55102-13-1

Usage

InChI:InChI=1/C13H14N2O4/c16-11(17)7-10-13(19)14-9(12(18)15-10)6-8-4-2-1-3-5-8/h1-5,9-10H,6-7H2,(H,14,19)(H,15,18)(H,16,17)

Upstream product

• 22839-47-0 L-Asp-L-Phe-OMe 
• 3918-98-7 Asp-Phe-OH 
• 56633-51-3 N-formyl-L-α-aspartyl-L-phenylalanine 
• 120295-14-9 (5-benzyl-3,6-dioxo-piperazin-2-yl)-acetic acid methyl ester 

Relevant academic research and scientific papers

Hydration and dehydration behavior of aspartame hemihydrate

Previous studies have shown that aspartame in the solid state can exist as a hemihydrate which occurs in two different polymorphic forms (I and II). The present work shows that equilibration of either hemihydrate at 25 °C with water vapor at relative humidities ≤58% or with liquid water produces a 2.5-hydrate. Upon subjecting each of these crystalline hydrates to increasing temperature, the same crystalline anhydrate is formed which thermally cyclizes at a higher temperature to form the known compound 3- (carboxymethyl)-6-benzyl-2,5-dioxopiperazine. The activation energy of the cyclization reaction appears to depend on the degree of crystallinity of the anhydrate that is formed at a lower temperature. On increasing the temperature of the 2.5-hydrate, a hemihydrate intervenes before the anhydrate is formed. This intervening hemihydrate is similar to the commercial form (11) of aspartame hemihydrate but exhibits greater amorphous character. The techniques employed were Karl Fischer titrimetry, powder X-ray diffractometry, differential scanning calorimetry, thermogravimetric analysis, solid-state 13C nuclear magnetic resonance spectroscopy, and Fourier transform infrared absorption spectroscopy.

Isothermal Fourier transform infrared microspectrosopic studies on the stability kinetics of solid-state intramolecular cyclization of aspartame sweetener

A novel Fourier transform infrared (FT-IR) microspectrophotometer equipped with differential scanning calorimetry (DSC) was used to investigate the kinetics of intramolecular cyclization of aspartame (APM) sweetener in the solid state under isothermal conditions. The thermal-dependent changes in the peak intensity of IR spectra at 1543, 1283, and 1259 cm-1 were examined to explore the reaction. The results support that the intramolecular cyclization process in APM proceeded in three steps: the methoxyl group of ester was first thermolyzed to release methanol, then an acyl cation was attacked by the lone pair of electrons available on nitrogen by an S(N)1 pathway, and finally ring-closure occurred. The intramolecular cyclization of APM determined by this microscopic FT-IR/DSC system was found to follow zero- order kinetics after a brief induction period. The bond cleavage energy (259.38 kJ/mol) of thermolysis for the leaving group of -OCH3, the bond conversion energy (328.88 kJ/mol) for the amide II NH band to DKP NH band, and the CN bond formation energy (326.93 kJ/mol) of cyclization for the DKP in the APM molecule were also calculated from the Arrhenius equation. The total activation energy of the DKP formation via intramolecular cyclization was 261.33 kJ/mol, calculated by the above summation of the bond energy of cleavage, conversion, and formation, which was near to the value determined by the DSC or TGA method. This indicates that the microscopic FT-IR/DSC system is useful as a potential tool not only to investigate the degradation mechanism of drugs in the solid state but also to directly predict the bond energy of the reaction.

Solid State Stability Studies of Model Dipeptides: Aspartame and Aspartylphenylalanine

Some solid-state pharmaceutical properties and the solid-state thermal stability of the model dipeptides aspartame (APM) and aspartylphenylalanine (AP), have been investigated, Studies by differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), high-performance liquid chromatography, powder X-ray diffraction, and optical microscopy have shown that the dipeptides undergo solid state intramolecular aminolysis of the type, solid → solid + gas. This reaction was observed for APM at 167-180°C with the liberation of methanol and for AP at 186-202°C with the liberation of water. The exclusive solid product of the degradation reaction of both dipeptides is the cyclic compound 3-(carboxymethyl)-6-benzyl-2,5-dioxopiperazine, The rates of the degradation reactions were monitored by isothermal TGA and by temperature-ramp DSC and were found to follow kinetics based on nucleation control with activation energies of about 266 kJ mol-1 for APM and 234 kJ mol-1 for AP.

Aspartame Decomposition and Epimerization in the Diketopiperazine and Dipeptide Products as a Function of pH and Temperature

Cyclization and hydrolysis of aspartame were studied over a range of pH and temperatures by using an HPLC method which allows simultaneous analysis of the diastereomeric dipeptide and diketopiperazine products.The pH dependence of aspartic acid and phenylalanine racemization rates in the dipeptide-diketopiperazine system resulting from aspartame decomposition was determined.On the basis of these studies a general scheme of relative epimerization rates of amino acids in diketopiperazines and in the various positions and ionic states of peptides is presented.This scheme is discussed in terms of the carbanion mechanism of amino acid racemization and found to be consistent with it.Racemization rates in the diketopiperazine were greater than those of all ionic forms of the free amino acids and dipeptides except for fully protonated free amino acids and protonated terminal amino acids of peptides.In the neutral pH range the relative racemization rates in the DKP and dipeptides were DKP > amino terminal > carboxy terminal.Apparently contradictory results reported in the literature from dipeptide heating experiments were reanalyzed in terms of dipeptide-diketopiperazine-inverted dipeptide conversion.Viewed in this light, the literature is self-consistent and supports the generality of our scheme of relative racemization rates and mechanistic conclusions.

Investigations on the degradation of aspartame using high-performance liquid chromatography/tandem mass spectrometry

Aspartame is a widely used sweetener, the long-term safety of which has been controversial ever since it was accepted for human consumption. It is unstable and can produce some harmful degradation products under certain storage conditions. A high-performa

Solvent effects on chemical processes. 8. Demethylation kinetics of aspartame in binary aqueous-organic solvents

The kinetics of demethylation of aspartame were studied in binary aqueous- organic solvent mixtures at 25 Γ under two solution conditions, namely 1.0 M HCI (pH 0.28 in water) and carbonate buffer (pH 10.1 in water). Under these conditions solvent effects

Preparation process of α-L-aspartyl-L-phenylalanine methyl ester or hydrochloride thereof

Disclosed herein is a process for preparing α-L-aspartyl-L-phenylalanine methyl ester or its hydrochloride from 5-benzyl-3,6-dioxo-2-piperazine acetic acid or its methyl ester, prepared without using L-penylalanine methyl ester which involves problems in