Ajinomoto Co., Ltd.

Kazutaka Nagashima

Tadashi Takemoto

Akihiro Kishishita

Shigeru Kawahara

Eriko Ono

Yuuichi Aoki

Takeshi Nagai

Hirotoshi Ishida

Atsuhiko Hirano

Kenichi Mori

Yusuke Amino

Toyoto Hijiya

Satoji Takahashi

Nao Funakoshi

Shinji Fujita

Chiaki Mochizuki

A crystallization process for forming a stable crystal of N-(3,3-dimethylbutyl)-APM, which comprises using either water or a mixture of water with a lower alcohol as the crystallizing solvent and controlling the crystallization point to 30&#xb0; C. or above; and another crystallization process therefor, which comprises using either water or a mixture of water with a lower alcohol as the crystallizing solvent and using as the seed crystal a crystal of N-(3,3-dimethylbutyl)-APM exhibiting peculiar peaks of diffracted X-ray at least at diffraction angles (2&#x3b8;, CuK&#x3b1; ray) of 6.0&#xb0;, 24.8&#xb0;, 8.2&#xb0; and 16.5&#xb0; to thereby crystallize the above objective crystal preferentially. These crystallization processes enable the constant formation of stable crystals of N-(3,3-dimethylbutyl)-APM at a low cost.

Crystallization processes for the formation of stable crystals of aspartame derivative

Disclosed in the present application are a method for preparing highly-stable A-type crystals by controlling and maintaining the product temperature of B-type N-(3,3-dimethylbutyl)-APM crystals at 25 to 80&#xb0; C. under an absolute humidity of 0.203 kg/kg or less environment, thereby effecting crystal transition; and a method for preparing A-type crystals by controlling and maintaining the product temperature of D-type crystals of N-(3,3-dimethylbutyl)-APM at 25 to 80&#xb0; C. under an absolute humidity of 0.0550 kg/kg or less environment, thereby effecting crystal transition. According to these crystal transition methods, highly stable crystals can be prepared stably and at a low cost.

Method for preparing highly stable crystals of aspartame derivative

N-[N-[3-(2-hydroxy-substituted phenyl)propyl]-L-&#x3b1;-aspartyl]-L-phenylalanine 1-methyl ester derivatives, which are useful as sweeteners, may be conveniently produced by subjecting a 2-hydroxychroman derivative having various substituents on the benzene ring and aspartame to a reductive alkylation reaction. These compounds may be purified by subjecting such a derivative containing one or more impurities to a crystallization step to crystallize the same. Further, there are provided a process for producing dialkoxychroman derivatives useful as intermediates for the production of such aspartame derivatives in the above process, and novel dialkoxychroman derivatives thus produced, which are excellent as the production intermediate.

Process for producing aspartame derivatives, process for purifying aspartame derivatives, production intermediates, and process for producing production intermediates

N-&lsqb;N-&lsqb;3-(phenyl having various substituent group(s) on the benzene ring)propyl&rsqb;-L-&agr;-aspartyl&rsqb;-L-phenylalanine 1-methyl ester derivatives, which are useful as sweeteners, may be conveniently produced on an industrial scale at a high yield by reductively alkylating aspartame with a 3-(phenyl having specified substituent group(s) on the benzene ring)-2-propenyl aldehyde and hydrogen in the presence of a catalyst and a base.

Process for production of aspartyl dipeptide ester derivatives

N-&lsqb;N-&lsqb;3-(3-hydroxy-4-methoxyphenyl)propyl&rsqb;-L-&agr;-aspartyl&rsqb;-L-phenylalanine 1-methyl ester useful as a sweetener with a high potency of sweetness, is provided in the crystalline form having a high stability and a good purity which is favorable as a commercial product.

Crystals of aspartame derivative

The present invention relates to a method of manufacturing aspartyl dipeptide ester compounds, which can be used as sweeteners, and aldehydes that can be used in the manufacturing processes.

