KR890003252B1 - Process for-alpha-l-aspartyl-l-penylal alarninester - Google Patents

Process for-alpha-l-aspartyl-l-penylal alarninester Download PDF

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KR890003252B1
KR890003252B1 KR1019870001357A KR870001357A KR890003252B1 KR 890003252 B1 KR890003252 B1 KR 890003252B1 KR 1019870001357 A KR1019870001357 A KR 1019870001357A KR 870001357 A KR870001357 A KR 870001357A KR 890003252 B1 KR890003252 B1 KR 890003252B1
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aspartyl
methyl ester
phenylalanine methyl
penylal
alarninester
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KR880009584A (en
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김선태
연성열
홍영기
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제일제당 주식회사
손영희
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/10—Natural spices, flavouring agents or condiments; Extracts thereof

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Abstract

A method for preparing α -L-aspartyl-L-phenylalanine methyl ester is presented. Thus, 300g α -thiosalicyl-L-asparagine in anhyd. acetic acid was reacted with 210g α-phenylalanine methyl ester in methanol contg. triethylene amine at 50≰C for 6hr. The mixt. was treated with 500ml 0.1N-HCl to give L-aspartyl-L-phenylalanyl methyl ester, which was neutralized with 0.1N NaOH to give final product (Yield=75%).

Description

α-L-아스파틸-L-페닐알라닌메틸에스테르의 제조방법Method for preparing α-L-aspartyl-L-phenylalanine methyl ester

본 발명은 아스파탐이라고 불리워지고 있는 인공감미료인 α-L-아스파틸-L-페닐알라닌메틸에스테르의 제조방법에 관한 것이다.The present invention relates to a method for producing α-L-aspartyl-L-phenylalanine methyl ester, which is an artificial sweetener called aspartame.

일반적으로 아스파탐은 설탕의 200배에 상당하는 감미를 지닌 저칼로리의 인공감미료로서 많이 사용되는 물질로 인체대사에 적합한 것으로 알려져 있다.In general, aspartame is a low-calorie artificial sweetener with a sweetness equivalent to 200 times the sugar. It is known to be suitable for human metabolism.

종래에는 L-아스파라긴산을 삼염화인, 포름알데히드등의 물질과 반응시킨 다음 페닐알라닌에스테르와 축합시켜 아스파탐을 제조하고 있으나, 이러한 방법에서는 아스파라긴산의 α위치및β위치에 카르복실기가 모두 반응에 참여하게 되어 라세미화가 일어나 α체 및β체의 물질이 생성되는 단점이 있다.Conventionally, aspartame is prepared by reacting L-aspartic acid with a substance such as phosphorus trichloride or formaldehyde, and then condensing with phenylalanine ester, but in this method, carboxyl groups participate in the reaction at both the α and β positions of aspartic acid. There is a disadvantage in that a substance of α and β forms is generated.

이 방법에서 생성된 β-L-아스파틸-L-페닐알라닌메틸에스테르는 감미 효과가 없을 뿐만 아니라, α체의 순도를 저하시키므로서 분리정제 공정이 필요하게 됨은 물론, 목적물의 순도를 저하시키는 문제점이 있었다.The β-L-aspartyl-L-phenylalanine methyl ester produced by this method not only has no sweetening effect, but also requires a separate purification process by lowering the purity of the α-body, and also reduces the purity of the target product. there was.

따라서 본 발명자등은 종래방법의 문제점을 개선하고자 연구 노력한 결과, 상술한 바와같은 단점을 개선한 본 발명을 완성하게 되었다.Therefore, the present inventors, as a result of research efforts to improve the problems of the conventional method, have completed the present invention to improve the disadvantages described above.

