Synthesis of Avenanthramide C and Its Analogs Utilizing Classical Condensation, Saponification and Acidification

利用经典缩合、皂化和酸化法合成燕麦酰胺C及其类似物

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Abstract

This work presents a concise and practical synthetic route to the biologically multifunctional avenanthramide C (Avn C, 1a), one of the natural products derived from oats, utilizing three classical organic reactions. Condensation of diacetyl caffeoyl chloride (5) with methyl 5-hydroxyanthranilate (6) in tetrahydrofuran at 80 °C in the presence of pyridine, followed by saponification with 5.0 equiv of lithium hydroxide (3.0 M in H(2)O) in a THF-H(2)O (3:1 v/v) cosolvent system and subsequent acidification to approximately pH 2 using 6.0 M hydrochloric acid, successfully afforded 1a as a pale brown solid in >82% yield and 99% purity. Furthermore, 14 structural analogs of 1a were efficiently synthesized in 60-88% yields by applying the same synthetic strategy.

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