Process for production of aspartyl dipeptide ester derivative, novel production intermediate therefor, and process for production thereof

For example, N-&lsqb;N-(3,3-dimethylbutyl)-L-&agr;-aspartyl&rsqb;-L-phenylalanine methyl ester (A-type crystal) showing characteristic peaks in diffractive X-ray at diffraction angles (2&thgr;, CuK&agr; ray) of at least 6.0&deg;, 24.8&deg;, 8.2&deg; and 16.5&deg; is dried to its water content below 3% by weight. The crystal thus dried is a novel crystal (C-type crystal) of N-&lsqb;N-(3,3-dimethylbutyl)-L-&agr;-aspartyl&rsqb;-L-phenylalanine methyl ester excellent in dissolution rate, and when measured by powder X-ray diffractometry, this crystal shows characteristic peaks in diffractive X-ray at diffraction angles (2&thgr;, CuK&agr; ray) of at least 7.1&deg;, 19.8&deg;, 17.3&deg; and 17.7&deg;. The dissolution rate (solubility) of the C-type crystals is further improved by converting the crystals into granules.

Aspartame derivative crystal and process for producing the same

The present invention relates to a 3-substituted-phenyl-3-merthylbutyric acid and 3-substituted-phenyl-3-merthylaldehyde derivatives, which are useful in the production of N-&lsqb;N-&lsqb;3-(3-hydroxy-4-methoxyphenyl)-3-methylbutyl&rsqb;-L-&agr;-aspartyl&rsqb;-L-phenylalanine 1-methyl ester, which is a sweetener with high sweetening potency.

Intermediate for sweetener with high sweetness and process for producing the same

A process for easily and efficiently separating aspartame (APM) from N-&lsqb;N-(3,3-dimethylbutyl)-L-(&agr;-aspartyl&rsqb;-L-phenylalanine methyl ester (APM derivative), and thus separating and purifying the APM and the above-mentioned APM derivative, more specifically the N-(3,3-dimethylbutyl)-APM each at a high purity, which comprises subjecting an aqueous solution containing the APM and the APM derivative, to column chromatography using a nonpolar highly porous polymer based resin.

Process for separating and purifying aspartame and a derivative thereof

Herein are disclosed a process for producing xylitol of high purity (one-step desalting process) which comprises the steps of (1) removing the solid matter from a culture froth obtained by culturing a xylitol-producing microorganism in an aqueous culture medium, (2) desalting the resulting solid matter-removed culture broth by removing the ionic substances therefrom by means of a cation-exchange resin and an anion-exchange resin, (3) subjecting the resulting desalted solution to the chromatography using a strongly acidic cation-exchange resin to separate the xylitol from the other sugar alcohol(s) and sugar(s), and (4) obtaining the xylitol by separating it at a high purity from the resulting xylitol solution (fraction), and to a similar process (two-step desalting process) but wherein the desalting carried out twice by adding the ion-exclusion step between Steps (1) and (2) of the above-mentioned process, whereby most of the ionic substances are removed, by which processes highly pure xylitol can be obtained from a xylitol solution in a commercially effective way, in the method for producing xylitol by using a xylitol-producing microorganism.

Process for producing xylitol of high purity

A homogeneous sweetener composition containing aspartame (APM) and N-&lsqb;N-(3,3-dimethylbutyl)-L-&agr;-aspartyl&rsqb;-L-phenylalanine methyl ester having tasting properties similar to sucrose, can be efficiently produced in high yields and with a high purity by reductive alkylation of APM with an at most equimolar amount 3,3-dimethylbutylaldehyde followed by separating the reducing agent from the liquid reaction mixture, and separating of the precipitated crystals of the sweetener composition.

