22839-47-0 Usage
Uses
Used in Food Industry:
Aspartame is used as a high-intensity sweetener for various food products, including cold breakfast cereals, desserts, topping mixes, and frozen desserts. It is often blended with other sweeteners to enhance taste and improve quality.
Used in Beverage Industry:
Aspartame is utilized as a low-calorie sweetener in a wide range of beverages, such as soft drinks, powdered drinks, and other non-alcoholic drinks. Its solubility in water and stability at room temperature make it suitable for these applications.
Used in Pharmaceutical Industry:
Aspartame is used in the preparation of low-sugar, low-calorie health food and pharmaceutical products for patients with diabetes, hypertension, obesity, and cardiovascular diseases. The dosage depends on the specific needs of the product.
Used as a Flavor Enhancer:
Aspartame is employed as a flavor enhancer in various food and beverage applications, improving the taste and overall consumer experience.
Used in Baking Industry:
Aspartame can be used in baked goods and baking mixes, but its usage should not exceed 0.5% by weight due to its instability at high baking temperatures.
Used in Cereal, Powdered Drinks, and Chewing Gum:
Aspartame is available in powder form and is used in limited quantities for cereals, powdered drinks, and chewing gum.
Used in Non-nutritive Sweeteners and Flavoring Agents:
Aspartame is classified as a non-nutritive sweetener and is used as a flavoring agent in various food and beverage products.
Packaging:
Aspartame is typically packed in 25 kg fiberboard drums, lined with plastic bags, for safe storage and transportation.
Artificial sweeteners
Aspartame is a kind of artificial sweeteners, belongs to the amino acid dipeptide derivatives, by the chemist developed ulcer drugs found in 1965. With low dosage, high sweetness (sweetness is 150 to 200 times of sucrose), good taste, enhance flavor of citrus and other fruits and reducing heat does not produce dental caries, toxicity than saccharin and other synthetic sweetening agent advantages, is widely applied to beverages, diabetic food and some slimming health food, our daily life to drink cola formula once containing the product.
Aspartame in the metabolic processes in the body and the main degradation products are phenylalanine, methanol and aspartic acid, does not enter blood circulation, and does not accumulate in the body, food for the health harmless. But due to metabolic defects in patients with phenylketonuria (PKU), excessive body phenylalanine can influence its development, so in patients with the disease to disable adding aspartame.
Neotame
Neotame 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. It is according to the human sweet receptor double hydrophobic binding hypothesis. In aspartame 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 .
It 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, it 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, its stability greatly exceed aspartame, which can be used as a sweetener in baking. Neotame can also be used together with reducing sugar and aldehyde flavor without adverse reaction, its safety is better than aspartame and has been greatly improved. Due to its high sweetness, etc. Sweeter is lower than the cost of aspartame. Therefore, neotame has huge market potential. In December of 1998, neotame 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 neotame 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.
The above information is edited by the lookchem Han Ya.
Content analysis
Accurately take sample of about 300 mg, moves into a 150ml beaker, dissolve in 96% formic acid 1.5ml, and glacial acetic 60ml. with crystal violet solution (ts-74), with 0.1 mol/L HClO4 immediately titrate to the end of green. At the same time a blank titration and make necessary correction. Each mI.0.1mol/L perchloric acid is the equivalent of 29.43mg C14H18N2O5.
Toxicity
Entering the human body can quickly metabolic day aspartic acid and phenylalanine, two kinds of amino acids are absorbed, which does not accumulate in the organization. But phenylketonuria patients cannot use. Therefore it is necessary to specially marked. Every year in China about 1500~2000 benzene acetone urine disease in children born, after eating can be in vivo abnormal accumulation caused by brain damage, mental development retardation and epilepsy.
The ADI value is 0~40mg/kg (FAO/WHO, 2001). Contains two ketone piperazine ADI value is 0~7.5.
GRAS (FDA, 172.804,2000).
Use limits
GB 2760-2001: all types of food (except canned food), are limited to GMP.
