The iboga enigma: the chemistry and neuropharmacology of iboga alkaloids and related analogs.
The iboga enigma: the chemistry and neuropharmacology of iboga alkaloids and related analogs.
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DOI：
10.1039/d0np00033g
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发表时间：
2021-03-04
影响因子：
11.9
通讯作者：
Olson DE
中科院分区：
文献类型：
--
作者：
Iyer RN;Favela D;Zhang G;Olson DE
很少有几类天然产品能像牛至生物碱那样激励了许多化学家和生物学家。这个单萜类吲哚生物碱家族包括抗成瘾化合物伊波甘和长春花碱，长春花碱是化疗药物长春花碱的前体。尽管人们知道这些小分子已经有120多年的历史了，但它们继续挑战我们关于生物合成途径的假设，催化我们构建复杂建筑的创造力，并鼓励治疗精神疾病的新方法。本文综述了牛黄生物碱的生物合成和化学合成的最新进展，以及它们作为下一代神经疗法的应用。在适当的时候，我们提供过去十年的发现的历史背景，并指出尚未解决的领域。虽然自20世纪60年代以来，在化学和药理方面取得了重大进展，但很明显，在未来的几年里，牛至生物碱将继续推动科学创新。
Few classes of natural products have inspired as many chemists and biologists as have the iboga alkaloids. This family of monoterpenoid indole alkaloids includes the anti-addictive compound ibogaine as well as catharanthine, a precursor to the chemotherapeutic vinblastine. Despite being known for over 120 years, these small molecules continue to challenge our assumptions about biosynthetic pathways, catalyze our creativity for constructing complex architectures, and embolden new approaches for treating mental illness. This review will cover recent advances in both the biosynthesis and chemical synthesis of iboga alkaloids as well as their use as next-generation neurotherapeutics. Whenever appropriate, we provide historical context for the discoveries of the past decade and indicate areas that have yet to be resolved. While significant progress regarding their chemistry and pharmacology has been made since the 1960s, it is clear that the iboga alkaloids will continue to stoke scientific innovation for years to come.