SynBioC Research Group, Green Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium.
Chem Rev. 2024 Jun 26;124(12):7907-7975. doi: 10.1021/acs.chemrev.4c00090. Epub 2024 May 29.
The increasing importance of azaheterocyclic phosphonates in the agrochemical, synthetic, and medicinal field has provoked an intense search in the development of synthetic routes for obtaining novel members of this family of compounds. This updated review covers methodologies established since 2004, focusing on the synthesis of azaheterocyclic phosphonates, of which the phosphonate moiety is directly substituted onto to the azaheterocyclic structure. Emphasizing recent advances, this review classifies newly developed synthetic approaches according to the ring size and providing information on biological activities whenever available. Furthermore, this review summarizes information on various methods for the formation of C-P bonds, examining sustainable approaches such as the Michaelis-Arbuzov reaction, the Michaelis-Becker reaction, the Pudovik reaction, the Hirao coupling, and the Kabachnik-Fields reaction. After analyzing the biological activities and applications of azaheterocyclic phosphonates investigated in recent years, a predominant focus on the evaluation of these compounds as anticancer agents is evident. Furthermore, emerging applications underline the versatility and potential of these compounds, highlighting the need for continued research on synthetic methods to expand this interesting family.
氮杂杂环膦酸酯在农业化学、合成和医药领域的重要性不断增加，这促使人们强烈寻求开发合成路线来获得该类化合物的新型成员。本综述涵盖了自 2004 年以来确立的方法，重点介绍了氮杂杂环膦酸酯的合成，其中膦酸酯部分直接取代到氮杂杂环结构上。强调了最新进展，本综述根据环大小对新开发的合成方法进行了分类，并在有可用信息时提供了关于生物活性的信息。此外，本综述总结了形成 C-P 键的各种方法的信息，考察了可持续的方法，如 Michaelis-Arbuzov 反应、Michaelis-Becker 反应、Pudovik 反应、Hirao 偶联和 Kabachnik-Fields 反应。在分析了近年来研究的氮杂杂环膦酸酯的生物活性和应用之后，显然明显关注这些化合物作为抗癌剂的评估。此外，新兴应用强调了这些化合物的多功能性和潜力，突出了需要继续研究合成方法来扩展这一有趣的家族。
