Fundacao Oswaldo Cruz, Instituto de Tecnologia em Farmacos - Farmanguinhos. Rua Sizenando Nabuco 100, Manguinhos, 21041- 250, RJ, Brazil.
Curr Org Synth. 2020;17(1):3-22. doi: 10.2174/1570179417666191218112842.
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.
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.
The most prominent methodologies for the synthesis of onychines were reviewed.
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 4-azafluorenones.
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.
指甲花碱是一种低浓度的从番荔枝科中分离出来的 4-氮杂菲酮生物碱。指甲花碱及其类似物表现出广泛的药理活性，如抗真菌、抗菌、抗癌和抗疟。由于一些 4-氮杂菲酮衍生物具有很高的生物活性，已经开发了几种合成方法来获取它们。
考虑到这些生物碱的重要性，我们旨在介绍指甲花碱及其衍生物的主要合成方法以及一些 4-氮杂菲酮的生物活性。
综述了指甲花碱合成的最突出方法。
在这项工作中，我们涵盖了指甲花碱和 4-氮杂菲酮衍生物的许多合成方法，包括分子内环化、多组分反应、微波辅助多组分反应、Diels-Alder 反应等。此外，我们还回顾了 4-氮杂菲酮的生物活性。
4-氮杂菲酮已成为药物化学中的重要结构；然而，大多数情况下，获得新的衍生物涉及到有毒的催化剂、苛刻的反应条件和长步骤的程序。因此，开发具有更简单操作、简单纯化程序、高收率和低环境影响的新合成路线是可取的。
