Approaches toward the Separation, Modification, Identification and Scale up Purification of Tetracyclic Diterpene Glycosides from Stevia rebaudiana (Bertoni) Bertoni

Abstract

Stevia rebaudiana (Bertoni) Bertoni is a plant species native to Brazil and Paraguay well-known by the sweet taste of their leaves. Since the recognition of rebaudioside A and other steviol glycosides as generally recognized as safe by the United States Food and Drug Administration in 2008 and grant of marketing approval by the European Union in 2011, the species has been widely cultivated and studied in several countries. Several efforts have been dedicated to the isolation and structure elucidation of minor components searching for novel non-caloric sugar substitutes with improved organoleptic properties. The present review provides an overview of the main chemical approaches found in the literature for identification and structural differentiation of diterpene glycosides from Stevia rebaudiana: High-performance Thin-Layer Chromatography, High-Performance Liquid Chromatography, Electrospray Ionization Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy. Modification of diterpene glycosides by chemical and enzymatic reactions together with some strategies to scale up of the purification process saving costs are also discussed. A list of natural diterpene glycosides, some examples of chemically modified and of enzymatically modified diterpene glycosides reported from 1931 to February 2021 were compiled using the scientific databases Google Scholar, ScienceDirect and PubMed.

Ready Biodegradability study and insights with ultra‐high‐performance liquid chromatograph coupled to a quadrupole time of flight of a Metformin‐based drug and of Metarecod, a natural substance‐based medical device

“…Their spectral data (Figure 3‐SI) showed typical fragmentation pattern obtained by glycoside bond cleavage. According to published data, 31 the monosaccharide at C‐19 position (ester portion) of our compounds cleave easily thus supporting the presence of the deprotonated molecule [M‐H] − , in the MS spectrum, and the product ion [M‐H‐162] − in the MS/MS spectrum.…”

Fine-Scale Characterization of Plant Diterpene Glycosides Using Energy-Resolved Untargeted LC-MS/MS Metabolomics Analysis

“…The structural diversity of diterpene glycosides, particularly in S. rebaudiana , presents a significant challenge for their fine-scale characterization. , Glycosylation, a common modification, plays a crucial role in determining the bioactivity and functionality of diterpenoid compounds. Steviol glycosides in S. rebaudiana typically contain 1 or 2 glycans with 1–9 sugar units linked to ent-kaurene aglycones.…”

“…The structural diversity and complexity arise from differences in glycan moiety composition, length, and connectivity, as well as variations in corresponding aglycones . Previous studies have delved into the deep phytochemical investigation and chemical diversity of diterpene glycosides in S. rebaudiana . ,,, However, the characterization and distinction of these glycosides, their isomers, and structurally related compounds remain difficult. Analytical methods for diterpene glycoside analysis need to be developed to meet legislative requirements, ensure comprehensive coverage of detected steviol glycosides (including isomers , ), and provide accurate structural annotation .…”

Natural and low‐caloric rebaudioside A as a substitute for dietary sugars: A comprehensive review

“…Steviol, an ent‐kaurene‐type diterpene, is the aglycone of SvGls (Figure 1d). The main structural differences are the number of sugar units linked to the aglycone at positions C 13 ‐ and C 19 ‐, and the different arrangements described (Perera & McChesney, 2021). Rebaudioside A and stevioside are the best known and most abundant among SvGls.…”