The Lignans

Nature has long served as an important source of therapeutics, and lignans represent a large class of pharmacologically active compounds (Cunha et al. 2012). This family of molecules demonstrates a wide range of biological activities, which plants use as a front‐line chemical defence against pathogens (Figure 1.1). Additionally, the anticancer, antimiotic, antiangiogenesis and antiviral properties possessed by lignans have made them appealing drug candidates, as well as starting points for drug discovery. Lignans currently employed for healthcare include (−)‐podophyllotoxin (1), a treatment for warts, and its derivatives (−)‐etoposide (2) and (−)‐teniposide (3), two potent chemotherapeutic agents (Liu et al. 2007). Other members of this class with promising biological activities include (+)‐gomisin J (4) and (+)‐pinoresinol (5). Due to the established benefits of the lignans, both their biosynthesis and synthetic strategies to access them have been areas of extensive research. In addition to their varied biological activities, lignans comprise a vast array of structurally distinct skeletons (Figure 1.2), including 6‐ and 8‐membered carbocycles (6, 7), linear dibenzylbutanes (8), and diversely oxidized tetrahydrofurans (9–11). Remarkably, their biosynthesis originates from a regio‐ and stereoselective, oxidative coupling of relatively simple monolignols (propenyl phenols) (12), to form the key 8–8 bond that serves to characterize all lignan natural products. Subsequent transformations, including cyclization and oxidation of the parent scaffold, convert the initially formed dimer to various family members, imparting unique functionalities. While this blueprint has served as a key source of inspiration for decades of biomimetic synthetic approaches to the lignans, issues of selectivity in the oxidative coupling have led researchers to alternative, target‐oriented routes, which are often specific for an individual structural class. In this review, we summarize these recent efforts from 2009 to 2016, and provide an overview of contemporary research efforts interrogating the lignans. Previous The Lignans