WO2003072587A1 - Procédé de préparation de composé de thiazolidine non volatil - Google Patents

Procédé de préparation de composé de thiazolidine non volatil Download PDF

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Publication number
WO2003072587A1
WO2003072587A1 PCT/JP2003/001362 JP0301362W WO03072587A1 WO 2003072587 A1 WO2003072587 A1 WO 2003072587A1 JP 0301362 W JP0301362 W JP 0301362W WO 03072587 A1 WO03072587 A1 WO 03072587A1
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WO
WIPO (PCT)
Prior art keywords
producing
thiazolidine
compound
cysteine
thiazolidine compound
Prior art date
Application number
PCT/JP2003/001362
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English (en)
Japanese (ja)
Inventor
Hirokazu Kawaguchi
Masanori Kohmura
Original Assignee
Ajinomoto Co., Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Application filed by Ajinomoto Co., Inc. filed Critical Ajinomoto Co., Inc.
Priority to AU2003207194A priority Critical patent/AU2003207194A1/en
Priority to JP2003571293A priority patent/JPWO2003072587A1/ja
Publication of WO2003072587A1 publication Critical patent/WO2003072587A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H9/00—Compounds containing a hetero ring sharing at least two hetero atoms with a saccharide radical
    • C07H9/06—Compounds containing a hetero ring sharing at least two hetero atoms with a saccharide radical the hetero ring containing nitrogen as ring hetero atoms

