Ambruticins: tetrahydropyran ring formation and total synthesis
Ambruticins: tetrahydropyran ring formation and total synthesis
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DOI：
10.1039/d1ob00883h
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发表时间：
2021-06-28
影响因子：
3.2
通讯作者：
Willis，Christine L.
中科院分区：
文献类型：
--
作者：
Bowen，James I.;Wang，Luoyi;Willis，Christine L.
鹅膏菌素是一类多酮类天然产物，具有很强的抗真菌活性。基因敲除实验与不饱和3，5-二羟基酸Ambrticin J的环氧化反应形成四氢吡喃环，然后区域选择性环化生成Ambrticin F的观点一致。本文描述了一种收敛的方法，以及不饱和羟基酯的环氧化和环化反应生成四氢吡喃和四氢呋喃的模型研究。全合成包括三个关键片段的制备，它们通过Suzuki-Miyaura交叉偶联和Julia-Kocienski烯化反应得到所需的碳骨架。对三醇的整体去保护和伯醇的选择性氧化，在内酯水解后，得到Ambrticin J。
The ambruticins are a family of polyketide natural products which exhibit potent antifungal activity. Gene knockout experiments are in accord with the proposal that the tetrahydropyran ring of the ambruticins is formed via the AmbJ catalysed epoxidation of the unsaturated 3,5-dihydroxy acid, ambruticin J, followed by regioselective cyclisation to ambruticin F. Herein, a convergent approach to the total synthesis of ambruticin J is described as well as model studies involving epoxidation and cyclisations of unsaturated hydroxy esters to give tetrahydropyrans and tetrahydrofurans. The total synthesis involves preparation of three key fragments which were united via a Suzuki–Miyaura cross-coupling and Julia–Kocienski olefination to generate the required carbon framework. Global deprotection to a triol and selective oxidation of the primary alcohol gave, after hydrolysis of the lactone, ambruticin J.