Quick Search

PRODUCTS

E 961

E 961, also known by the trade name Newtame, is a non-caloric artificial sweetener and aspartame analog by NutraSweet.
By mass, E 961 is 8000 times sweeter than sucrose.
E 961 has no notable off-flavors when compared to sucrose. 

CAS:    165450-17-9
MF:    C20H30N2O5
MW:    378.46
EINECS:    605-408-8

E 961 enhances original food flavors. 
E 961 can be used alone, but is often mixed with other sweeteners to increase their individual sweetness (i.e. synergistic effect) and decrease their off-flavors (e.g. saccharin). 
E 961 is chemically somewhat more stable than aspartame. 
E 961's use can be cost effective in comparison to other sweeteners as smaller amounts of neotame are needed.

E 961 is suitable for use in carbonated soft drinks, yogurts, cakes, drink powders, and bubble gums among other foods. 
E 961 can be used as a table top sweetener for hot drinks like coffee. 
E 961 covers bitter tastes.

In 2002, FDA approved E 961 as a non-nutritive sweetener and flavor enhancer within United States in foods generally, except meat and poultry.
In 2010, it was approved for use in foods within EU with the E number E961.
E 961 has also been approved as an additive in many other countries outside US and EU.

E 961's metabolism is fast and is not retained in the body. 
Methanol forms in its metabolism. 
Only trace amounts of E 961 is added to foods, so the amount of methanol is insignificant for health. 
E 961 is safe for type 2 diabetics and those with phenylketonuria.

French scientists Claude Nofre and Jean-Marie Tinti invented E 961.
In 1992 they filed a patent for neotame within US, which was granted in 1996.

In US and EU, the acceptable daily intake (ADI) of neotame for humans is 0.3 and 2 mg per kg of bodyweight (mg/kg bw), respectively. 
NOAEL for humans is 200 mg/kg bw per day within EU.
Estimated possible daily intakes from foods are well below ADI-levels. 
Ingested neotame can form phenylalanine, but in normal use of neotame, E 961 is not significant to those with phenylketonuria. 
E 961 also has no adverse effects in type 2 diabetics.

E 961 is not considered to be carcinogenic or mutagenic.
The Center for Science in the Public Interest ranks E 961 as safe.
E 961 is sweet because it binds to TAS1R2-receptors of mouth as an agonist. 
Aspartame binds to the same receptor.

Water solutions of neotame, that are equivalent in sweetness to sucrose water solutions, increase logarithmically in relative sweetness as the sucrose concentration of a comparably sweet sucrose solution increases, until a plateau is reached. 
Maximum sweetness is reached at E 961 solution concentrations that are relatively as sweet as a water solution that is 15.1 percentage sucrose by weight, i.e. at 15.1 sucrose equivalence % (SE%). 
For comparison, acesulfame K, cyclamate and saccharin reach their maximum sweetness at 11.6 SE%, 11.3 SE% and 9 SE%, respectively.

E 961 is a high-potency sweetener, and it is 6,000 to 10,000 times sweeter than sugar (sucrose), and even around 30 to 60 times sweeter than aspartame. 
E 961 contains flavor-enhancing properties and compared to sucrose or aspartame it has a relatively lower cost per sweetness factor.

Synthesis
E 961 is synthesized from aspartame through a reductive alkylation with 3,3-dimethyl-butylaldehyde in a palladium catalyst with methanol.
The stereochemistry of aspartame is conserved during the synthesis and therefore, E 961 and aspartame have the same stereochemistry. 
(2S),(3S)-stereoisomer of E 961 is needed to synthesize the (2S),(3S)-stereoisomer of neotame.

E 961 is the world's most sweet sweetener by far, is also the world's most safe sweetener tastes closest to sucrose.
E 961 pure sweet, is very close to aspartame, no other strong sweet agent, often with the bitterness and metallic taste. 
Under a variety of conditions, E 961's flavor distribution are no significant difference from aspartame , while the neotame sweet stimulate the formation and sucrose is similar, but compared with aspartame, can feel the sweetness of the initial lag slightly, and the sweet taste of duration, slightly long. 
Similar with aspartame, in complex food system, E 961 is according to need to be other ingredients, such as polyol, sucrose or containing oxygen acid to change these temporary effect.

