Biosynthesis of an Anti-Addiction Agent from the Iboga Plant
Biosynthesis of an Anti-Addiction Agent from the Iboga Plant
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DOI：
10.1021/jacs.9b05999
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发表时间：
2019-08-21
影响因子：
15
通讯作者：
O'Connor, Sarah E.
中科院分区：
文献类型：
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作者：
Farrow, Scott C.;Kamileen, Mohamed O.;O'Connor, Sarah E.
（-）-伊波替尼和（-）-伏冈津是植物衍生的精神活性物质，显示出作为阿片类药物成瘾治疗的前景。然而，这些化合物是由难以获得的植物产生的，使得这些化学品难以大规模使用。在这里，我们报告了（-）-伏冈碱的完全生物合成，和脱酯化伏冈碱，它是通过加热转化为（-）-伊波替尼，使这些化合物的生物催化生产。值得注意的是，与在该天然产物类别中发现的其他主要生物碱相比，（-）-伊波替尼和（-）-伏冈津具有相反的对映异构体构型。因此，这一发现提供了洞察对映选择性酶促正式Diels-Alder反应。
(-)-Ibogaine and (-)-voacangine are plant derived psychoactives that show promise as treatments for opioid addiction. However, these compounds are produced by hard to source plants, making these chemicals difficult for broad-scale use. Here we report the complete biosynthesis of (-)-voacangine, and de-esterified voacangine, which is converted to (-)-ibogaine by heating, enabling biocatalytic production of these compounds. Notably, (-)-ibogaine and (-)-voacangine are of the opposite enantiomeric configuration compared to the other major alkaloids found in this natural product class. Therefore, this discovery provides insight into enantioselective enzymatic formal Diels-Alder reactions.