Advantame

Last updated
Advantame
Advantame Structural Formula V.1.svg
Names
IUPAC name
Methyl N-[3-(3-Hydroxy-4-methoxyphenyl)propyl]aspartylphenylalaninate
Systematic 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
Identifiers
3D model (JSmol)
ChemSpider
E number E969 (glazing agents, ...)
PubChem CID
UNII
  • InChI=1S/C24H30N2O7/c1-32-21-11-10-17(14-20(21)27)9-6-12-25-18(15-22(28)29)23(30)26-19(24(31)33-2)13-16-7-4-3-5-8-16/h3-5,7-8,10-11,14,18-19,25,27H,6,9,12-13,15H2,1-2H3,(H,26,30)(H,28,29)/t18-,19-/m0/s1
    Key: YTKBWWKAVMSYHE-OALUTQOASA-N
  • InChI=1/C24H30N2O7/c1-32-21-11-10-17(14-20(21)27)9-6-12-25-18(15-22(28)29)23(30)26-19(24(31)33-2)13-16-7-4-3-5-8-16/h3-5,7-8,10-11,14,18-19,25,27H,6,9,12-13,15H2,1-2H3,(H,26,30)(H,28,29)/t18-,19-/m0/s1
    Key: YTKBWWKAVMSYHE-OALUTQOABU
  • COC1=C(C=C(C=C1)CCCN[C@@H](CC(=O)O)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)OC)O
Properties
C24H30N2O7
Molar mass 458.511 g·mol−1
Appearancewhite to yellow powder [1]
Melting point 101.5 °C (214.7 °F; 374.6 K) [1]
0.99 g/L at 25 °C [2]
Hazards
Safety data sheet (SDS) External MSDS
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Advantame is a non-caloric artificial sweetener and aspartame analog by Ajinomoto. [2] By mass, it is about 20,000 times sweeter than sucrose and about 110 times sweeter than aspartame. [3] It has no notable off-flavors when compared to sucrose and tastes sweet a bit longer than aspartame and is chemically more stable. It can be blended with many other natural and artificial sweeteners. [2]

Contents

Advantame can be used as a table top sweetener and in certain bubblegums, flavored drinks, milk products, jams and confectionery among other things. [4]

In 2013, it was approved for use in foods within EU with the E number E969. [4] In 2014, FDA approved advantame as a non-nutritive sweetener and flavor enhancer within United States in foods generally, except meat and poultry. [5]

Safety

The FDA acceptable daily intake of advantame for humans is 32.8 mg per kg of bodyweight (mg/kg bw), [6] while according to EFSA it is 5 mg per kg of bodyweight (mg/kg bw). [1] Estimated possible daily intakes from foods are well below these levels.[ quantify ] NOAEL for humans is 500 mg/kg bw in EU. Ingested advantame can form phenylalanine, but normal use of advantame is not significant to those with phenylketonuria. It also has no adverse effects in type 2 diabetics. It is not considered to be carcinogenic or mutagenic. [1]

The Center for Science in the Public Interest ranks advantame as safe [7] and as generally recognized as safe. [8]

Sweetness

Relative sweetness of advantame varies. It depends on the concentration and food/matrix in which it is used. In water solutions of advantame, that are equivalently sweet to water solutions of 3–14 percentage sucrose by weight (wt%), advantame is 7000–47700 times sweeter. Relative sweetness of advantame increases logarithmically as the sucrose concentration of a comparably sweet sucrose solution increases, but eventually reaches a plateau. By extrapolation, sweetness of an advantame water solution is estimated to reach a maximum at a concentration that is equivalent to a 15.8 wt% sucrose water solution. [2]

Chemistry

Advantame is formally a secondary amine of aspartame and 3-(3-hydroxy-4-methoxyphenyl)propanal (HMPA). Structurally advantame resembles a combination of aspartame and phyllodulcin. [2]

Advantame has 2 stereocenters and 4 stereoisomers.

Advantame can be made from aspartame and vanillin. [2] Vanillin is transformed to HMPA in 4 steps. [9] 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. [1]

At 15 °C the solubility of advantame 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. [2]

Advantame as a dry powder degrades very slowly at 25 °C and 60% relative humidity and can last for years under such conditions. It can last for more than a year in aqueous solutions at pH 3.2. This corresponds to the typical pH of soft drinks. It degrades faster at higher temperatures and humidity, but is generally more stable than aspartame. Unlike aspartame, advantame doesn't form a diketopiperazine via intra-molecular cyclization due to steric hindrance by the vanillyl group. [2]

Metabolism

In humans, 89% of the ingested advantame is excreted in feces and 6.2% in urine. Some is excreted unchanged, but most as metabolites. Advantame is poorly absorbed, rapidly metabolized and only small amounts of it and its metabolites can be detected in blood shortly after ingestion. [1]

52% of the ingested dose is excreted in feces as de-esterified advantame 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 advantame. Methanol forms in de-esterification, but this is considered insignificant at advantame concentrations intended to be used in foods, and in comparison to methanol naturally formed in body and to methanol naturally found in foods. [1]

