Enantioselective Synthesis of Flavonoids: Dihydroflavonols and Flavan-3-ols

The beneficial role of flavonoids in general and of the proanthocyanidins in particular to mankind is increasingly being recognized. In addition to the multitude of industrial applications, the oligo- and polymeric proanthocyanidins are now also credited for the profound health-promoting effects of tea, fruit juices, and red wine. This is mainly due to their in vitro antioxidant or radical scavenging properties, while the polyflavonoids in red wine have recently been implicated in protection against cardiovascular disorders, e.g., the “French paradox”. These observations highlight the need for synthetic access to enantiopure flavonoid monomeric precursors exhibiting the aromatic oxygenation pattern of the constituent flavanyl units of the naturally occurring proanthocyanidins, hence paving the route to synthesize a representative series of these important biomolecules. This review accordingly focuses on methodologies aimed at the stereoselective syntheses of the different sets of the four diastereomers of both the dihydroflavonols and fiavan-3-ols exhibiting characteristic “natural product” phenolic oxygenation patterns.