FAO/WHO (1984): sweets 0.3%, gum 1.0%; beverage 0.1%, 0.5% of breakfast cereals, and used for the preparation of diabetes, hypertension, obesity, cardiovascular patients with low sugar, low calorie health food, dosage depends on the need to set. Can also be used as flavor enhancer.
chemical property
White crystalline powder, odorless, there is strong sweet, sweet and pure, sweetness of sucrose was 100-200 times. Melting point is 235℃ (decomposition). Amino acids is with the general nature. In dry conditions or pH value of 2 to 5 range, it is stability, strong acidic water solution can hydrolyzed to produce amino acid monomer, in neutral or alkaline conditions it can be cyclized to diketopiperazine. Solubility in water (25℃) is relevant to pH value, pH 7.0 was 10.2%, pH value 3.72 is 18.2%. At 25, isoelectric point is pH value of 5.2. Mice by oral LD50 > 10 g/kg Adl is 0~40mg/kg (FAO/who, 1994)
Methods of production
1. By L-aspartate and L-phenylalanine methyl ester condensation.
2. By L-aspartic acid and L-phenylalanine methyl ester hydrochloride condensation.
There are two kinds of synthetic and enzymatic synthesis.
enzymic synthesis ：
Department of chemistry, Wuhan University, Tao Guoliang, gave the following synthetic route:
The preparation of I : 0.5mmol benzyloxy carbonyl aspartic acid, 1.5mmol phenylalanine methyl ester hydrochloride and 2.5ml water were added to 25 ml Erlenmeyer flask, with ammonia to adjust the pH to 6, adding 7mg of thermophilic protease, at 40℃mixing reaction for 6h. Filter and washed with distilled water, and drying to obtain white solid (I) 0.29g, 95.6% yield, melting point is 116 to 118 ℃. Elemental analysis results: C 62.96%, H6.09%.N of 6.65%.
preparation of II: it will be joined the conical flasks 0.5g sample I and 20mL3mol/L hydrochloride 25ml and 45℃ in the mixing reaction for 0.5h. Filtration and washing with distilled water, drying to obtain 0.32g the product II, yield is 92%, melting point is 129 to 131℃. Elemental analysis results: C 61.45%, H 5.42% , N 6.82%.
Preparation of III will 0.2g palladium carbon catalyst (10%), 20 ml of glacial acetic acid, 5 ml of water add 100 ml three necked flask, hydrogenation activation 1.5h. Join 0.6g II 20 ml acetic acid dissolution and, at 30℃ stirring hydrogenated after 6h. the reaction is completed after filtration, catalyst with acetic acid washing 3 times; the filtrate and washings were concentrated under reduced pressure to dry, 15ml of benzene, continue to decompress and concentrate to dry white solid, and drying to obtain 0.38g the product III, and the yield was 92.3%, the melting point is 245 ℃. The elemental analysis results: C 55.63%, H6.23%, N 8.96%.
Chemical synthesis method
The aspartic acid and phenylalanine as raw material, by amino protection, anhydride, condensation, hydrolysis, neutralization and other steps of the synthesis. Different protecting groups, different methylated sequence can have a variety of different synthesis methods. Such as the use of formyl as protecting groups and after methyl esterification process route.Into a 250ml flask into 27mL 95% of the methanol and 0.2g oxidation of magnesium and magnesium oxide is dissolved, add 100ml 98% of acetic anhydride, at this time, the temperature gradually rose to 40 ℃, adding acid 67gL-aspartic, heated to 50℃, stirring reaction time 2.5h insulation and fill with 15mL98% acetic anhydride, temperature and reaction time 2.5h, join 16ml isopropanol and continue for 1.5h, the reaction after cooling to room temperature.
Put the inner anhydride materialized to join 1000ml flask, add 207mL ethyl acetate and 66Gl-phenylalanine, stirring 1.5h in 25 to 30℃, add the glacial acetic acid 126mL, continue to reflect 4.5h, the reaction after the end of the vacuum to remove the solvent and to the temperature of the reaction system 65℃ so far. Then add 35% hydrochloric acid methylmercury, heating to 60 ℃, return at the end of the reaction of the hydrolysis of 2h, atmospheric distillation until boiling temperature of 63℃ (reaction temperature of 73 degrees C) so far, adding methanol 180, to continue the distillation to the system temperature of 85 ℃ so far. After cooled to 25℃, the removal of the vacuum light group.