History

Ajinomoto developed advantame and announced its structure publicly in print in 2008. At first advantame 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 advantame. [9]

Notes

  1. 1 2 3 4 5 6 7 "Scientific Opinion on the safety of advantame for the proposed uses as a food additive". EFSA Journal. 11 (7). 2013. doi: 10.2903/j.efsa.2013.3301 . ISSN   1831-4732.
  2. 1 2 3 4 5 6 7 8 Nabors 2012, p. 31–44
  3. Nabors 2012, p. 2–3
  4. 1 2 "EUR-Lex - 32014R0497 - EN - EUR-Lex". eur-lex.europa.eu. Retrieved 2019-09-14.
  5. "Food Additives Permitted for Direct Addition to Food for Human Consumption; Advantame". Federal Register. 2014-05-21. Archived from the original on 2017-06-03. Retrieved 2019-09-14.
  6. "Additional Information about High-Intensity Sweeteners Permitted for Use in Food in the United States". FDA. 2019-02-09.
  7. "Chemical Cuisine | Center for Science in the Public Interest". cspinet.org. Retrieved 2019-09-14.
  8. 25. GRAS flavoring substances. S2CID   100599854.
  9. 1 2 Weerasinghe DK, et al. (2008). Sweetness and sweeteners: biology, chemistry, and psychophysics. American Chemical Society. pp. 463–478. ISBN   9780841274327. OCLC   173368780.

Related Research Articles

<span class="mw-page-title-main">Aspartame</span> Artificial non-saccharide sweetener

Aspartame is an artificial non-saccharide sweetener 200 times sweeter than sucrose and is commonly used as a sugar substitute in foods and beverages. It is a methyl ester of the aspartic acid/phenylalanine dipeptide with brand names NutraSweet, Equal, and Canderel. Aspartame was approved by the US Food and Drug Administration (FDA) in 1974, and then again in 1981, after approval was revoked in 1980.

<span class="mw-page-title-main">Stevia</span> Sweetener and sugar substitute

Stevia is a sweet sugar substitute extracted from the leaves of the plant species Stevia rebaudiana native to Paraguay and Brazil.

<span class="mw-page-title-main">Sucralose</span> Chemical compound

Sucralose is an artificial sweetener and sugar substitute. The majority of ingested sucralose is not broken down by the body, so it is noncaloric. In the European Union, it is also known under the E number E955. It is produced by chlorination of sucrose, selectively replacing three of the hydroxy groups—in the C1 and C6 positions of fructose and the C4 position of glucose—to give a 1,6-dichloro-1,6-dideoxyfructose–4-chloro-4-deoxygalactose disaccharide. Sucralose is about 320 to 1,000 times sweeter than sucrose, three times as sweet as both aspartame and acesulfame potassium, and twice as sweet as sodium saccharin.

<span class="mw-page-title-main">Fructose</span> Simple ketonic monosaccharide found in many plants

Fructose, or fruit sugar, is a ketonic simple sugar found in many plants, where it is often bonded to glucose to form the disaccharide sucrose. It is one of the three dietary monosaccharides, along with glucose and galactose, that are absorbed by the gut directly into the blood of the portal vein during digestion. The liver then converts both fructose and galactose into glucose, so that dissolved glucose, known as blood sugar, is the only monosaccharide present in circulating blood.

<span class="mw-page-title-main">Sugar substitute</span> Sugarless food additive intended to provide a sweet taste

A sugar substitute is a food additive that provides a sweetness like that of sugar while containing significantly less food energy than sugar-based sweeteners, making it a zero-calorie or low-calorie sweetener. Artificial sweeteners may be derived through manufacturing of plant extracts or processed by chemical synthesis. Sugar substitute products are commercially available in various forms, such as small pills, powders, and packets.

<span class="mw-page-title-main">Xylitol</span> Synthetic sweetener

Xylitol is a chemical compound with the formula C
5
H
12
O
5
, or HO(CH2)(CHOH)3(CH2)OH; specifically, one particular stereoisomer with that structural formula. It is a colorless or white crystalline solid that is freely soluble in water. It can be classified as a polyalcohol and a sugar alcohol, specifically an alditol. The name derives from Ancient Greek: ξύλον, xyl[on] 'wood', with the suffix -itol used to denote sugar alcohols.

<span class="mw-page-title-main">Neohesperidin dihydrochalcone</span> Chemical compound

Neohesperidin dihydrochalcone, sometimes abbreviated to neohesperidin DC or simply NHDC, is an artificial sweetener derived from citrus.

<span class="mw-page-title-main">Saccharin</span> Chemical compound

Saccharin, also called saccharine or benzosulfimide, or used in saccharin sodium or saccharin calcium forms, is a non-nutritive artificial sweetener. Saccharin is a benzoic sulfimide that is about 500 times sweeter than sucrose, but has a bitter or metallic aftertaste, especially at high concentrations. It is used to sweeten products, such as drinks, candies, baked goods, tobacco products, excipients, and for masking the bitter taste of some medicines. It appears as white crystals and is odorless.

