E 969

E 969  is a non-caloric artificial sweetener.
E 969  can be used as a table top sweetener and in certain bubblegums, flavored drinks, milk products, jams and confectionery among other things.
E 969  has no notable off-flavors when compared to sucrose and tastes sweet a bit longer than aspartame and is chemically more stable. 

CAS Number : 714229-20-6
Chemical formula :    C24H30N2O7
Molar mass     :      458.511 g·mol−1
Appearance     :  white to yellow powder
Melting point     :  101.5 °C 
Solubility in water    : 0.99 g/L at 25 °C

Preferred IUPAC name :
-(3S)-3-{[3-(3-Hydroxy-4-methoxyphenyl)propyl]amino}-4-{[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino}-4-oxobutanoic acid

Other names :
-N-[N-[3-(3-Hydroxy-4-methoxyphenyl)propyl]-α-L-aspartyl]-L-phenylalanine 1-methyl ester

E 969  is a non-caloric artificial sweetener and aspartame analog by Ajinomoto.
By mass, E 969  is about 20 000 times sweeter than sucrose and about 110 times sweeter than aspartame.
E 969  can be blended with many other natural and artificial sweeteners.

In 2013, it was approved for use in foods within EU with the E number E969.
In 2014, FDA approved E 969  as a non-nutritive sweetener and flavor enhancer within United States in foods generally, except meat and poultry.

Safety of E 969 
The FDA acceptable daily intake of advantame for humans is 32.8 mg per kg of bodyweight (mg/kg bw), while according to EFSA it is 5 mg per kg of bodyweight (mg/kg bw).
Estimated possible daily intakes from foods are well below these levels.
NOAEL for humans is 500 mg/kg bw in EU. 
Ingested advantame can form phenylalanine, but normal use of E 969  is not significant to those with phenylketonuria. 
E 969  also has no adverse effects in type 2 diabetics. 
E 969  is not considered to be carcinogenic or mutagenic.
The Center for Science in the Public Interest ranks advantame as safe and as generally recognized as safe.

Sweetness of E 969 
Relative sweetness of E 969  varies. 
E 969  depends on the concentration and food/matrix in which it is used. 
In water solutions of E 969 , that are equivalently sweet to water solutions of 3–14 percentage sucrose by weight (wt%), E 969  is 7000–47700 times sweeter. 
Relative sweetness of E 969  increases logarithmically as the sucrose concentration of a comparably sweet sucrose solution increases, but eventually reaches a plateau. 
By extrapolation, sweetness of an E 969  water solution is estimated to reach a maximum at a concentration that is equivalent to a 15.8 wt% sucrose water solution.

Chemistry of E 969 
E 969  is formally a secondary amine of aspartame and 3-(3-hydroxy-4-methoxyphenyl)propanal (HMPA). 
Structurally E 969  resembles a combination of aspartame and phyllodulcin.
E 969  has 2 stereocenters and 4 stereoisomers.

E 969  can be made from aspartame and vanillin.
Vanillin is transformed to HMPA in 4 steps.
3-hydroxy-4-methoxycinnamaldehyde (HMCA) is formed in the third step. 
HMCA is hydrogenated to HMPA in the final step. 
HMPA is selectively hydrogenated with palladium on aluminium oxide and platinum on carbon in one step to advantame in methanol with aspartame. 
Product is crystallized. 
Crude crystals are washed, recrystallized, washed and dried.

At 15 °C the solubility of E 969  is 0.76 g/L in water, 7.98 g/L in ethanol and 1.65 g/L in ethyl acetate. 
At 25 °C the solubilities are 0.99 g/L, 13.58 g/L and 2.79 g/L, respectively. 
At 40 °C the solubilities are 2.10 g/L, 38.27 g/L and 7.96 g/L, respectively. 
At 50 °C the solubilities are 3.10 g/L, 98.68 g/L and 16.00 g/L, respectively.

E 969  as a dry powder degrades very slowly at 25 °C and 60% relative humidity and can last for years under such conditions. 
E 969  can last for more than a year in aqueous solutions at pH 3.2. 
This corresponds to the typical pH of soft drinks. 
E 969  degrades faster at higher temperatures and humidity, but is generally more stable than aspartame. 
Unlike aspartame, E 969  doesn't form a diketopiperazine via intra-molecular cyclization due to steric hindrance by the vanillyl group.

Metabolism of E 969 
In humans, 89% of the ingested E 969  is excreted in feces and 6.2% in urine. 
Some is excreted unchanged, but most as metabolites. 
E 969  is poorly absorbed, rapidly metabolized and only small amounts of it and its metabolites can be detected in blood shortly after ingestion.

52% of the ingested dose is excreted in feces as de-esterified E 969  and 30% as N-(3-(3-hydroxy-4-methoxyphenyl))propyl-L-aspartic acid and as an equivalent molar amount of phenylalanine. 1% of the ingested dose is excreted in urine as the aforementioned aspartic acid analog, 1.9% as 5-(3-aminopropyl)-2-methoxyphenyl and 2.3% as de-esterified E 969 . 
Methanol forms in de-esterification, but this is considered insignificant at E 969  concentrations intended to be used in foods, and in comparison to methanol naturally formed in body and to methanol naturally found in foods.

