Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, China.
Nat Commun. 2024 Jun 22;15(1):5332. doi: 10.1038/s41467-024-49748-2.
Veratramine and cyclopamine, two of the most representative members of the isosteroidal alkaloids, are valuable molecules in agricultural and medicinal chemistry. While plant extraction of these compounds suffers from uncertain supply, efficient chemical synthesis approaches are in high demand. Here, we present concise, divergent, and scalable syntheses of veratramine and cyclopamine with 11% and 6.2% overall yield, respectively, from inexpensive dehydro-epi-androsterone. Our synthesis readily provides gram quantities of both target natural products by utilizing a biomimetic rearrangement to form the C-nor-D-homo steroid core and a stereoselective reductive coupling/(bis-)cyclization sequence to establish the (E)/F-ring moiety.
藜芦碱和环巴胺是同型甾体生物碱中最具代表性的两种成员，它们是农业和药物化学领域的重要分子。由于从植物中提取这些化合物的供应不稳定，因此高效的化学合成方法受到高度需求。在这里，我们从廉价的去氢表雄酮出发，以 11%和 6.2%的总收率，分别展示了藜芦碱和环巴胺的简洁、发散和可扩展的合成方法。我们的合成方法通过生物模拟重排形成 C-去-N-D-同型甾体核心，并采用立体选择性还原偶联/（双）环化序列构建（E）/F-环部分，从而轻松地提供了这两种目标天然产物的克级数量。
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