1. ARTIFICIAL SWEETNERS
HASEEB HAKKIM
MS10081
IISER MOHALI

2. Sweetness is one of the five basic tastes and is universally regarded as
a pleasurable experience . A great diversity of chemical compounds, such
as aldehydes and ketones are sweet. Among common biological substances, all of the
simple carbohydrates are sweet to at least some degree.
Sucrose (table sugar) is the prototypical example of a sweet substance. Sucrose in solution
has a sweetness perception rating of 1, and other substances are rated relative to this. For
example, another sugar, fructose, is somewhat sweeter, being rated at 1.7 times the
sweetness of sucrose. Some of the amino acids are mildly sweet: alanine, glycine,
and serine are the sweetest. Foods rich in simple carbohydrates such as sugar are those most
commonly associated with sweetness, although there are other natural and artificial compounds
that are sweet at much lower concentrations, allowing their use as non-caloric sugar substitutes .
Some other amino acids are perceived as both sweet and bitter.
Lugduname is the sweetest chemical known.
It is 2,00,000 to 3,00,000 times sweeter than
sucrose.

3. Two types of sugar substitutes are available: Bulk and Intense.
Intense sweeteners are artificial sweeteners, synthesized from a variety of starting
materials. These sweeteners are intense due to their sweetness being hundreds,
sometimes thousands times sweeter than that of sucrose, and their mode of action on
the sweet taste bud are all similar. However, there are some clear distinctions as to their
mode of action within the body.
Many bulk sweeteners have the same caloric values as sucrose, but are chosen for
financial reasons/motives. Polyols, or sugar alcohols, lead the list of most common sugar
replacements, although many have a fraction of the sweetness of sucrose, along with
some other less desirable characteristics; the leader being their laxative effects.
Sugar substitute is the broad term used to describe any substance that
replaces sugar (sucrose) as a sweetener in a food item . A sugar substitute could either
be from a natural source or artificially derived. Artificial sweeteners are basically
considered non-caloric. They offer a great trade-off for diabetics or individuals trying to
reduce sugar and/or calories in their diet by giving the sweetness without the
carbohydrates or calories. They are widely used in baked goods, soft drinks, powdered
drink mixes, candy, puddings, canned foods, jams and jellies, dairy products, and
numerous other foods and beverages.

4. Sugar substitutes are used for a number of reasons, including:
To assist in weight loss – Replacing high-energy sugar or corn syrup with other
sweeteners having little or no food energy allows us to eat the same foods we normally
would, while allowing them to lose weight and avoid other problems associated with
excessive caloric intake.
Dental care – sugar substitutes are tooth-friendly, as they are not fermented by
the microflora of the dental plaque. An example of a sweetener that can benefit dental
health is xylitol. Xylitol works to prevent bacteria from adhering to the tooth surface,
thus preventing plaque formation and eventually decay. The carbohydrates and sugars
consumed usually adheres to the tooth enamel. Bacteria can feed upon this food source,
converting it to acid waste that in turn decays the tooth structure. Xylitol cannot be
fermented by these bacteria, so the bacteria have difficulty thriving, thus helping to
prevent plaque formation.
Diabetes mellitus – People with diabetes have difficulty regulating their blood
sugar levels. By limiting their sugar intake with artificial sweeteners, they can enjoy a
varied diet while closely controlling their sugar intake. Also, some sugar substitutes do
release energy, but are metabolized more slowly, potentially allowing blood sugar levels
to remain more stable over time.

