A Simple Route for Synthesis and Evaluation of Antioxidant Activity of (Guaiazulen-1-yl)furans

An effective protocol for the synthesis of guaiazulene substituted furan derivatives via three-component reactions of guaiazulene, α-ketoaldehyde, and 1,3-dicarbonyl compound under mild conditions in good yield is reported. All of these compounds were evaluated for their antioxidant properties in vitro against lipid peroxidation and several compounds were found to have good activities. Polysubstituted furans are among the most important heterocyclic compounds with widespread occurrence in nature. Compounds featuring a furan skeleton exhibit diverse biological properties, such as anticancer, anti-inflammatory, anti-allergic, hair-growth-stimulating and immunosuppressive activities. Furthermore, many polysubstituted furans have been widely used as important reaction intermediates in the total synthesis and synthetic industry. Guaiazulene is a known active component of the essential oil of Guaiacum officinalis L., and there are a number of reports describing the anti-allergenic and anti-inflammatory activities. Azulene derivatives have attracted interest in medicine as antiulcer drugs, anticancer agents, and as antioxidant therapeutics for neurodegenerative conditions. A variety of heterocycle-fused and substituted azulenes have so far been obtained on the viewpoints of chemical properties and physiological activities by several methods. In recent years, our reserach group has reported the synthesis of new heteroarylazulene derivatives. As part of a continuing effort in our laboratory toward the development of azulene chemistry, we became interested in exploring the reactivity and synthetic application of guaiazulene to guaiazulene substituted furan derivatives via multicomponent reaction of guaiazulene, α-ketoaldehyde, and 1,3-dicarbonyl HETEROCYCLES, Vol. 102, No. 1, 2021 105