PRODUCTS

STEVIOL GLYCOSIDE

Steviol glycoside = Kaur-16-en-18-oic acid, 13-[(O-β-D-glucopyranosyl-(1.fwdarw.2)-O-[β-D-glucopyranosyl-(1.fwdarw.3)]-β-D-glucopyranosyl)oxy]-, β-D-glucopyranosyl ester, (4α)-

CAS Number : 58543-16-1
EC Number : 611-696-6
PubChem CID : 6918840
Molecular Formula : C44H70O23
Molecular Weight : 967.0
Melting Point : 242 - 244 °C
Boiling Point : 1103.45 °C. @ 760.00 mm Hg

Steviol glycosides are the chemical compounds responsible for the sweet taste of the leaves of the South American plant Stevia rebaudiana (Asteraceae) and the main ingredients (or precursors) of many sweeteners marketed under the generic name stevia and several trade names.
They also occur in the related species S. phlebophylla (but in no other species of Stevia) and in the plant Rubus chingii (Rosaceae).

Steviol glycosides from Stevia rebaudiana have been reported to be between 30 and 320 times sweeter than sucrose, although there is some disagreement in the technical literature about these numbers.
They are heat-stable, pH-stable, and do not ferment.

Steviol glycosides do not induce a glycemic response when ingested, because humans cannot metabolize stevia.
The acceptable daily intake (ADI) for steviol glycosides, expressed as steviol equivalents, has been established to be 4 mg/kg body weight/day, and is based on no observed effects of a 100 fold higher dose in a rat study.

Structure of Steviol glycoside
These compounds are glycosides of steviol.
Specifically, their molecules can be viewed as a steviol molecule, with its carboxyl hydrogen atom replaced by a glucose molecule to form an ester, and a hydroxyl hydrogen with combinations of glucose and rhamnose to form an acetal.

The steviol glycosides found in S. rebaudiana leaves, and their dry weight percentage, include:

-Stevioside (5–10%)
-Dulcoside A (0.5–1%)
-Rebaudioside A (2–4%)
-Rebaudioside B
-Rebaudioside C (1–2%)
-Rebaudioside D
-Rebaudioside E
-Rebaudioside F
-Rubusoside
-Steviolbioside

The last three are present only in minute quantities, and rebaudioside B has been claimed to be a byproduct of the isolation technique.
A commercial steviol glycoside mixture extracted from the plant was found to have about 80% stevioside, 8% rebaudioside A, and 0.6% rebaudioside C.

The Chinese plant Rubus chingii produces rubusoside, a steviol glycoside not found in Stevia.
According to the EU Stevia Regulation of 13 July 2021, however, rubusoside is one of the eleven major glycoside components of Stevia, extracted from the leaves of the Stevia rebaudiana.

Steviol glycoside and rebaudioside A were first isolated in 1931 by French chemists, Bridel and Lavielle.
Both compounds have only glucose subgroups: stevioside has two linked glucose molecules at the hydroxyl site, whereas rebaudioside A has three, with the middle glucose of the triplet connected to the central steviol structure.

Early sensory tests led to claims that rebaudioside A was 150 to 320 times sweeter than sucrose, stevioside was 10 to 270 times sweeter, rebaudioside C 40 to 60 times sweeter, and dulcoside A 30 times sweeter.
However, a more recent evaluation found Steviol glycoside to be about 240 times sweeter, and stevioside about 140 times.
Steviol glycoside also had the least bitterness and aftertaste.
The relative sweetness seems to vary with concentration: a mix of steviol glycosides in the natural proportions was found to be 150 times sweeter than sucrose when matching a 3% sucrose solution, but only 100 times sweeter when matching a 10% sucrose solution.

Biosynthesis of Steviol glycoside
In Stevia rebaudiana, the biosynthesis of the glucosides occurs only in green tissues.
Steviol is first produced in the plastids and in the endoplasmic reticulum is glucosylated and glycosylated in the cytoplasm, catalyzed by UDP-glucosyltransferases.
Steviol glycoside, in particular, is formed from stevioside.

