来自伊博加植物的抗上剂的生物合成
Scott C Farrow1, Mohamed O Kamileen1, Lorenzo Caputi1
1Department of Natural Product Biosynthesis , Max Planck Institute of Chemical Ecology , Hans-Knöll-Straße 8 , 07745 Jena , Germany.
Journal of the American Chemical Society
|August 1, 2019
概括
科学家们已经完成了对阿片类药物成治疗的关键化合物 (-) - 沃坎丁和 (-) - 伊波加因的完整生物合成. 这一突破使生物催化生产成为可能,
科学领域:
- 自然产品生物合成
- 医学化学
- 有机化学
背景情况:
- (-) - 伊波加因和 (-) - 沃坎基因是植物性精神活性药物,具有治疗阿片类成的潜力.
- 目前从植物中获取这些化合物具有挑战性,限制了它们的广泛应用.
- 这些类化合物具有与其他相关的天然产品不同的独特的酶体结构.
研究的目的:
- 建立一个完整的生物合成路径 (-) -voacangine.
- 为了使生物催化生产 (-) -voacangine并将其转化为 (-) -ibogaine.
- 研究它们的合成中涉及的反选择性酶机制.
主要方法:
- 实现了 (-) - 沃坎丁的完整生物合成.
- 通过加热生成脱化voacangine,然后转化为 (-) - ibogaine.
- 分析了酶反应以了解酶选择性.
主要成果:
- 成功完成 (-) - 沃坎的生物合成.
- 生物催化生成 (-) - 沃坎丁,并转化为 (-) - 伊波加因.
- 与相关的类化合物相比, (-) - 伊波加因和 (-) - 伏干因的反抗分子构成的证明.
- 对酶选择性形式的迪尔斯-阿尔德反应的洞察.
结论:
- 通过完整的生物合成,可以产生可扩展的 (-) - 沃坎丁和 (-) - 伊波加因.
- 这项工作提供了一种可持续的方法来获得这些有价值的精神活性化合物.
- 这些发现提供了对质纯天然产物的生物合成和酶反应的重要见解.
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