Adding 35% hydrochloric acid 54mL to the hydrolysis liquid, methanol 9mL and water 43mL. In 20 to 30℃for esterification reaction was then filtered, washed separation from α-APM hydrochloride. It dissolves in 600ml distilled water, to 40 to 50 ℃ of 5%~10% NaOH solution and to Ph=4.5. cooling below, filtering, washing to α-APM crude product, and then dissolved in 500 ml of methanol and water (volume ratio of 1:2) mixture. The cooling crystallization, filtration washing, vacuum drying 45% yield in terms of L-phenylalanine.
The Japanese scholars put forward a route without protection:
90g phenylalanine methyl ester hydrochloride is dissolved in 450mL water, 24g sodium carbonate neutralization, two vinyl chloride extraction and 2350mL obtained. Adding 9g phenylalanine methyl ester of acetic acid and methanol extracts 8mL, 15.2g aspartic anhydride hydrochloride added at-20 deg.c, stirring for 30min, hot water and sodium carbonate were added to 70~80 350mL C (5.7g) 300mL. solution with 150mL two vinyl chloride 2 remaining after extraction of phenylalanine methyl ester, water with dilute hydrochloric acid to adjust the Ph value to the 4.8. of the aqueous solution of paper electrophoresis measured with 18.2G (molar yield of 60%) and 6.1g (α-APM beta 20% molar yield) β--APM. This solution is vacuum concentration 100mL, plus.36% hydrochloric acid 30mL, set the refrigerator overnight. A-APM-HCl 21.3g Precipitation Crystallization (yield 58%), the crystallization of filtered and dissolved in 200mL water solution. Stirring at 50 ℃, with 5% sodium carbonate solution to adjust the Ph value to 4.8, and then place the refrigerator overnight in the analysis And filtering to obtain alpha APM crystallization) (43% yield). Crystal dissolved in 500ml water. In 45℃ by Dowex 1 x 4 (acetate) columns (1 x 20cm), and 20 ml of water flushing, effluent and washings together vacuum concentration, precipitation of alpha APM crystallization 11.2g. yield of 37%, melting point 235~236℃ (decomposition), than the rotation alpha D22 32.0 ℃ = 1, Cu Suanzhong. Elemental analysis results: 55.30% C, H 6.19%, n 9.36%.
Explosive hazard characteristics
Edible contact dermatitis.
Combustible hazard characteristics
Combustible; combustion produces toxic nitrogen oxide smoke
Storage and transportation characteristics
Combustible; combustion produces toxic nitrogen oxide smoke
Fire extinguishing agent
Dry powder, foam, sand, carbon dioxide, mist water
Originator
Canderel,Searle,France,1979
History
Aspartame was discovered accidentally in 1965 during a search for drugs to treat gastric ulcers. James M. Schlatter, an organic chemist working for G. D. Searle & Company, was using aspartyl-phenylalanine methyl ester (aspartame) in a synthesis procedure and inadvertently got some of the compound on his hands.
Preparation
By coupling the amino acids L-phenylalanine and L-aspartic acid, and the esterification of the carboxyl group of the
phenylalanine moiety to produce the methyl ester. This esterification can occur before or after coupling. The crystallized slurry is
centrifuged and the resulting “wet-cake” is washed to remove impurities.
Production Methods
Aspartame is synthesized using the L enantiomer of phenylalanine. The L enantiomer is separated from the D enantiomer, the racemic mixture, by reacting it with acetic anhydride (CH32
Production Methods
Aspartame is produced by coupling together L-phenylalanine (or Lphenylalanine
methyl ester) and L-aspartic acid, either chemically or
enzymatically. The former procedure yields both the sweet aaspartame
and nonsweet β-aspartame from which the α-aspartame
has to be separated and purified. The enzymatic process yields only
α-aspartame.
