School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China.
Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
Nat Prod Rep. 2022 Sep 21;39(9):1856-1875. doi: 10.1039/d2np00028h.
Covering: up to 2022Podophyllotoxin (PTOX, 1), a kind of aryltetralin-type lignan, was first discovered in the plant and its structure was clarified by W. Borsche and J. Niemann in 1932. Due to its potent anti-cancer and anti-viral activities, it is considered one of the molecules most likely to be developed into modern drugs. With the increasing market demand and insufficient storage of natural resources, it is crucial to expand the sources of PTOXs. The original extraction method from plants has gradually failed to meet the requirements, and the biosynthesis and total synthesis have become the forward-looking alternatives. As key enzymes in the biosynthetic pathway of PTOXs and their catalytic mechanisms being constantly revealed, it is possible to realize the heterogeneous biosynthesis of PTOXs in the future. Chemical and chemoenzymatic synthesis also provide schemes for strictly controlling the asymmetric configuration of the tetracyclic core. Currently, the pharmacological activities of some PTOX derivatives have been extensively studied, laying the foundation for clinical candidate drugs. This review focuses primarily on the latest research progress in the biosynthesis, total synthesis, and pharmacological activities of PTOX and its derivatives, providing a more comprehensive understanding of these widely used compounds and supporting the future search for clinical applications.
截至 2022 年
鬼臼毒素（PTOX，1），一种芳基四氢萘型木脂素，最初在植物中发现，其结构于 1932 年由 W. Borsche 和 J. Niemann 阐明。由于其强大的抗癌和抗病毒活性，它被认为是最有可能开发成现代药物的分子之一。随着市场需求的增加和天然资源储备的不足，扩大 PTOX 来源至关重要。从植物中原始提取方法已逐渐不能满足要求，生物合成和全合成已成为前瞻性选择。随着 PTOX 生物合成途径中的关键酶及其催化机制不断被揭示，未来有可能实现 PTOX 的异质生物合成。化学和化学生物合成也为严格控制四环核心的不对称构型提供了方案。目前，一些 PTOX 衍生物的药理学活性已得到广泛研究，为临床候选药物奠定了基础。
本综述主要关注 PTOX 及其衍生物的生物合成、全合成和药理学活性的最新研究进展，为这些广泛使用的化合物提供更全面的了解，并支持未来对临床应用的探索。