In October 2003, China's Ministry of Health approved neotame as a sweetener common in a variety of foods and beverages, add the amount according to the requirement of production, E 961 is China's Ministry of health only approved in food, is not limited to use of a safe sweetener. 
A large number of the results show that , E 961 is practical to include children, pregnant women, lactating women and patients with diabetes mellitus, all populations. 
The usage of neotame without of phenylketonuric patients indicates especially, E 961 is the sweetener market only without taboo groups of artificial sweet taste agent.
E 961 in the human body can be quickly metabolism. 
The main metabolic pathway is through the body to produce the enzyme in the hydrolysis of methyl ester, the last generation of the defatted neotame and methanol. 
E 961 in human generated by decomposition of methanol is far not enough to pose a health hazard to the human body. 

Compared with ordinary food such as fruit, vegetables and vegetable juice, decomposed from E 961 is minimal. 
For example, tomato juice in methanol content exceeded containing neotame beverages 200 times. 
E 961 can with urine and feces completely eliminated from the body, not in the human body accumulation.
E 961 can also enhance the flavor of certain foods and beverages, especially acid type fruit flavor (such as orange, lemon and grapes) and cherry flavor. 
And aspartame is different, E 961 and acesulfame, saccharin has no synergistic effect between sweetness, providing more convenience for the new product development of food and beverage manufacturers, because neotame can be used alone, or with other nutritional or non nutritive sweeteners mixed use. 

E 961's appearance provides a more flexible solution for sweet food manufacturers. 
Adding can inhibit the aging of starch in starch food, prolong the shelf life of food products; in the egg, adding inhibited protein denaturation , keep good taste in fish protein rich food such as food.

E 961 Chemical Properties
Melting point: 83-85°C
Alpha: D -54.84° (c = 1 in methanol); D20 -39.8° (c = 0.5 in water)
Boiling point: 565.3±50.0 °C(Predicted)
Density: 1.133±0.06 g/cm3(Predicted)
Storage temp.: Keep in dark place,Sealed in dry,2-8°C
Solubility: Chloroform (Sparingly), Ethanol (Sparingly), Ethyl Acetate (Sparingly), Methanol
pka: pKa1 3.01; pKa2 8.02(at 25℃)
Form: neat
Color: White to Off-White
Optical activity: [α]/D -41.0±3.0°, c = 0.5 in H2O
BRN: 8352678
Stability: Hygroscopic
InChIKey: HLIAVLHNDJUHFG-HOTGVXAUSA-N

E 961 has similar stability as aspartame, but has greater stability especially in heated and dairy foods. 
Increased temperature, moisture or pH increase losses, and are the main relevant properties of a food when considering the stability of E 961. 
For example, about 90% of original E 961 remains after 8 weeks of storage in pH 3.2 beverages. 
E 961 is especially stable as a dry powder at room temperature and humidity even if mixed with e.g. glucose or maltodextrin, and is relatively inert in foods with reducing sugars like fructose.

Unlike aspartame, E 961 doesn't form diketopiperazines via intra-molecular cyclization due to its N-alkyl substitution with 3,3-dimethylbutyl. 
This increases E 961's heat stability.

Over 1000 g of neotame dissolves in 1 kg of ethanol at 15 °C. 
At 15 °C the solubility of E 961 is 10.6 g/kg in water and 43.6 g/kg in ethyl acetate. 
At 25 °C the solubilities are 12.6 g/kg and 77.0 g/kg, respectively. 
At 40 °C the solubilities are 18.0 g/kg and 238 g/kg, respectively. 
At 50 °C the solubilities are 25.2 g/kg and 872 g/kg, respectively.
E 961 is acidic and its 0.5 wt% solution has a pH of 5.80.