Manufacturing Process
A solution of 88.5 parts of L-phenylalanine methyl ester hydrochloride in 100
parts of water is neutralized by the addition of dilute aqueous potassium
bicarbonate, then is extracted with approximately 900 parts of ethyl acetate.
The resulting organic solution is washed with water and dried over anhydrous
magnesium sulfate. To that solution is then added 200 parts of Nbenzyloxycarbonyl-
L-aspartic acid α-p-nitrophenyl, β-benzyl diester, and that
reaction mixture is kept at room temperature for about 24 hours, then at
approximately 65°C for about 24 hours. The reaction mixture is cooled to
room temperature, diluted with approximately 390 parts of cyclohexane, then
cooled to approximately -18°C in order to complete crystallization. The
resulting crystalline product is isolated by filtration and dried to afford β-
benzyl N-benzyloxycarbonyl-L-aspartyl-L-phenylalanine methyl ester, melting
at about 118.5-119.5°C.
To a solution of 180 parts of β-benzyl N-benzyloxycarbonyl-L-aspartyl-Lphenylalanine
methyl ester in 3,000 parts by volume of 75% acetic acid is
added 18 parts of palladium black metal catalyst, and the resulting mixture is
shaken with hydrogen at atmospheric pressure and room temperature for
about 12 hours. The catalyst is removed by filtration, and the solvent is
distilled under reduced pressure to afford a solid residue, which is purified by
recrystallization from aqueous ethanol to yield L-aspartyl-L-phenylalanine
methyl ester. It displays a double melting point at about 190°C and 245-
247°C.
Therapeutic Function
Sugar supplement
Biotechnological Production
Aspartame is produced from L-aspartic acid and L-phenylalanine and methanol or
alternatively L-phenylalanine methyl ester. The standard process uses common
chemical methods of peptide synthesis. Enzymatic coupling of the two amino
acids is also possible. N-formyl-L-aspartic acid and L- or D.L-phenylalanine methyl
ester can be condensed to aspartame by thermolysin-like proteases. The
formylated aspartame can be deformylated chemically or with a formylmethionyl
peptide deformylase to yield the sweetener.The enzymatic coupling does not
require L-phenylalanine but can start from the racemic product obtained in
chemical synthesis, and the remaining D-phenylalanine can be racemized again.
Production processes based on fermentation are available for the two main
components, aspartic acid and phenylalanine.
Pharmaceutical Applications
Aspartame is used as an intense sweetening agent in beverage
products, food products, and table-top sweeteners, and in
pharmaceutical preparations including tablets, powder mixes,
and vitamin preparations. It enhances flavor systems and can be
used to mask some unpleasant taste characteristics; the approximate
sweetening power is 180–200 times that of sucrose.
Unlike some other intense sweeteners, aspartame is metabolized
in the body and consequently has some nutritive value: 1 g provides
approximately 17 kJ (4 kcal). However, in practice, the small
quantity of aspartame consumed provides a minimal nutritive
effect.
Biochem/physiol Actions
Asp-Phe methyl ester (Asp-Phe-OMe) is used as a synthetic sweeter, sugar substitute. Asp-Phe methyl ester is being studied for a variety of potential benefits as a nutrition supplement, such as the delay of osteoarthritis and modulation of rheumatoid factor activity. Asp-Phe methyl ester is being studied for its effect on thrombin activity and blood clotting.
Safety Profile
Human systemic effects byingestion: allergic dermatitis. Experimental reproductiveeffects. When heated to decomposition it emits toxicfumes of NOx.
Safety
Aspartame is widely used in oral pharmaceutical formulations,
beverages, and food products as an intense sweetener, and is
generally regarded as a nontoxic material. However, the use of
aspartame has been of some concern owing to the formation of the
potentially toxic metabolites methanol, aspartic acid, and phenylalanine.
Of these materials, only phenylalanine is produced in
sufficient quantities, at normal aspartame intake levels, to cause
concern. In the normal healthy individual any phenylalanine
produced is harmless; however, it is recommended that aspartame
be avoided or its intake restricted by those persons with
phenylketonuria.