Though there are several molecules that fall into the category of steviol glycoside, synthesis follows a similar route.
Synthesis of steviol glycoside begins with isoprene units created via the DXP or MEP pathway.
Two molecules derived from primary metabolism, Pyruvate and Glyceraldehyde 3-Phosphate, are the initial molecules for this pathway.

Upon forming IPP and DMAPP, the diterpene GGPP is formed by via head-to-tail addition by an Sn1 mechanism.
Elongation begins when IPP and DMAPP form Geranyl Pyrophosphate (GPP).
GPP elongates through the same Sn1 mechanism to create Farnesyl Pyrophosphate (FPP), and FPP elongates to form GGPP.
With the formation of GGPP cyclization occurs by enzymes copalyl diphosphate synthase (CDPS) and Kuarene Synthase (KS) to form -(-)Kuarene.

Several oxidation steps then occur to form steviol.
Steviol glycoside biosynthesis then follows several modifications from steviol that regioselectively select for sugar molecules to be placed.
Once these molecules are fully glycosylated, the glycosides are then stored in vacuoles.

Steviol glycoside is a rebaudioside that is rubusoside in which the hydroxy groups at positions 3 and 4 of the beta-D-glucopyranosyloxy group at the 13alpha position have both been converted to the corresponding beta-D-glucopyranoside.
Steviol glycoside has a role as a sweetening agent.
Steviol glycoside is a beta-D-glucoside, a tetracyclic diterpenoid and a rebaudioside.
Steviol glycoside is functionally related to a rubusoside and a beta-D-Glcp-(1->2)-[beta-D-Glcp-(1->3)]-beta-D-Glcp.

Steviol glycoside is a natural product found in Stevia rebaudiana and Bos taurus with data available.

Methods of Manufacturing of Steviol glycoside
Stevioside can be isolated from the leaves of Stevia by extraction with water or water - ethanol mixtures.
Crude Stevia extracts are more or less purified, e.g., by treatment with calcium or magnesium hydroxides or carbonates.
Further purification by ion-exchangers, or absorption of undesired ingredients is possible.
Stevioside can be obtained from the extracts by precipitation with methanol.

Steviol glycoside is isolated from Stevia leaves in a similar way to stevioside.
The ratio of rebaudioside A to stevioside can be increased by extraction with methanol, and further purification with column chromatography yields rebaudioside-A-rich products.
Steviol glycoside can, in addition, be transformed enzymatically to rebaudioside A.
Commercial production routes often fail to yield pure Steviol glycoside or rebaudioside A.

Steviol glycoside has been used as a standard in high performance liquid chromatography (HPLC) for quantification of steviol glycosides.
Stevioside-induced ROS-mediated apoptosis was studied in human breast cancer cells.
Rebaudioside-A is a steviol glycoside responsible for the sweet taste of the leaves of the stevia plant.
These compounds range in sweetness from 300 times sweeter than sucrose.

Steviol glycoside is heat-stable, pH-stable, does not ferment, and does not induce a glycemic response when ingested, thus making them attractive as natural sweeteners to diabetics and others on carbohydrate-controlled diets.
Steviol glycoside has recently been shown potently stimulates the insulin secretion, and this insulinotropic effect of rebaudioside-A has been shown to be mediated via inhibition of ATP-sensitive K(+)-channels and requires the presence of high glucose.

Steviol glycoside, a modern natural sweetener extracted from stevia, is also be named as stevia sugar.
Steviol glycoside features high sweetness and low calorie and its sweetness is 200-350 times of that of cane sugar but its calorie is only 1/300 of that of cane sugar.
A large number of pharmaceutical tests have proved that stevioside has no side effects, carcinogens, and is safe for eating.
Constant use can prevent such illnesses as hypertension, diabetes, obesity, heart disease and carious teeth.
Steviol glycoside is an extremely ideal sweetener that can replace cane sugar.

Functions and Applications of Steviol glycoside
1. Steviol glycoside can be widely used in such industries as food, beverage, medicine, daily chemicals, brewery and cosmetics.

2. Steviol glycoside is a new sugar source with broad perspective for development.

3. Steviol glycoside is the natural low-hot sweet agent mostly similar to the flavor of cane sugar, approved to be used by State Ministry of Health and Ministry of Light Industry.

