Reflections on Racemic Natural Products

Racemic natural products with complex molecular structures have inspired chemists for decades. Their widespread occurrence raises interesting biosynthetic questions and poses (retro)synthetic challenges. Using some classic examples and representative work from the recent literature, we show how biomimetic synthesis can address some of these questions and challenges, provide insights into the formation of such molecules in nature, and enable efficient access to them in the laboratory. The importance of stereoselective reaction cascades that involve cycloadditions, electrocyclizations, phenolic oxidations, and Mannich, Michael, and Aldol reactions is highlighted. In the absence of chiral information, these cascades form racemates from achiral precursors. Their stereochemical complexity can be increased further when these racemic products undergo homochiral or heterochiral dimerizations.