The WHO has set an acceptable daily intake for aspartame at up
to 40 mg/kg body-weight. Additionally, the acceptable daily
intake of diketopiperazine (an impurity found in aspartame) has
been set by the WHO at up to 7.5 mg/kg body-weight.
A number of adverse effects have been reported following the
consumption of aspartame, particularly in individuals who
drink large quantities (up to 8 liters per day in one case) of
aspartame-sweetened beverages. Reported adverse effects include:
headaches; grand mal seizure;memory loss;gastrointestinal
symptoms; and dermatological symptoms. However, scientifically
controlled peer-reviewed studies have consistently failed to
produce evidence of a causal effect between aspartame consumption
and adverse health events. Controlled and thorough studies
have confirmed aspartame’s safety and found no credible link
between consumption of aspartame at levels found in the human
diet and conditions related to the nervous system and behavior, nor
any other symptom or illness. Aspartame is well documented to be
nongenotoxic and there is no credible evidence that aspartame is
carcinogenic.
Although aspartame has been reported to cause hyperactivity
and behavioral problems in children, a double-blind controlled trial
of 48 preschool-age children fed diets containing a daily intake of
38 ± 13 mg/kg body-weight of aspartame for 3 weeks showed no
adverse effects attributable to aspartame, or dietary sucrose, on
children’s behavior or cognitive function.
Environmental Fate
Aspartame is nontoxic. However, individuals with the rare,
genetic disease, phenylketonuria (PKU), cannot properly
metabolize phenylalanine. Such individuals are detected by
testing at birth and placed on special low-phenylalanine diets
to control their blood phenylalanine concentrations. Thus,
PKU individuals need to be aware that aspartame is a source of
phenylalanine.
Metabolic pathway
The rate of aspartame degradation is faster in a
phosphate buffer solution than in a citrate buffer
solution at the same pH and buffer concentration. The
primary mechanism by which aspartame degrades, the
formation of diketo piperazine, involves the
nucleophilic attack of carbonyl by the free amine,
which requires proton transfer.
storage
Aspartame is stable in dry conditions. In the presence of moisture,
hydrolysis occurs to form the degradation products L -aspartyl-Lphenylalanine
and 3-benzyl-6-carboxymethyl-2,5-diketopiperazine
with a resulting loss of sweetness. A third-degradation product is
also known, β-L-aspartyl-L-phenylalanine methyl ester. For the
stability profile at 258℃ in aqueous buffers.
Stability in aqueous solutions has been enhanced by the addition
of cyclodextrins, and by the addition of polyethylene glycol 400
at pH 2. However, at pH 3.5–4.5 stability is not enhanced by the
replacement of water with organic solvents.
Aspartame degradation also occurs during prolonged heat
treatment; losses of aspartame may be minimized by using processes
that employ high temperatures for a short time followed by rapid
cooling.
The bulk material should be stored in a well-closed container, in
a cool, dry place.
Incompatibilities
Differential scanning calorimetry experiments with some directly
compressible tablet excipients suggests that aspartame is incompatible
with dibasic calcium phosphate and also with the lubricant
magnesium stearate. Reactions between aspartame and sugar
alcohols are also known.
Regulatory Status
Accepted for use as a food additive in Europe and in the USA.
Included in the FDA Inactive Ingredients Database (oral powder for
reconstitution, buccal patch, granules, syrups, and tablets).
Included in nonparenteral medicines licensed in the UK. Included
in the Canadian List of Acceptable Non-medicinal Ingredients.
Check Digit Verification of cas no
The CAS Registry Mumber 22839-47-0 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 2,2,8,3 and 9 respectively; the second part has 2 digits, 4 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 22839-47:
(7*2)+(6*2)+(5*8)+(4*3)+(3*9)+(2*4)+(1*7)=120
120 % 10 = 0
So 22839-47-0 is a valid CAS Registry Number.