4. Steviol glycoside is the third natural succedaneum of cane sugar and beet sugar with development and health care value, extracted from the leaves of the herbal vegetable of the composite family-stevia rebaudianum.

Steviol glycoside is a sweet tasting medicinal herb; its leaves are rich source of sweetener "steviosides", which are up to three hundred times sweeter than sucrose, more than half of which is composed by Stevioside and Rebaudioside.
Due to its sweet taste it has high commercial value throughout the world as sugar substitute in medicine, foods products and beverages.
The increased market share of Steviol glycoside sweeteners has established a lasting increase in the demand for constant high quality and high purity of Stevia products.
Clinical examinations performed on Steviol glycosides have shown that it is non toxic and exert hypotensive, cardiotonic, anti-diabetic, anti-carcinogenic, anti-inflammatory, anti-viral and anti-bacterial actions.

Steviol glycoside leaves, steviosides and highly refined extracts of the leaves are now officially used as a low calorie natural sweetener and dietary supplement in many countries.
In future, there is possibility that Steviol glycoside could become a major source of high potency low calorie sweetener for growing demand in natural food market.
This manuscript focuses on the phytochemistry, medicinal applications, pharmaco kinetics and safety evaluations of Stevia products.
Besides this, recent developments in agricultural breeding, biotechnological approaches through cell and tissue culture, improved extraction procedures and biotransformation for taste improvement in S. rebaudiana have also been discussed.
Future prospects for realization of commercial production of Steviol glycosides are critically evaluated.

Steviol glycosides are a group of highly sweet diterpene glycosides isolated in only a few plant species of the Paraguayan shrub Stevia rebaudiana.
Steviol glycoside and rebaudioside A are the most abundant steviol glycosides which are responsible for its sweet taste and have commercial value all over the world as sugar substitute in foods, beverages, or medicines.

First-aid measures of Steviol glycoside

Eye Contact :
Rinse immediately with plenty of water, also under the eyelids, for at least 15 minutes.
Get medical attention.

Skin Contact :
Wash off immediately with plenty of water for at least 15 minutes.
Get medical attention immediately if symptoms occur.

Inhalation :
Remove to fresh air.
Get medical attention immediately if symptoms occur.

Ingestion :
Clean mouth with water and drink afterwards plenty of water.
Get medical attention if symptoms occur.

Substance identity

EC / List no.: 611-696-6
CAS no.: 58543-16-1
Mol. formula: C44H70O23

Hazard classification & labelling of Steviol glycoside
According to the notifications provided by companies to ECHA in REACH registrations no hazards have been classified.

About Steviol glycoside
Steviol glycoside is registered under the REACH Regulation and is manufactured in and / or imported to the European Economic Area, at ≥ 1 to < 10 tonnes per annum.
Steviol glycoside is used in articles, by professional workers (widespread uses), in formulation or re-packing and at industrial sites.

Consumer Uses of Steviol glycoside
ECHA has no public registered data indicating whether or in which chemical products the substance might be used.
ECHA has no public registered data on the routes by which Steviol glycoside is most likely to be released to the environment.

Article service life of Steviol glycoside
Other release to the environment of Steviol glycoside is likely to occur from: indoor use in long-life materials with low release rate (e.g. flooring, furniture, toys, construction materials, curtains, foot-wear, leather products, paper and cardboard products, electronic equipment).
ECHA has no public registered data indicating whether or into which articles the substance might have been processed.

Widespread uses by professional workers of Steviol glycoside
Steviol glycoside is used in the following products: cosmetics and personal care products.
Steviol glycoside is used for the manufacture of: chemicals.
Other release to the environment of Steviol glycoside is likely to occur from: indoor use.

Formulation or re-packing of Steviol glycoside
Steviol glycoside is used in the following products: cosmetics and personal care products.
Release to the environment of Steviol glycoside can occur from industrial use: formulation of mixtures.

Uses at industrial sites of Steviol glycoside
Steviol glycoside is used in the following products: cosmetics and personal care products.
Steviol glycoside is used for the manufacture of: chemicals.
Release to the environment of Steviol glycoside can occur from industrial use: in the production of articles.