History of E 969 
Ajinomoto developed E 969  and announced its structure publicly in print in 2008. 
At first E 969  was identified by the laboratory code ANS9801. 
Aspartame, neotame and aspartame N-substituted with asparagine via amide bond (covered in US patent 5,286,509) were selected as the lead compounds for research that lead to E 969 .

Benefits of E 969 
-Enables ease of formulation
-Enables water dilution
--Superior conditioning
-Imparts slip on wet hair
-Enables resistance to breakage
-Enables improved alignment
-Enables style retention
-To the best of our knowledge this product complies with California Prop 65

Uses of E 969 
-Amino silicone emulsion providing superior conditioning benefits
-Rinse-off Conditioner
-Leave-in Conditioner
-Shampoo
-Hair Colorant
-Hair Perm
-Styling Product

E 969  is a new ultrahigh potency sweetener and flavor enhancer developed by Ajinomoto. 
E 969  is derived from aspartame and vanillin. 
E 969  is approximately 20,000 times sweeter than sugar and 100 times sweeter than aspartame. 
E 969  has zero calories and a clean, sweet, sugar-like taste with no undesirable taste characteristics. 
Suitable for most low- and non-calorie product formulations, E 969  can be used in cooking and baking. 
E 969  gives food and drink manufacturers a new sweetening alternative to meet consumer demand for more low-calorie foods and beverages.

E 969 is a new high-intensity sweetener that the FDA has deemed safe to be used as a tabletop sweetener and a flavor enhancer in food (except for meat and poultry). 
E 969’s made by Ajinomoto, a manufacturer of food additives, including MSG. 
Interestingly, E 969 has also been approved as an artificial flavor. 
E 969 is a water-soluble, crystalline white powder made from aspartame and vanillin, which is basically an artificial version of vanilla extract.

Substance identity

CAS no.: 714229-20-6
Mol. formula: C24H30N2O7

Hazard classification & labelling of E 969 
According to the notifications provided by companies to ECHA in REACH registrations no hazards have been classified.

About E 969 
E 969  is registered under the REACH Regulation and is manufactured in and / or imported to the European Economic Area, but the tonnage data is confidential.

Consumer Uses of E 969
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 E 969 is most likely to be released to the environment.

Article service life of E 969
ECHA has no public registered data on the routes by which E 969 is most likely to be released to the environment. 
ECHA has no public registered data indicating whether or into which articles the substance might have been processed.

Widespread uses by professional workers of E 969
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 types of manufacture using E 969. 
ECHA has no public registered data on the routes by which E 969 is most likely to be released to the environment.

Formulation or re-packing of E 969
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 E 969 is most likely to be released to the environment.

Uses at industrial sites of E 969
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 types of manufacture using E 969. 
ECHA has no public registered data on the routes by which E 969 is most likely to be released to the environment.

Manufacture of E 969
ECHA has no public registered data on the routes by which E 969 is most likely to be released to the environment.

Synonyms:
Advantame anhydrous
Advantame
245650-17-3
M501L2WP44
L-Phenylalanine, N-[3-(3-hydroxy-4-Methoxyphenyl)propyl]-L-a-aspartyl-, 2-Methyl ester
(S)-3-((3-(3-hydroxy-4-methoxyphenyl)propyl)amino)-4-(((S)-1-methoxy-1-oxo-3-phenylpropan-2-yl)amino)-4-oxobutanoic acid
UNII-M501L2WP44
SCHEMBL145845
DTXSID60179302
ANS-9801
L-Phenylalanine, N-(3-(3-hydroxy-4-methoxyphenyl)propyl)-l-alpha-aspartyl-, 2-methyl ester
Q16886625
Phenylalanine, N-(3-(3-hydroxy-4-methoxyphenyl)propyl)-alpha-aspartyl-, 2-methyl ester
(3S)-3-[3-(3-hydroxy-4-methoxyphenyl)propylamino]-4-[[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino]-4-oxobutanoic acid
L-PHENYLALANINE, N-(3-(3-HYDROXY-4-METHOXYPHENYL)PROPYL)-L-.ALPHA.-ASPARTYL-, 2-METHYL ESTER
PHENYLALANINE, N-(3-(3-HYDROXY-4-METHOXYPHENYL)PROPYL)-.ALPHA.-ASPARTYL-, 2-METHYL ESTER
Advantame monohydrate
3ZA6810AWX
714229-20-6 [RN]
Advantame [Wiki]
L-Phenylalanine, N-[3-(3-hydroxy-4-methoxyphenyl)propyl]-L-α-aspartyl-, methyl ester, hydrate (1:1) [ACD/Index Name]
Methyl N-[3-(3-hydroxy-4-methoxyphenyl)propyl]-L-α-aspartyl-L-phenylalaninate hydrate (1:1) [ACD/IUPAC Name]
Methyl-N-[3-(3-hydroxy-4-methoxyphenyl)propyl]-L-α-asparagyl-L-phenylalaninathydrat (1:1) [German] [ACD/IUPAC Name]
N-[3-(3-Hydroxy-4-méthoxyphényl)propyl]-L-α-aspartyl-L-phénylalaninate de méthyle, hydrate (1:1) [French] [ACD/IUPAC Name]
UNII-3ZA6810AWX
MFCD28144745
UNII:3ZA6810AWX