School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda 669-1337, Japan.
Nat Commun. 2014 Mar 24;5:3478. doi: 10.1038/ncomms4478.
Ellagitannins are a family of polyphenols containing more than 1,000 natural products. Nearly 40% of these compounds contain a highly oxygenated diaryl ether that is one of the most critical elements to their structural diversity. Here, we report a unified strategy for the synthesis of highly oxygenated diaryl ethers featured in ellagitannins. The strategy involves oxa-Michael addition of phenols to an orthoquinone building block, with subsequent elimination and reductive aromatization. The design of the building block--a halogenated orthoquinone monoketal of gallal--reduces the usual instability of orthoquinone and controls addition/elimination. Reductive aromatization is achieved with perfect chemoselectivity in the presence of other reducible functional groups. This strategy enables the synthesis of different diaryl ethers. The first total synthesis of a natural ellagitannin bearing a diaryl ethers is performed to demonstrate that the strategy increases the number of synthetically available ellagitannins.
鞣花单宁是一类含有 1000 多种天然产物的多酚。这些化合物中近 40% 含有一个高度氧化的二芳基醚，这是其结构多样性的最重要因素之一。在这里，我们报告了一种统一的策略，用于合成鞣花单宁中具有高度氧化的二芳基醚。该策略涉及酚与邻醌砌块的氧迈克尔加成，随后消除和还原芳构化。砌块的设计——鞣花酸的卤代邻醌单缩酮——降低了邻醌的通常不稳定性并控制加成/消除。在存在其他可还原官能团的情况下，通过还原芳构化实现了完美的化学选择性。该策略可实现不同二芳基醚的合成。首次完成了带有二芳基醚的天然鞣花单宁的全合成，证明了该策略增加了可合成鞣花单宁的数量。