5. Reactive hypoglycemia – Individuals with reactive hypoglycemia will produce an
excess of insulin after quickly absorbing glucose into the bloodstream. This causes
their blood glucose levels to fall below the amount needed for proper body and brain
function. As a result, like diabetics, they must avoid intake of high-glycemic foods like
white bread, and often choose artificial sweeteners as an alternative.
Avoiding processed foods – individuals may opt to substitute refined white sugar
with less-processed sugars, such as fruit juice or maple syrup.
Cost – many sugar substitutes are cheaper than sugar. Alternative sweeteners are
often low in cost because of their long shelf-life and high sweetening intensity. This
allows alternative sweeteners to be used in products that will not perish after a short
period of time.
The long-term costs and risks of using artificial sweeteners -- weight gain, diabetes
type II, and desensitization of gustatory (taste) sense -- outweigh this alleged benefit,
however.

6. HOW TASTE WORKS ?
The tongue is covered with papillae - within the
papillae are the taste buds. The taste buds are
actually small groups of epithelial cells forming a
complex interactive unit comprised of 50-150
neural receptors. These receptors are sensitive to
the electrophysiological characteristics of sweet
molecules ; particularly the highly polar regions of
the sugar molecule making for the strong
association between sugars and sweetness.
Glucose specifically binds to the hetero dimeric
receptors, T1R2 and T1R3, which recognize both
natural and synthetic sweeteners. After this
binding there is a series of neural firings in the
brain that evokes memory retention about the
sweetness.
It is these same receptors that molecules of artificial sweeteners are triggering as well. They are
most effective at lower concentrations, which correspond well to packaging due to their intense
perception of sweetness. However, at higher concentrations some molecules can also bind to
another taste receptor, the TRPV1 receptor, which triggers the bitter and sometimes metallic
aftertaste associated with some of the artificial sweeteners.

7. Human T1R2-T1R3 sweet receptor – Binding for most
sweet ligands occurs on the T1R2 unit. Sugars may
interact with the large N termini of both T1R2 and T1R3.
The first prominent theory dealing
with chemical reception for
sweetness proposed that in order
to be sweet, a compound must
contain a hydrogen bond donor
(AH) and a Lewis base (B)
separated by about 0.3
nanometers . “According to this
theory, the AH-B unit of a
sweetener binds with a
corresponding AH-B unit on the
biological sweetness receptor to
produce the sensation of
sweetness.”
As further research developments are taken with these artificial, intense sweeteners
the conformation of these molecules are studied to determine which specific
characteristics are utilized in the distinction of sweetness.

8. Sweeteners that are currently approved by the Food and Drug Administration
(FDA) include:

9. Saccharin , the first artificial sweetener, was discovered serendipitously, as
were most artificial sweeteners. In 1879, Constantine Fahlberg was researching
the oxidation mechanisms of toluene sulfonamide while working at Johns
Hopkins University in the laboratory of Ira Remsen. During his research, a
substance accidentally splashed on his finger; he later licked his finger and
noticed the substance had a sweet taste, which he traced back to saccharin .
Since that time, a number of compounds have been discovered and used as food
additives for their sweetener properties. Saccharin has been in use since 1900
and obtained FDA approval in 1970.
.
Saccharin has no calories and is 300 times
sweeter than sugar (FDA, 2006). It is used in
such products as soft drinks, tabletop
sweeteners, baked goods, jams, chewing
gum, canned fruit, candy, dessert toppings,
and salad dressings. It has also found some
applications in cosmetic products, vitamins,
and pharmaceuticals.

10. Synthesis of Saccharin, Remsen and Fahlberg method.
Saccharin is formed by an initial reaction between toluene and chlorosulfonic acid. It is then
converted to a sulfonamide with ammonia, then oxidized to a benzoic acid and heated to
form the cyclic imide.

11. Maumee synthesis of Saccharin.
Saccharin can be produced in various ways . In 1950, an improved synthesis was
developed at the Maumee Chemical Company of Toledo, Ohio . In this synthesis ,
anthranilic acid successively reacts with nitrous acid (from sodium nitrite and
hydrochloric acid ) , sulfur dioxide, chlorine, and then ammonia to yield saccharin:
It is are very stable for baking, but have a noticeable aftertaste when used in large
amounts. Biologically, following ingestion, saccharin is not absorbed or metabolized by the
body . It is excreted, unchanged, via the kidneys. Because saccharin is not metabolized, the
FDA considers this compound safe.