E 961 occurs as an odorless, white to off-white powder. 
E 961 has an intense sweet taste 7000–13 000 times sweeter than sucrose depending on the matrix.
E 961 is odorless and has an intense, sweet taste. 
E 961 is 7,000 to 13,000 times sweeter than sucrose, depending on the food matrix. 
Normal metabolic processes convert E 961 to de-esterified neotame and methanol. 
Based on E 961's metabolism and extremely low use levels, neotame provides no calories. 
The stability of E 961 is affected by moisture, pH and temperature.

Uses    
An alkylated dipeptide reported to be 6000 to 10000 times sweeter than sucrose; structurally related to Aspartame. 
A non-nutritive sweetener.
E 961 is a high intensity sweetener and flavor enhancer for use in foods, except in meat and poultry. 
E 961 is 7,000–13,000 times sweeter than sugar and has a clean, sweet taste. 
E 961 is a derivative of the dipep- tide composed of amino acids, aspartic acid, and phenylalanine. 
E 961 can be blended with nutritive sweeteners such as sucrose and high fructose corn syrup as well as with high intensity sweeteners such as aspartame and sucralose. 
E 961 uses include beverages, baked goods, desserts, cereals. 
E 961 functions as a flavor enhancer in certain applica- tions and flavor systems, such as mint-flavored chewing gum.

E 961 is a water-soluble, nonnutritive, intense sweetening agent used in beverages and foods. 
E 961 is structurally related to aspartame and is about 7000–13 000 times sweeter than sucrose, and about 30–60 times sweeter than aspartame, making it the sweetest artificial sweetener available. 
E 961 is said to have a ‘clean’ sweet taste in contrast to the bitter, metallic aftertaste associated with saccharin. 
Although E 961 has approximately the same caloric value as sucrose (1.2 kJ/g) the small quantities used to achieve a desired level of sweetness in a formulation mean that it is essentially nonnutritive.
E 961 may be used in sub-sweetening quantities as a flavor enhancer, e.g. with mint or strawberry flavor.

Manufacture
Industrially E 961 is made from 3,3-dimethylbutanal and aspartame via reductive amination.
They are dissolved in methanol, palladium on carbon catalyst is added, air is replaced with hydrogen and the reaction is carried out in room temperature under pressure for a few hours. Catalyst is filtered out. 
E 961 can be aided with diatomaceous earth. 
E 961 is distilled followed by addition of water. 
The mixture is cooled for a few hours, E 961 is isolated via centrifugation, washed with water and vacuum dried. 
E 961 is milled to suitable size.

Metabolism
In humans and many other animals like dogs, rats and rabbits, E 961 is rapidly, but incompletely absorbed. 
E 961's metabolites are not retained or concentrated in specific tissues.

In humans at oral doses of about 0.25 mg per kg of bodyweight (mg/kg bw), about 34% is absorbed into blood. 
Pharmacokinetics of oral doses of 0.1–0.5 mg/kg bw are somewhat linear, and at such doses, maximum E 961 concentration in blood plasma is reached after about 0.5 hours with a half-life of about 0.75 hours. 
In blood and in body in general, non-specific esterases degrade E 961 to de-esterified neotame and methanol, which is the main metabolic pathway in humans. 
E 961 has a plasma half-life of about 2 hours, and is the main metabolite in plasma.

In humans, over 80% of the original oral dose is excreted in feces and urine within 48 hours and the rest later. 
About 64% of the original dose is excreted in feces mostly as metabolites. 
Major metabolite in feces is the de-esterified E 961. 
Over 1% of the original dose is excreted in feces as N-(3,3-dimethylbutyl)-L-aspartyl - L - phenylalanine. 
Over 1% is excreted in urine as carnitine conjugate of 3,3-dimethylbutyric acid. 
Other minor metabolites form.

The major metabolic pathway leads to N-(3,3-dimethylbutyl)-L-aspartyl - L - phenylalanine with a side E 961 of methanol, and the minor pathway happens when the N-(3,3-dimethylbutyl)-L-aspartyl - L - phenylalanine is oxidized into 3,3-dimethylbutyric acid. 
The side products for the minor pathway is methanol, aspartic acid and phenylalanine.
E 961 from neotame metabolism is insignificant at regulated levels used in foods and in comparison to methanol naturally found in foods.