Sweetener compositions containing aspartame and aspartame derivative

One embodiment of the present invention provides a sweetener composition, which includes a mixture of N-&lcub;N-(3,3-dimethylbutyl)-L-&agr;-aspartyl&rcub;-L-phenylalanine 1-methyl ester, and Acesulfame K, wherein a ratio of the Acesulfame K to a total amount of the N-&lcub;N-(3,3-dimethylbutyl)-L-&agr;-aspartyl&rcub;-L-phenylalanine 1-methyl ester and the Acesulfame K is in the range of 10 to 97% by weight, methods of making and of using. Another embodiment of the present invention provides a method for preparing a sweetener composition, which includes drying an A-type crystal of N-&lcub;N-(3,3-dimethylbutyl)-L-&agr;-aspartyl&rcub;-L-phenylalanine 1-methyl ester to obtain a C-type crystal of N-&lcub;N-(3,3-dimethylbutyl)-L-&agr;-aspartyl&rcub;-L-phenylalanine 1-methyl ester. Another embodiment of the present invention provides a method for producing a sweetener, which includes admixing N-&lcub;N-(3,3-dimethylbutyl)-L-&agr;-aspartyl&rcub;-L-phenylalanine 1-methyl ester with Acesulfame K, wherein a ratio of the Acesulfame K to a total amount of the N-&lcub;N-(3,3-dimethylbutyl)-L-&agr;-aspartyl&rcub;-L-phenylalanine 1-methyl ester and the Acesulfame K is in the range of 10 to 97% by weight. Another embodiment of the present invention provides a method for improving the dissolution rate of N-&lcub;N-(3,3-dimethylbutyl)-L-&agr;-aspartyl&rcub;-L-phenylalanine 1-methyl ester, which includes, prior to dissolving the N-&lcub;N-(3,3 -dimethylbutyl)-L-&agr;-aspartyl&rcub;-L-phenylalanine 1-methyl ester, admixing the N-&lcub;N-(3,3-dimethylbutyl)-L-&agr;-aspartyl&rcub;-L-phenylalanine 1-methyl ester with Acesulfame K, wherein a ratio of the Acesulfame K to a total amount of the N-&lcub;N-(3,3-dimethylbutyl)-L-&agr;-aspartyl&rcub;-L-phenylalanine 1-methyl ester and the Acesulfame K is in the range of 10 to 97% by weight.

Sweetener composition

One embodiment of the present invention provides a sweetener composition, which includes N-&lcub;N-(3,3-dimethylbutyl)-L-&agr;-aspartyl&rcub;-L-phenylalanine 1-methyl ester, and Aspartame, wherein a ratio of the Aspartame to a total amount of the Aspartame and the N-&lcub;N-(3,3-dimethylbutyl)-L-&agr;-aspartyl&rcub;-L-phenylalanine 1-methyl ester is in the range of 10 to 99.5% by weight, methods of making and of using. Another embodiment of the present invention provides a method for preparing a sweetener composition, which includes drying an A-type crystal of N-&lcub;N-(3,3-dimethylbutyl)-L-&agr;-aspartyl &rcub;-L-phenylalanine 1-methyl ester to obtain a C-type crystal of N-&lcub;N-(3,3-dimethylbutyl)-L-&agr;-aspartyl &rcub;-L-phenylalanine 1-methyl ester. Another embodiment of the present invention provides a method for producing a sweetener, which includes admixing N-&lcub;N-(3,3-dimethylbutyl)-L-&agr;-aspartyl &rcub;-L-phenylalanine 1-methyl ester with Aspartame, wherein a ratio of the Aspartame to a total amount of the N-&lcub;N-(3,3-dimethylbutyl)-L-&agr;-aspartyl &rcub;-L-phenylalanine 1-methyl ester and the Aspartame is in the range of 10 to 99.5% by weight. Another embodiment of the present invention provides a method for improving the dissolution rate of N-&lcub;N-(3,3-dimethylbutyl)-L-&agr;-aspartyl &rcub;-L-phenylalanine 1-methyl ester, which includes, prior to dissolving the N-&lcub;N-(3,3-dimethylbutyl)-L-&agr;-aspartyl &rcub;-L-phenylalanine 1-methyl ester, admixing the N-&lcub;N-(3,3-dimethylbutyl)-L-&agr;-aspartyl &rcub;-L-phenylalanine 1-methyl ester with Aspartame, wherein a ratio of the Aspartame to a total amount of the N-&lcub;N-(3,3-dimethylbutyl)-L&agr;-aspartyl&rcub;-L-phenylalanine 1-methyl ester and the Aspartame is in the range of 10 to 99.5% by weight.

Mixed crystals comprising aspartame and aspartame derivative and process for producing the same

Addition of a reaction mixture obtained by the mineral acid hydrolysis of at least one side flow generated from the production of .alpha.-L-aspartyl-L-phenylalanine methyl ester to a crystallization slurry containing L-phenylalanine while maintaining the pH of the slurry at 3-8 by adding aqueous alkali affords crystallized L-phenylalanine having a low water content in a high yield.

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Kawasaki, Japan

Kazutaka Nagashima