Jiangsu Key Laboratory of Pesticide Science, and Department of, Chemistry, College of Sciences, Nanjing Agricultural University, 1 Weigang Road, Xuanwu District, Nanjing, 210095, P.R. China.
Department of Pharmaceutical Engineering, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing, 211198, P.R. China.
Chemistry. 2021 Mar 17;27(16):5225-5229. doi: 10.1002/chem.202005098. Epub 2021 Feb 22.
Herein, a divergent synthesis of a variety of 2α- and 5α-substituted furan derivatives from 2-hydroxy-1,4-diones is reported. By using appropriate substrates and an acid catalyst, the reactions occurred selectively through cyclization/1,6-conjugate addition or cyclization/Friedel-Crafts-type cascade reactions. A broad range of nucleophilic reagents (>10 types for the 1,6-conjugate addition for 5α substitution and >20 types for the Friedel-Crafts-type cascade reaction for 2α substitution), including alcohols, amides, furan, thiophene, pyrrole, indole, phenols, and many others, can successfully participate in the reactions, providing a universal strategy for a diversity-oriented synthesis of α-substituted furan derivatives. Deuteriation experiments and DFT calculations were carried out to support the proposed reaction mechanisms. Antifungal activity experiments revealed that products with an indole or 4-hydroxycoumarin core substituted at the 2α position showed moderate activities against Rhizoctorzia solani and Botrytis cinerea, respectively.
本文报道了一种从 2-羟基-1,4-二酮出发，通过发散合成各种 2α-和 5α-取代的呋喃衍生物的方法。通过使用合适的底物和酸催化剂，反应可以通过环化/1,6-共轭加成或环化/Friedel-Crafts 型级联反应选择性发生。一系列亲核试剂（5α 取代的 1,6-共轭加成反应超过 10 种，2α 取代的 Friedel-Crafts 型级联反应超过 20 种），包括醇、酰胺、呋喃、噻吩、吡咯、吲哚、酚等，可以成功参与反应，为α-取代呋喃衍生物的多样性导向合成提供了一种通用策略。氘代实验和 DFT 计算支持了所提出的反应机制。抗真菌活性实验表明，2α 位取代吲哚或 4-羟基香豆素的产物对 Rhizoctorzia solani 和 Botrytis cinerea 分别具有中等的活性。