Synthesis
E 961's sweetness is very high, usually it is 50 times higher than that of sucrose. 
According to different sources, there is a natural extract, natural product chemistry modified semisynthetic products and pure chemical synthesis products. 
A large supply of natural extracts is the main Stevia extract and long winded Sweet and natural product chemistry modified products such as aspartame, neotame and sucralose, pure synthetic chemical products such as saccharin, cyclamate and acesulfame.
E 961 can be used for low calorie baked food sweetener, but must have a good thermal stability. 

E 961 has been approved for use in food, but due to its poor thermal stability and is not suitable for baking food. 
American newt company newest development of E 961 is aspartame derivative, its thermal stability and sweetness have greatly improved and sweet pure than aspartame, sweet good distribution is used for baking food, which has great potential for development of the sweetener.
E 961 is aspartate dipeptide derivatives, is a new product developed at a cost of $80 million by American newt company after aspartame, representing the latest achievements of sweetener research field. 
E 961 is according to the human sweet receptor double hydrophobic binding hypothesis. 
In E 961 molecule with a hydrophobic groups and the formation of aspartame derivatives. It can also act on the human sweet receptor of two hydrophobic binding sites and therefore sweetness increased greatly, 6000 to 10000 times sweeter than sucrose, 30 to 60 times than Biasiba sweet.

E 961 retains many excellent characteristics such as aspartame, pure sweet taste and good flavor enhancing properties distribution, no energy, no caries, stable in acidic medium. Moreover, E 961 is still a lot better than aspartame in dry conditions, it has a longer shelf life; in neutral medium or instantaneous high temperature sterilization conditions, E 961's stability greatly exceed aspartame, which can be used as a sweetener in baking. 
E 961 can also be used together with reducing sugar and aldehyde flavor without adverse reaction, E 961's safety is better than aspartame and has been greatly improved. 
Due to E 961's high sweetness, etc. 
Sweeter is lower than the cost of aspartame. 
Therefore, E 961 has huge market potential. 
In December of 1998, E 961 as food sweeteners status of application have been proposed in the United States, and some other countries for the certification work is in July 9, 2002 . The U. S. Food and Drug Administration (FDA) confirmed the E 961 safety and functional type, currently is in March 10, worldwide more regulatory agency and national review in 2003, China's Ministry of Health approval for neotame as a sweetener used in all kinds of food.

Solubility    
The solubility of E 961 in water, is 12.6g/L at 25℃, aspartame is 10g/L. 
Achieve multiple solubility with 10% of sucrose solution equal sweetness, namely MRS10% numerical, is about 740. 
That is, E 961 solubility ratio to reach 10% sucrose solution equal sweetness of solubility about 740 times. 
In contrast, the multiples of the E 961 is only about 19. 
E 961 is worth that neotame is as salt (such as phosphate) or complex (such as beta-the link dextrin compound), its dissolution rate in water will increase significantly. 
E 961 in anhydrous ethanol solubility is very high, at 25℃ about 950g/L, over aspartame (25℃for 3.7g/l) 250 times.

Safety and Toxicology    
E 961 enters the human body, about half of the two 3,3-methyl butyl aspartyl phenylalanine (DMB-Asp-Phe) form by the fecal excretion. 
The other half is wholly intact absorption, then further hydrolyzed into methanol and DMB-Asp-Phe. 
Most of the DMB-Asp-Phe (half2life 2H) through the urine, and there is no more in any organization other residues; only a small portion of the metabolism of the body, the formation of two 3,3-methyl butyric acid is by oxidation of 3,3-two methyl butyl part, as a kind of human carnitine esters (Carnitine ester, less than the new sweet intake of 5%) in the urine. 

E 961 is worth noting that aspartame metabolism is very different from the neotame. 
E 961 in the lumen of the gut or mucosal cell is decomposed into 3 components: aspartic acid (Asp), phenylalanine (Phe) and methanol. 
These components are absorbed into the body. 
Venous circulation is in amino acid metabolism. 
So E 961 can be concluded that, aspartame is metabolized completely absorbed, while more than 90% of neotame are excreted through the feces.

