Chiroptical study and absolute configuration of (-)-O-DMA produced from daidzein metabolism

To elucidate the hitherto unknown absolute configuration of (-)-O-desmethylangolensin ((-)-O-DMA), an intestinal bacterial metabolite produced from daidzein, chiroptical study, including specific optical rotation and electronic circular dichroism (ECD), of (R)-O-DMA was carried out by Time-Dependent Density Functional Theory (TD-DFT) calculations. Intramolecular hydrogen bonding between 2'-OH and carbonyl oxygen at 1-C of O-DMA was a governing factor for O-DMA to form the stable conformations. Total energy values of four possible conformers were calculated in the framework of DFT using the B3LYP exchange correlation functional at the 6-31++G basis set level. The theoretical specific rotation and ECD spectra of all conformers in ethanol were obtained by TD-DFT calculation using B3LYP functional at the 6-311++G basis set level, and compared to the experimental data. Chiroptical properties of (R)-O-DMA showed a good agreement with the biological (-)-O-DMA. Therefore, the stereospecific biosynthetic pathway of (-)-O-DMA was proposed as daidzein → (R)-dihydrodaidzein ↔ (S)-dihydrodaizein → (R)-O-DMA.