Three new terpenoids, sterebins O, P1, and P2, isolated from Stevia rebaudiana fermented by Saccharomyces cerevisiae

The diversity of natural compounds is extensive but not unlimited. We therefore studied the feasibility of fermenting plant extracts to increase the diversity of natural compounds for use as drug candidates. Three new terpenoids, sterebins O (1), P1 (2), and P2 (3), were isolated from an extract of Stevia rebaudiana fermented by Saccharomyces cerevisiae. The structures of these compounds were established using NMR, MS, and IR methods. The absolute configuration of 1 was determined by X-ray diffraction analysis, and that of 2 and 3 from the ECD spectrum of their benzoate derivatives. These three compounds were not observed in S. rebaudiana extracts by TLC, suggesting that the compounds were generated during the fermentation process. Compounds 1, 2, and 3 all inhibited melanogenesis in theophylline-stimulated B16 melanoma cells, with 1 exhibiting the lowest IC50 value (9.8 μM). The results indicate that fermentation of plant extracts may provide a route for generating many useful compounds.