C13-Norisoprenoid megastigmanes: Biosynthesis, classification, natural sources, biological activities, and structure-activity relationship – A comprehensive review

Abstract

C₁₃-Norisoprenoid megastigmanes are a currently expanding class of secondary metabolites originating from the oxidative degradation of carotenoids such as lutein and neoxanthin. These metabolites have been isolated either in free, glycosidically bound forms or as acylated derivatives from a wide diversity of the plant kingdom. The classification of megastigmanes depends on the diversity of the oxygenation positions and the biogenetic origin. These compounds play a crucial role in imparting wine with its characteristic variant flavors, and they are potentially important flavoring agents for the food and pharmaceutical industries. Striking examples for the class are the unusually potent fragrances β-ionone, β-damascenone, and megastigmatrienone. The literature highlighted several compounds that need further development and optimization for drug discovery programs of hepatoprotective, anti-inflammatory, antioxidant, cytotoxic, anti-melanogenic, and cholesterol and triglycerides metabolism-promoting drugs. This comprehensive review focuses on classification, biosynthesis, distribution in natural sources, and chemical structures, the studied biological activities, as well as the structure-activity relationship of the new natural C₁₃-norisoprenoid megastigmanes. A total of 800 C₁₃-norisoprenoid megastigmanes were covered from the first reported isolation of megastigmanes up to December 2024 and 355 references are cited.