12. Acesulfame-K was discovered by accident by German scientists Clauss and
Jensen in 1967 while they were conducting research on then new cyclic group, dihydro-
oxathiaxinone dioxide. It is ideal for tabletop use and is soluble in hot and cold beverages .
An advantage of Acesulfame K is that it does not break down in heat so it can be used in
cooking or baking. It can’t be metabolized or stored in the body and therefore 95% of
the consumed sweetener ends up excreted in the urine.
Acesulfame K synthesis from chlorophenol.
Approved in 1998 by the FDA, it is commonly used in diabetic and low-calorie foods and is
200 times sweeter than sucrose. Also it has been found that the synergistic effect of
acesulfame-K with glucose, fructose, sucrose, and sucralose increases its sweetness
intensity (O’Donnell, 2005).

13. Aspartame was discovered in 1965 by James M. Schlatter at the G.D.
Searle company. To test new anti-ulcer drugs, they had to use a tetrapeptide and to
synthesize this tetrapeptide, one of the steps in the process was to make an intermediate,
aspartyl-phenylalanine methyl ester. Accidentally, a small amount of the compound landed
on the chemist’s hand. Without noticing the compound, the chemist licked his finger and
discovered a sweet taste. After realizing it was from the powder intermediate and
believing it was not likely to be toxic, he again tasted the intermediate and found it was
indeed sweet aspartame. It is an odorless, white crystalline powder that is derived from
the two Amino acids aspartic acid and phenylalanine.
It is about 200 times as sweet as
sugar and can be used as a
tabletop sweetener or in frozen
desserts, gelatins, carbonated soft
drinks, refrigerated and non-
refrigerated ready-to-drink
beverages, hot cocoa mixes, teas,
breath mints and chewing gum.
Aspartame has very little aftertaste
but it tends to denature or lose its
sweet taste when it is heated.

14. Phenylalanine and Aspartic Acid to yield Aspartame.
Treatment of L-phenylalanine with methanol in the presence hydrochloric acid causes an ester
reaction with the acid group on the phenylalanine. The product is the methyl ester of
phenylalanine.
The final goal is to react the methyl ester of phenylalanine with aspartic acid to give the
dipeptide amide structure. A series of reactions is required so that only the acid of the base
amino acid is reacted. The acid group on the side chain is protected so that it does not react.
Two of the components of aspartame (phenylalanine and aspartic acid) are chiral,
which means that they have two isomers that are non-super imposable mirror
images. If the incorrect isomers are used, the aspartame molecule will not have the
correct shape to fit the binding site of the 'sweetness' receptors on the tongue.

15. In the synthesis of aspartame, the starting materials are a racemic mixture (equal quantities of
both isomers) of phenylalanine, and aspartic acid. Only the L isomer of phenylalanine is desired
for use. This L isomer may be separated from the D isomer by a chemical pretreatment,
followed by a reaction with the enzyme porcine kidney acylase. The final separation occurs
with an acidic aqueous and organic extraction, where the L isomer is more soluble in the
aqueous layer and the D isomer is more soluble in the organic layer.

16. MECHANISM :

18. Sucralose is the only non-caloric sweetener made from sugar to produce a sweetener
that has no calories, yet is 600 times sweeter and tastes like sugar. It passes rapidly through
the body virtually unchanged. Because of its stability, it is used in a range of products such as
carbonated soft drinks, low-calorie fruit drinks, maple syrup, canned fruit, low-calorie fruit
drinks, baked goods, sauces, and syrups. It pours, measures, cooks, and bakes like sugar.
Sucralose also can be used as a sweetener in nutritional supplements, medical foods, and
vitamin/ mineral supplements.
Sucralose is a chlorinated sugar and is produced from by a selective multi-step
displacement reaction that starts with cane sugar, three of the hydroxyl groups on the
sugar molecule are replaced by three chlorine atoms.
From Sucrose to Sucralose

