Reaction coupling separation for isosteviol production from stevioside catalyzed by acidic ion-exchange resin

Isosteviol, a prodrug used to be obtained via Wagner-Meerwein rearrangement from steviol with low yield and long reaction time. Herein, an in-situ separation-coupling-reaction is presented to prepare isosteviol from the natural sweetener stevioside. Simply with in-situ water-washing, the product containing 92.98% purity of isosteviol was obtained with a stevioside conversion of 97.23% from a packet bed reactor without further separation. Within the assayed inorganic acid, organic acids and acidic ionic liquids, the acidic ion-exchange resins provided higher product specificity towards isosteviol. Furthermore, comparing to 5-Fluorouracil, the product presented similar and even stronger inhibition on proliferation of the assayed human cancer cells in a time and dose-dependence by causing cell phase arrest. Isosteviol treatment caused G1 arrest on SGC-7901, HCT-8 and HCT-116 cells, S arrest on HepG2, Huh-7 and HepG3B cells, and G2 arrest on MGC-803 cells, respectively. Graphic abstract Reaction coupling separation for isosteviol production catalyzed by acidic ion-exchange resin.

Automated summary

Isosteviol can be efficiently prepared from stevioside using an in-situ separation-coupling-reaction method, which shows promising inhibition effects on tumor cells. Acidic ion-exchange resins demonstrate higher specificity for isosteviol production compared to other acids and ionic liquids.