Total Synthesis of Altemicidin: A Surprise Ending for a Monoterpene Alkaloid.
Total Synthesis of Altemicidin: A Surprise Ending for a Monoterpene Alkaloid.
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DOI：
10.1021/jacsau.3c00417
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发表时间：
2023-10-23
期刊：
影响因子：
8
通讯作者：
Maimone, Thomas J
中科院分区：
文献类型：
--
作者：
Harmange Magnani, Claire S;Hernandez-Melendez, Jose R;Tantillo, Dean J;Maimone, Thomas J
单萜生物碱具有独特的化学多样性和广泛的生物活性。它们紧凑的复杂性使它们成为合成目标，并在杂环化学领域激发了许多独特的策略和战术。本文记录了旨在获得不寻常的含磺胺天然产物阿替西丁的合成计划的演变，在我们的整个合成研究中，人们普遍认为阿替西丁是一种单萜生物碱，但最近发现它起源于一种意想不到且完全不同的生物合成途径。通过利用吡啶脱芳构化/环加成策略，我们开发了一种简洁的途径，以5，6-稠合双环氮杂环庚三烯核心，并经过大量的实验，最终合成altemicidin本身。有效地操纵存在于这种高极性支架上的多个官能团的策略被证明是具有挑战性的，但最终通过几次精心策划和化学选择性的转化实现了投资，这些投资以显着更短的化学合成的形式支付红利。令人惊讶的是，我们推测的这种生物碱类的非生物合成策略与随后确定的生物合成途径之间的键形成逻辑惊人地相似。
Monoterpene alkaloids encompass distinct chemical diversity and wide-ranging bioactivity. Their compact complexity has made them popular as synthetic targets and has inspired many distinct strategies and tactics in the field of heterocyclic chemistry. This article documents the evolution of a synthetic program aimed at accessing the unusual sulfonamide-containing natural product altemicidin, which was generally believed to be a monoterpene alkaloid throughout our entire synthetic investigations but has recently been found to originate through an unexpected and quite disparate biosynthetic pathway. By leveraging a pyridine dearomatization/cycloaddition strategy, we developed a concise pathway to the 5,6-fused bicyclic azaindane core and, after significant experimentation, an ultimate synthesis of altemicidin itself. Tactics to productively manipulate the multiple functional groups present on this highly polar scaffold proved challenging but were eventually realized via several carefully orchestrated and chemoselective transformations–investments that paid dividends in the form of significantly shorter chemical synthesis. Surprisingly, the bond-forming logic between our presumed abiotic synthetic strategy to this alkaloid class and its subsequently identified biosynthetic pathway is eerily similar.
影响因子：
5.2
作者：
Krenske, Elizabeth H.;Perry, Emma W.;Jerome, Steven V.;Maimone, Thomas J.;Baran, Phil S.;Houk, K. N.
通讯作者：
Houk, K. N.