19. Neotame is sweeter than some marketed no-calorie sweeteners and is approximately
30-40 times sweeter than Aspartame; 7,000-13,000 times sweeter than sugar. It is quickly
metabolized and fully eliminated by the body via normal biological processes. It is used in
foods and beverages, including, but not limited to, chewing gum, carbonated soft drinks,
refrigerated and non-refrigerated ready-to-drink beverages, tabletop sweeteners, frozen
desserts and novelties, puddings and fillings, yogurt-type products, baked goods, and candies.
It also can be used in both cooking and baking.
Individuals who suffer from Phenylketonuria lack or have insufficient amounts of the
enzyme phenylalanine hydroxylase, required to breakdown phenylalanine. Without the
presence of this enzyme, phenylalanine accumulates. Phenylalanine buildup can
significantly alter human brain function.

20. Neotame is similar to aspartame, but has
an extra branch added to the free amine
group of aspartic acid that prevents its
metabolism to produce phenylalanine
that as previously discussed can cause a
tolerance problem in some people. This
branch, a 3,3- dimethylbutyl group, blocks
the peptide enzyme from catalyzing the
reaction, therefore leaving the Neotame
residue intact and generating a minor
amount of methanol that the body
absorbs. This process yields de - esterified
Neotame , the major metabolite, an
insignificant amount of methanol which are
are eliminated from the body with recovery
in urine and feces within 72 hours .
Upon ingestion, aspartame is hydrolyzed in the intestinal lumen into its components,
aspartic acid, phenylalanine, and methanol. These components are then absorbed into
the blood and each is metabolized. Methanol is quickly absorbed through the stomach and
small intestine mucosa. There methanol is converted into formaldehyde (a known carcinogen).
The methyl ester group is readily removed by enzymes (esterases), either during the intestinal
transit by calcium-dependent pancreatic esterases or after absorption by plasma esterase.

22. Regardless of the studies provided to and provided by the FDA, artificial sweeteners continue
to receive negative press from a variety of public awareness groups. Many of these groups
recommend replacement sweeteners that have a more natural origin and are not synthesized
in chemical laboratories.
Common Sugar Alcohols Used as Food Additives
Sugar alcohols, or polyols, are a popular substitute in baked goods as they are considered a
bulk sugar – having similar volume and texture as sucrose. Polyols are chemical derivatives of
sugars that have an alcohol group (-CH2OH) instead of the aldehyde group (-CHO).

23. CONCLUSION
The FDA regulates artificial sweeteners and sugar alcohols, and both are considered
as GRASB(Generally Recognized as Safe) or approved food additives.
Guidelines for using artificial sweeteners: It is important to note that each
sweetener acts differently when heated and some leave an aftertaste when used in
large amounts. The best way to begin using artificial sweeteners in home cooking is
to read label directions carefully.
Using a naturally occurring ingredient to sweeten your food helps prevent harmful
chemicals from entering your system. There are a range of natural options that
can still be safe for diabetics and can add very little calories to food.

24. REFERENCES
• http://www.sugar.ca/english/educators/sugarscience.cfm
• www.caloriecontrol.org/sweeteners-and-lite
• www.diabetes.org/food-and-fitness/food/what-can-i-eat/sugar-
alcohols.html
• Aspartame Information Center. (2006). Aspartame Information Center
homepage. Retrieved July 1, 2007, from www.aspartame.org .
• “Low-calorie Sweeteners and Other Sugar Substitutes: A Review of the Safety
Issues”. Manfred, Kroger. Kathleen Meister & Ruth Kava. 1995 Broadway, 2nd Floor,
New York, NY 10023-5860
• diabetics – NIH
http://diabetes.niddk.nih.gov/DM/pubs/statistics/index.htm