InChI:InChI=1/C14H18N2O5/c1-21-14(20)11(7-9-5-3-2-4-6-9)16-13(19)10(15)8-12(17)18/h2-6,10-11H,7-8,15H2,1H3,(H,16,19)(H,17,18)/t10-,11-/m0/s1
22839-47-0Relevant articles and documents
A SUPERIOR SYNTHESIS OF ASPARTAME
Vinick, Fredic J.,Jung, Stanley
, p. 1315 - 1318 (1982)
The dipeptide sweetener aspartame has been prepared in high yield via the coupling of L-phenylalanine methyl ester and L-aspartic acid N-thiocarboxyanhydride.
Investigation of solid-state reactions using variable temperature X-ray powder diffractrometry. I. Aspartame hemihydrate
Rastogi,Zakrzewski,Suryanarayanan
, p. 267 - 273 (2001)
Purpose. The object of this study was to demonstrate the applicability of variable temperature X-ray powder diffractometry (XRD) to investigate solid-state reactions using aspartame as a model compound. Methods. Aspartame exists as a hemihydrate (ASH) under ambient conditions and converts to aspartame anhydrate (ASA) at ～130°C. ASA on further heating to ～180°C undergoes decomposition (intramolecular cyclization) to form a diketopiperazine derivative (DKP). The dehydration as well as the decomposition kinetics were studied isothermally at several temperatures. The unique feature of this technique is that it permits simultaneous quantification of the reactant as well as the product. Results. While the dehydration of ASH appeared to follow first-order kinetics, the cyclization of ASA was a nucleation controlled process. The rate constants were obtained at various temperatures, which permitted the calculation of the activation energies of dehydration and cyclization from the Arrhenius plots. The activation energy of dehydration was also calculated according to the method described by Ng (Aust. J. Chem., 28:1169-1178, 1975) and the two values were in good agreement. Conclusions. The study demonstrates that XRD is an excellent complement to thermal analysis and provides direct information about the solid-states of various reaction phases.
Molecularly imprinted polymeric adsorbents for byproduct removal
Ye, Lei,Ramstroem, Olof,Mosbach, Klaus
, p. 2789 - 2795 (1998)
In this study, both diastereo- and enantioselective adsorbents for a dipeptide derivative were prepared using a molecular imprinting technique. The diastereo- and enantioisomers for the dipeptide derivative N-(benzyloxycarbonyl)aspartylphenylalanine methyl ester (ZAPM), in addition to the α- and β-isomers, were chosen as test compounds for the investigation of the imprinting effect. The close similarities between the structures of different isomers make it possible to interpret the roles of template structure on specific molecular recognition. A highly specific byproduct scavenger was prepared by simultaneously incorporating methacrylic acid and vinylpyridine as functional monomers. The binding selectivities of polymeric adsorbents for the α- and β-isomers are shown to be greatly enhanced by introducing enantiocomplementarities into the polymer matrixes. An anti-β-L,L-ZAPM polymer was applied in a solid-phase extraction protocol, for the purification of the product in the chemical synthesis of N-protected aspartame. Finally, polymer beads were also imprinted against β-L,L-ZAPM using suspension polymerization performed in perfluorocarbon fluid. The imprinted polymer beads displayed the same binding characteristics as the imprinted bulk polymer and can be envisaged for the use of product purification in chromatographic mode.
STUDIES ON AMINO ACIDS AND PEPTIDES - VII SYNTHESES OF ASPARTAME AND THIOASPARTAME
Yde, B.,Thomsen, I.,Thorsen, M.,Clausen,K.,Lawesson, S.-O.
, p. 4121 - 4126 (1983)
The protected aspartame, 4, has been prepared from the benzyl ester of N-benzyloxycarbonyl-S-aspartic acid, 1, and the methyl S-phenylalanate, 3, using 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide, LR, as a coupling reagent.Another protected aspartame, 7, has been prepared from the tert-butyl ester of 1--succinimide, 6, and methyl S-phenylalanate, 3.Thiations of 4/7 by LR produces a protected thioaspartame, 5/9.Deprotection of 7 and 9 gives aspartame, 8, and the slightly sweet thioaspartame, 10, in high yields.
