Synthetic Strategies and Biological Diversity of Biflavonoids: Current Status and Perspective

Biflavonoids are natural or pseudo-natural polyphenolic compounds formed by linking two flavonoid monomers via different bonds. Their unique dimeric structure endows them with broad-spectrum biological activities, establishing them as a core focus in drug development. However, the extremely low abundance and high structural similarity of natural biflavonoids present significant challenges. Consequently, synthetic technology has become a solution to overcome bottlenecks in supplements. The approaches involving chemical synthesis, emerging synthetic strategies, and biosynthesis are employed for the synthesis of different biflavonoids. In this review, we systematically summarize the application of diverse synthetic methods and clarify the extensive biological activities of the biflavonoids. Furthermore, we discuss the current challenges in biflavonoid synthesis and biological applications, as well as providing an outlook on future directions.