review the biological activity of
Conclusion: 4-azafluorenones have risen as prominent structures in medicinal chemistry; however, most of the
time, access to new derivatives involves toxic catalysts, harsh reaction conditions, and long-step procedures.
Therefore, the development of new synthetic routes with more operational simplicity, simple purification
procedure, good yields, and low environmental impact, is desirable.