Semi-syntheses and interrogation of indole-substituted Aspidosperma terpenoid alkaloids.

We demonstrated here a series of Aspidosperma terpenoid alkaloids can be quickly prepared using semisynthesis from naturally sourced tabersonine, featuring multiple oxygen-based substituents on the indole ring such as hydroxy and methoxy groups. This panel of complex compounds enabled the exploration of indole modifications to optimize the indole alkaloids' anticancer activity, generating lead compounds (e.g., with C15-hydroxy, C16-methoxy, and/or C17-methoxy derivatizations) that potently inhibit cancer cell line growth in the single-digit micromolar range. These results can help guide the development of Aspidosperma terpenoid alkaloid therapeutics. Furthermore, this synthetic approach features late-stage facile derivatization on complex natural product molecules, providing a versatile path to indole derivatization of this family of alkaloids with diverse chemical functionalities for future medicinal chemistry and chemical biology discoveries.

Wine astringency reduces flavor intensity of Brussels sprouts.

The bitterness of vegetables is a leading reason why they are avoided by children and some adults. Bitterness is perceived via TAS2R receptors located on the tongue. In contrast, astringency is a mouthfeel rather than a taste, and is perceived as a dry, puckering sensation. To date few reports have suggested any interactions between the two processes even though they often occur simultaneously in many real foods. In this study, we have used Brussels sprouts as an exemplar bitter vegetable and examined the influence of a number of different interventions on perceived intensity. Subjects rated the intensity of Brussels sprouts before and after three interventions: gravy, red wine, and water. Only red wine caused a significant (p < .0001) decrease in VAS scale, from 5.5 to 3.5 on a 10-point labeled magnitude scale. The results suggest the astringency of the red wine affected the perception of bitter in the Brussels sprout. Some possible mechanisms are discussed. PRACTICAL APPLICATIONS: This report reveals a possible insight into how bitterness is perceived in humans. By using astringency to affect salivary proteins, we suggest they may play a role in the detection of bitterness. This may be by helping to transport bitterness compounds to the taste bud receptors or a separate mechanism. Potentially this also opens up new ways to block bitterness.