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

High Resolution Image Download MS PowerPoint Slide 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.