In the process of metabolism, E 961 can release 55% of phenylalanine. 
E 961 is one kind of 8 kinds of essential amino acids in the metabolic pathways of metabolism usually enter, but suffering from phenylketonuria (PKU) of the patients lack the ability to metabolize phenylalanine. 
Although compared with the meat, milk and other protein foods, E 961 content aspartame is very low. 
But many countries stipulate that foods containing aspartame must be indicated on the packaging of the E 961, which contains phenylalanine, PKU to remind the patient's attention. 

Because of the concentration to increase E 961's sweet food in neotame than aspartame low (low to 2.5%), so that the content of phenylalanine products is very low. 
Hydrate containing 17mg/L neotame single equivalent 7.08mg/L containing phenylalanine, E 961 was significantly lower than fruit juice. 
Moreover, 17mg in phenylalanine metabolic pathway by neotame Into the body of the effective number is lower, insufficient 0.7mg, release than aspartame low to about 0.25%. 
Therefore, E 961 increase sweet food. 
There is no need to specify which contains E 961.
From the extensive safety testing, E 961 can be seen, neotame and its main metabolic products DMB-Asp-Phe for normal body are safe and non mutagenic, teratogenic or carcinogenic, not on reproductive or target organ toxicity.
Very low usage, and the molecular and major metabolic product of very favorable pharmacokinetic properties make E 961 very high security.

Synonyms
Neotame
165450-17-9
(S)-3-((3,3-Dimethylbutyl)amino)-4-(((S)-1-methoxy-1-oxo-3-phenylpropan-2-yl)amino)-4-oxobutanoic acid
VJ597D52EX
NC 00723
HSDB 7965
NC-00723
(S)-3-((3,3-Dimethylbutyl)amino)-4-(((S)-1-methoxy-1-oxo-3-phenylpropan-2-yl)amino)-4-oxobutanoic ac
Neotame [NF]
L-Phenylalanine, N-(3,3-dimethylbutyl)-L-alpha-aspartyl-, 2-methyl ester
(3S)-3-(3,3-dimethylbutylamino)-4-[[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino]-4-oxobutanoic acid
N-(N-(3,3-dimethylbutyl)-L-alpha-aspartyl)-L-phenylalanine 1-methyl este
UNII-VJ597D52EX
MFCD09039056
NEOTAME [FHFI]
NEOTAME [INCI]
NEOTAME [FCC]
NEOTAME [II]
NEOTAME [MI]
NEOTAME [MART.]
NEOTAME [USP-RS]
MIRASEE 200
SCHEMBL4311
Neotame, analytical standard
NEOTAME (200 MG)
INS NO.961
CHEMBL3718532
CHEBI:83503
DTXSID50167950
INS-961
Neotame 1000 microg/mL in Water
methyl N-(3,3-dimethylbutyl)-L-alpha-aspartyl-L-phenylalaninate
s4442
ZINC33965935
AKOS016842430
AM84564
BCP9000982
CS-W011769
GS-3213
HY-W011053
(3S)-3-[(3,3-dimethylbutyl)amino]-3-{[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]carbamoyl}propanoic acid
BCP0726000005
E 961
E-961
N1112
450N179
A810640
Q415698
J-010204
N-[N-(3,3-dimethylbutyl)-L-alpha-aspartyl]-L-phenylalanine methyl ester
L-PHENYLALANINE, N-(N-(3,3-DIMETHYLBUTYL)-L-.ALPHA.-ASPARTYL)-1-METHYL ESTER
N-(N-(3,3-DIMETHYLBUTYL)-L-.ALPHA.-ASPARTYL)-L-PHENYLALANINE 1-METHYL ESTER
(3S)-4-[[(1S)-1-benzyl-2-methoxy-2-oxo-ethyl]amino]-3-(3,3-dimethylbutylamino)-4-oxo-butanoic acid
(S)-3-((3,3-Dimethylbutyl)amino)-4-(((S)-1-methoxy-1-oxo-3-phenylpropan-2-yl)amino)-4-oxobutanoicacid
 

  • Share !
E-NEWSLETTER