<span class="mw-page-title-main">Acesulfame potassium</span> Calorie-free sugar substitute

Acesulfame potassium, also known as acesulfame K or Ace K, is a synthetic calorie-free sugar substitute often marketed under the trade names Sunett and Sweet One. In the European Union, it is known under the E number E950. It was discovered accidentally in 1967 by German chemist Karl Clauss at Hoechst AG. In chemical structure, acesulfame potassium is the potassium salt of 6-methyl-1,2,3-oxathiazine-4(3H)-one 2,2-dioxide. It is a white crystalline powder with molecular formula C
4
H
4
KNO
4
S
and a molecular weight of 201.24 g/mol.

<span class="mw-page-title-main">Erythritol</span> Chemical compound

Erythritol (, ) is an organic compound, the naturally occurring achiral meso four-carbon sugar alcohol (or polyol). It is the reduced form of either D- or L-erythrose and one of the two reduced forms of erythrulose. It is used as a food additive and sugar substitute. It is synthesized from corn using enzymes and fermentation. Its formula is C
4
H
10
O
4
, or HO(CH2)(CHOH)2(CH2)OH.

<span class="mw-page-title-main">Neotame</span> Chemical compound

Neotame, also known by the trade name Newtame, is a non-caloric artificial sweetener and aspartame analog by NutraSweet. By mass, it is 8000 times sweeter than sucrose. It has no notable off-flavors when compared to sucrose. It enhances original food flavors. It can be used alone, but is often mixed with other sweeteners to increase their individual sweetness and decrease their off-flavors. It is chemically somewhat more stable than aspartame. Its use can be cost effective in comparison to other sweeteners as smaller amounts of neotame are needed.

<span class="mw-page-title-main">Astaxanthin</span> Chemical compound

Astaxanthin is a keto-carotenoid within a group of chemical compounds known as terpenes. Astaxanthin is a metabolite of zeaxanthin and canthaxanthin, containing both hydroxyl and ketone functional groups. It is a lipid-soluble pigment with red coloring properties, which result from the extended chain of conjugated double bonds at the center of the compound.

<span class="mw-page-title-main">Alitame</span> Chemical compound

Alitame is an aspartic acid-containing dipeptide sweetener. It was developed by Pfizer in the early 1980s and currently marketed in some countries under the brand name Aclame. Most dipeptides are not sweet, but the unexpected discovery of aspartame in 1965 led to a search for similar compounds that shared its sweetness. Alitame is one such second-generation dipeptide sweetener. Neotame, developed by the owners of the NutraSweet brand, is another.

<span class="mw-page-title-main">Sweetness</span> Basic taste

Sweetness is a basic taste most commonly perceived when eating foods rich in sugars. Sweet tastes are generally regarded as pleasurable. In addition to sugars like sucrose, many other chemical compounds are sweet, including aldehydes, ketones, and sugar alcohols. Some are sweet at very low concentrations, allowing their use as non-caloric sugar substitutes. Such non-sugar sweeteners include saccharin and aspartame. Other compounds, such as miraculin, may alter perception of sweetness itself.

<span class="mw-page-title-main">Brazzein</span> Protein

Brazzein is a protein found in the West African fruit Oubli. It was first isolated by the University of Wisconsin–Madison in 1994.

<span class="mw-page-title-main">Psicose</span> Chemical compound

D-Psicose (C6H12O6), also known as D-allulose, or simply allulose, is a low-calorie epimer of the monosaccharide sugar fructose, used by some major commercial food and beverage manufacturers as a low-calorie sweetener. First identified in wheat in the 1940s, allulose is naturally present in small quantities in certain foods.

<span class="mw-page-title-main">Isomaltulose</span> Chemical compound

Isomaltulose is a disaccharide carbohydrate composed of glucose and fructose. It is naturally present in honey and sugarcane extracts and is also produced industrially from table sugar (sucrose) and used as a sugar alternative.

The artificial sweetener aspartame has been the subject of several controversies since its initial approval by the U.S. Food and Drug Administration (FDA) in 1974. The FDA approval of aspartame was highly contested, beginning with suspicions of its involvement in brain cancer, alleging that the quality of the initial research supporting its safety was inadequate and flawed, and that conflicts of interest marred the 1981 approval of aspartame, previously evaluated by two FDA panels that concluded to keep the approval on hold before further investigation. In 1987, the U.S. Government Accountability Office concluded that the food additive approval process had been followed properly for aspartame. The irregularities fueled a conspiracy theory, which the "Nancy Markle" email hoax circulated, along with claims—counter to the weight of medical evidence—that numerous health conditions are caused by the consumption of aspartame in normal doses.

<span class="mw-page-title-main">Steviol glycoside</span> Sweet chemicals derived from the Stevia plant

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 of many sweeteners marketed under the generic name stevia and several trade names. They also occur in the related species S. phlebophylla and in the plant Rubus chingii (Rosaceae).

Magnesium aspartate, the chelated magnesium salt of aspartic acid, it is a mineral supplement.

References