즉, 본 발명은 아스파라긴산의 아미노기를 티오살리실산으로 보호하여 L-페닐알라닌메틸에스테르와 반응시킬 경우에 순도가 높은 α-L-아스파틸-L-페닐알라닌메틸에스테르를 제조할 수 있으며 티오살리실산으로 아미노기를 보호하여 제조한 티오살리실아스파라긴 무수물은 분자내의 극성으로 인하여 축합반응시 β체 생성이 억제됨을 발견함으로써 완성된 것이다.That is, the present invention can prepare high purity α-L-aspartyl-L-phenylalanine methyl ester when the amino group of aspartic acid is protected with thiosalicylic acid and reacted with L-phenylalanine methyl ester, and the amino group is protected with thiosalicylic acid. The thiosalicylic asparagine anhydride prepared by the present invention was completed by finding that β-formation is inhibited during the condensation reaction due to the polarity in the molecule.

또한, 본 발명에서는 중화제로 메틸디아민 또는 암모니아수와 하이드라진을 10:1의 비율로 혼합한 용액을 사용하였으며, 반응을 촉진시키기 위하여 미량의 Zn을 사용하고 30-35℃의 온도에서 3-10시간 반응시켰다.In addition, in the present invention, a mixture of methyldiamine or ammonia water and hydrazine in a ratio of 10: 1 was used as a neutralizing agent, and a small amount of Zn was used to promote the reaction and reacted at a temperature of 30-35 ° C. for 3-10 hours. I was.

본 발명을 반응식으로 표현하면 다음과 같다.Expressed by the reaction scheme as follows.

Figure kpo00001
Figure kpo00001

다음의 실시예에서 본 발명을 좀더 구체적으로 설명한다.The present invention is explained in more detail in the following examples.

[실시예 1]Example 1

α-티오살리실-L-아스파라긴산 300g을 무수초산 용매에서 용해한 다음, 별도로 제조한 α-페닐알라닌메틸에스테르 210g을 트리에틸렌아민을 첨가한 메탄올용액 내에서 50℃의 온도로 교반하면서 6시간 반응시켰다.After dissolving 300 g of α-thiosalicyl-L-aspartic acid in acetic anhydride solvent, 210 g of separately prepared α-phenylalanine methyl ester was reacted for 6 hours with stirring at a temperature of 50 ° C. in a methanol solution to which triethyleneamine was added.

반응이 완료되면 물 및 유기용매 내에서 미량의 Zn을 촉매로 하여 0.1N의 HCI을 500ml 첨가하므로써 L-아스파틸-L-페닐알라니메틸에스테르를 유리시킨 다음, 0.1M의 NaOH로 중화시키고 공지의 방법으로 정제하여 75%의 수율로 α-L-아스파틸-L-페닐알라닌메틸에스테르를 얻었다.After the reaction was completed, L-aspartyl-L-phenylalanylmethyl ester was liberated by adding 500 ml of 0.1 N HCI as a catalyst in water and an organic solvent, followed by neutralization with 0.1 M NaOH, and known. Purification was carried out to obtain α-L-aspartyl-L-phenylalanine methyl ester in a yield of 75%.

[실시예 2]Example 2

촉매로 미량의 Zn을 사용하고 중화제로 수산화암모늄과 하이드라진이 10:1로 혼합된 용액을 사용한 것을 제외하고는 실시예 1과 같은 방법을 행하였다.The same method as in Example 1 was carried out except that a small amount of Zn was used as a catalyst and a solution containing 10: 1 of ammonium hydroxide and hydrazine as a neutralizing agent was used.

Claims (1)

아스파라긴산의 아미노기를 티오살리실산으로 보호한 다음, 페닐알라닌메틸에스테르와 축합시킴을 특징으로 하는 α-L-아스파틸-L-페닐알라닌메틸에스테르의 제조방법.A method for producing α-L-aspartyl-L-phenylalanine methyl ester, characterized in that the amino group of aspartic acid is protected with thiosalicylic acid and then condensed with phenylalanine methyl ester.
KR1019870001357A 1987-02-18 1987-02-18 Process for-alpha-l-aspartyl-l-penylal alarninester KR890003252B1 (en)

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