Manufacture of Steviol glycoside
ECHA has no public registered data on the routes by which Steviol glycoside is most likely to be released to the environment.

Synonyms:
Rebaudioside A
58543-16-1
Stevioside A3
Rebaudioside-A
Truvia
Sweetener 4G-S
Reb A
Reb-A
REBAUDIOSIDEA
Reb-A 97
UNII-B3FUD0528F
B3FUD0528F
19-O-beta-glucopyranosyl-13-O-(beta-glucopyranosyl(1-2)-beta-glucopyranosyl(1-3))-beta-glucopyranosyl-13-hydroxykaur-16-en-19-oic acid
19-O-beta-glucopyranosyl-13-O-(beta-glucopyranosyl(1-2)-beta-glucopyranosyl(1-3))-beta-glucopyranosylsteviol
Stevia Powder
Stevia
Pure Via
Glycoside A3
Chrysanta AR-P
CCRIS 6119
DTXSID8047898
SCHEMBL19769999
SG 95RA50
CHEBI:145012
RA 95
HY-N0466
Rebaudioside A, >=96% (HPLC)
C44H70O23
MFCD02183463
s3796
Glycoside A3, from Stevia rebaudiana
AKOS037748820
ZINC242498440
CCG-270597
CS-5793
DB15136
AS-18742
Rebaudioside A, analytical reference material
X1217
Q63408635
Rebaudioside A, United States Pharmacopeia (USP) Reference Standard
[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] (1R,4S,5R,9S,10R,13S)-13-[(2S,3R,4S,5R,6R)-5-hydroxy-6-(hydroxymethyl)-3,4-bis[[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy]oxan-2-yl]oxy-5,9-dimethyl-14-methylidenetetracyclo[11.2.1.01,10.04,9]hexadecane-5-carboxylate
1-O-(13alpha-{[beta-D-glucopyranosyl-(1->2)-[beta-D-glucopyranosyl-(1->3)]-beta-D-glucopyranosyl]oxy}-18-oxo-5beta,8alpha,9beta,10alpha-kaur-16-en-18-yl)-beta-D-glucopyranose
13-[(2-O-beta-D-glucopyranosyl-3-O-beta-D-glucopyranosyl-beta-D-glucopyranosyl)oxy]-ent-kaur-16-en-19-oic acid beta-D-glucopyranosyl ester
Kaur-16-en-18-oic acid, 13-[(O-β-D-glucopyranosyl-(1.fwdarw.2)-O-[β-D-glucopyranosyl-(1.fwdarw.3)]-β-D-glucopyranosyl)oxy]-, β-D-glucopyranosyl ester, (4α)-
(4α)-13-[(O-β-D-Glucopyranosyl-(1→2)-O-[β-D-glucopyranosyl-(1→3)]-β-D-glucopyranosyl)oxy]kaur-16-en-18-oic Acid β-D-Glucopyranosyl Ester
1-O-(13α-{[β-D-glucopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→3)]-β-D-glucopyranosyl]oxy}-19-oxo-5β,8α,9β,10α-kaur-16-en-19-yl)-β-D-glucopyranose
13-[(2-O-β-D-Glucopyranosyl-3-O-β-D-glucopyranosyl-β-D-glucopyranosyl)oxy]kaur-16-en-18-oic acid β-D-glucopyranosyl ester
13-[(2-O-β-D-glucopyranosyl-3-O-β-Dglucopyranosyl-β-D-glucopyranosyl)oxy]kaur-6-en-8-oic acid, β-Dglucopyranosyl ester
Kaur-16-en-18-oic acid, 13-[(O-β-D-glucopyranosyl-(1.fwdarw.2)-O-[β-D-glucopyranosyl-(1.fwdarw.3)]-β-D-glucopyranosyl)oxy]-, β-D-glucopyranosyl ester, (4α)-
Rebaudioside A
Steviol Glycoside
Stevia 98
13-[(2-O-β-D-glucopyranosyl-3-O-β-Dglucopyranosyl-β-D-glucopyranosyl)oxy]kaur-6-en-8-oic acid, β-Dglucopyranosyl ester
58543-16-1