Synthesis of β-lactam peptidomimetics through Ugi MCR: First application of chiral Nβ-Fmoc amino alkyl isonitriles in MCRs
Vishwanatha,Narendra,Sureshbabu, Vommina V.
experimental part, p. 5620 - 5624 (2011/11/06)
Chiral Nβ-Fmoc amino alkyl isonitriles were employed in Ugi multi component reactions (Ugi 4C-3CR) to obtain functionalized β-lactam peptidomimetics with l-aspartic acid α-methyl ester/peptide ester and organic aldehydes. The reactions were carried out in MeOH. Thirteen Ugi products have been prepared in good to moderate yields with good diastereoselectivities.
METHOD FOR THE SYNTHESIS OF PEPTIDES WITHOUT SOLVENT
-
Page/Page column 6, (2010/02/17)
The disclosure relates to a method for the synthesis of a compound of the formula (I) in which: n is an integer higher than or equal to 1; Rb and each Rn are independently a hydrogen atom, a C1-C6 arylalkyl group or a C1-C6 alkyl group substituted or not by an aryl group, —COOH, C1-C6, —COO-(alkyl), —CONH2, —SH, heteroaryl, —NH2, —NHC(NH)(NH2), C1-C6-s-(alkyl), —OH or phenol; Ra is a N-protective group; Rc is a ORd group in which Rd is a C1-C6 alkyl group or a NReRf group in which Re and Rf Re independently an N-protective group.
Solvent-free synthesis of peptides
Declerck, Valerie,Nun, Pierrick,Martinez, Jean,Lamaty, Frederic
supporting information; experimental part, p. 9318 - 9321 (2010/03/24)
Chamical Equation Presentation A crush on sweetness! The coupling of a urethane-protected N-carboxyanhydride of an amino acid with another amino acid derivative under ball-milling conditions gives a protected dipeptide in very high yield (see scheme; PG: protecting group). The reaction takes place in the solid state. The synthesis was applied to the preparation of a tri peptide and the sweetener aspartame, without any organic solvent or purification.
Hexafluoroacetone as protection and activation reagent in amino acid and peptide chemistry regiospecific α-functionalization of aspartic acid
Burger, Klaus,Lange, Torsten,Rudolph, Martin
, p. 189 - 198 (2007/10/03)
A highly efficient method for regiospecific α-functionalization of aspartic acid is described. Key step is the synthesis of a N-protected and regioselectively α-carboxy-activated heterocyclic intermediate from aspartic acid and hexafluoroacetone. The new strategy offers i.a. a two step access to the sweetener Aspartame and to libraries of aspartame analogues.
Porous pharmaceutical form and its preparation
-
, (2008/06/13)
New porous, unitary freeze-dried pharmaceutical form, of homogeneous appearance, consisting of: a) an inclusion compound comprising: one or optionally more active substances, a predetermined quantity of cyclodextrin, optionally an additive facilitating inclusion, b) at least one substance chosen from: diluents, binders; and c) optionally one or more additives.
Process for the drying and granulation of aspartame
-
, (2008/06/13)
The invention relates to a process for the drying and granulation of aspartame through the thermal treatment of a wet mass of aspartame crystals using a hot carrier gas, characterised in that a wet mass of aspartame crystals is supplied, in a continuous process, to a high-speed paddle dryer fitted with a jacket heated to a temperature of 80-190°C and with paddles, mounted on a central shaft with a controllable speed of rotation, at an adjustable distance from and angle to the jacket, which are positioned so that the required particle size of the granules is realized, the speed of rotation being chosen so that the Froude number is higher than 1, and the supplied product is treated in the paddle dryer for 15-600 seconds, with the simultaneous presence of a carrier gas having an inlet temperature of 100-200°C, and the granular product obtained is discharged from the paddle dryer and, if necessary, dried further - in a manner known per se - in one or more drying steps in other drying equipment. With the use of high-speed paddle dryer aspartame with good microbiological properties is very easily obtained.