Definitions

  • the present invention relates to a novel method for producing a non-volatile thiazolidine compound which can be produced in a short time and at a high yield and has no problem for food use.
  • a non-volatile thiazolidine compound is useful for enhancing the flavor or improving the flavor of foods and drinks by enhancing the flavor and masking of unpleasant odors, and based on such findings, ⁇ Enhancing the flavor of foods and beverages '' Or a method for enhancing or improving the flavor of foods and beverages using the composition and the method for improving or improving the flavor of the food and drink using the composition (International Application No. PCT / JP01 / 077769 (WO 02/2)). 1 9 3 8 A 1)
  • An object of the present invention is to provide a production method capable of obtaining a non-volatile thiazolidine conjugate having utility as described in the preceding section in a short time and with a high yield.
  • cysteine hydrochloride and reducing sugars are dissolved in an aqueous solvent, neutralized with sodium hydroxide or the like, and heated to obtain a non-volatile compound.
  • the present inventors have found that a thiazolidine compound can be obtained in a short time and at a high yield of about 80% with respect to cysteine, and based on such findings, the present invention has been completed.
  • the present invention firstly relates to a method for producing a non-volatile thiazolidine compound, which comprises maintaining cysteine or Z and cystinyl glycine and a reducing sugar in an aqueous solvent under heating.
  • the present inventor has further conducted intensive studies to achieve the above object, and found that cystine and reducing sugars were dissolved in an aqueous solvent instead of cysteine and / or cystinylglycine in an aqueous solvent, and the solution was alkalized with sodium hydroxide or the like. It was found that a non-volatile thiazolidine compound can be obtained in a short time and with a high yield of about 80% with respect to cysteine by heating, and the present invention was completed based on such findings.
  • the present invention secondly relates to a method for producing a non-volatile thiazolidine compound, which comprises maintaining cystine and a reducing sugar in an aqueous solvent while heating.
  • the non-volatile thiazolidine compound to be produced by the method of the present invention refers to a non-volatile derivative of thiazolidine having one or more substituents on a thiazolidine skeleton.
  • Oproline and its derivatives and 2- (polyhydroxyalkyl) thiazolidine-4-carboxylic acids specifically, 2- (1,2,3-trihydroxypropyl) thiazolidine-4-carboxylic acid, 2- (1,2 , 3,4-Tetrahydroxybutyl) thiazolidine-4-carboxylic acid, 2- (1,2,3,4,5-pentylhydroxypentyl) thiazolidine-4-carboxylic acid, 2-hydroxymethyl-2- (1 , 2,3,4-Tetrahydroxybutyl) thiazolidine-4-carboxylic acid, 2- (1,2,4,5-tetrahydroxy-3-darcoviranosyloxypentyl) thiazolidine-4-ca Bonic acid, 2- (1,2,3,4-tetrahydroxybutyl) thiazolidine-4-force Luponyl-N-glycine, 2- (1,2,3,4,5-penoxyhydroxypentyl) thiazolidine-4 -Carbonyl-N-glycine and
  • such a non-volatile thiazolidine compound may be a saccharide having a reducing group such as cysteine cis-tinylglycine and a monosaccharide such as xylose or glucose, or a disaccharide such as maltose or lactose.
  • the sugar can be easily obtained by holding the composition in an aqueous solvent under heating, for example, under neutral to neutral conditions.
  • cysteine is preferably an integral L when the target non-volatile thiazolidine compound is used for food.
  • Cysteine is usually used in the form of a hydrochloride salt, because its solubility is better in the form of a salt such as a hydrochloride salt than in the free form.
  • cysteine hydrochloride is usually distributed in the form of monohydrate.
  • cysteine (hydrochloride) must be used as long as the effects of the present invention are achieved. It does not need to be pure, and may be, for example, a yeast extract containing cysteine (hydrochloride).
  • Cystinylglycine has a common chemical structure with cysteine, and exhibits the same chemical behavior as cysteine in the production method of the present invention. For these reasons, cysteine and cystinildaricin can be used alone or as a mixture of both as raw materials for the method for producing a nonvolatile thiazolidine compound of the present invention.
  • cysteine or / and cystinyl glycine and reducing sugars react in equimolar amounts to give the target compound. It is preferable that the content is slightly excessive in view of the yield of cysteine or Z and cysteinylglycine of the objective compound.
  • the temperature to be kept under heating is 40 to 100 ° C, preferably 60 to 80 ° C. At low temperatures, it takes a long time to produce the target substance, while at high temperatures, the target substance can be produced in a short time, but it is not preferable because side reactions such as heating browning reaction easily occur. It is needless to say that cysteine and / or cysteinylglycine and reducing sugar are preferably kept under the above conditions until the production rate of the target compound is maximized. May be around 20 minutes (See Figure 1 below)
  • the target compound thus produced can be separated from the reaction mixture and used for food, but may be used as a reaction mixture (solution) as it is, or may be appropriately dried and powdered for distribution.
  • Sodium chloride produced by the neutralization operation accompanies the reaction mixture and its dry powdered product, but it is clear that it does not particularly hinder its use in foods.
  • the reaction mixture may be added with a solvent such as ethanol, crystallized, filtered and dried, or the reaction solution may be directly subjected to spray drying or freeze drying. It may be dried and powdered.
  • a solvent such as ethanol, crystallized, filtered and dried
  • the reaction solution may be directly subjected to spray drying or freeze drying. It may be dried and powdered.
  • the form of application of the nonvolatile thiazolidine compound thus obtained to foods can be appropriately determined by mixing powders and solutions.
  • the non-volatile thiazolidine compound to be produced by the method of the present invention refers to a non-volatile derivative of thiazolidine having one or more substituents on the thiazolidine skeleton, such as thioproline and its derivatives or 2- ( Polyhydroxyalkyl) thiazolidine-4-carboxylic acids, specifically, 2- (1,2,3-trihydroxypropyl) thiazolidine-4-carboxylic acid, 2- (1,2,3,4-tetrahydroxybutyl) Thiazolidine-4-carboxylic acid, 2- (1,2,3,4,5-pentanohydroxypentyl) thiazolidine-4-carboxylic acid, 2-hydroxymethyl-2- (1,2,3,4-tetra (Hydroxybutyl) thiazolidine-4-carboxylic acid, 2- (1,2,4,5-tetrahydroxy-3-darcopyranosyloxypentyl) thiazolidine-4-carboxylic acid, 2- (1,2,4,5
  • such a non-volatile thiazolidine compound includes cystine and a sugar having a reducing group (reducing sugar) such as monosaccharides such as xylose and glucose, and disaccharides such as maltose and lactose.
  • reducing sugar such as monosaccharides such as xylose and glucose
  • disaccharides such as maltose and lactose.
  • cystine is preferably integrated with L when the non-volatile thiazolidine compound of the target compound is used for food.
  • Cystine may be in the form of free acid or in the form of hydrochloride, and is not necessarily a pure product as long as the effects of the present invention can be obtained.
  • cystine eg, yeast extract containing cystine (hydrochloride)
  • it may be in a form.
  • reducing sugar there is no particular limitation on the reducing sugar, and pentoses such as D-xylose, hexoses such as D-darcose, and disaccharides such as maltose can be used.
  • cystine is cleaved at its SS bond by a reducing sugar, and then the resulting cysteine reacts with the reducing sugar in equimolar amounts to give the target compound. Conceivable. Therefore, the required amount of sugar is considered to be 3 moles per 1 mole of cystine.
  • the reducing sugar is at least 2 moles per mole of cystine, and the use of 2.2 moles can maximize the yield of cystine.
  • the temperature to be kept under heating is 25-100 ° C., preferably 60-90. C. At low temperatures, it takes a long time to produce the target substance, while at high temperatures, the target substance can be produced in a short time, but it is not preferable because side reactions such as heating browning reaction easily occur. Needless to say, it is preferable to maintain cystine and reducing sugar under the above conditions until the production rate of the target compound is maximized, but such a time is, for example, within about 15 minutes from the start of the retention. Sometimes (see Figure 2 below).
  • reducing sugars show reducing properties when they are active, and those which are non-volatile thiazolidine compounds. Because of good stability, pH New However, even if the initial pH starts the reaction from an alkali such as pH 11, the pH rapidly drops at first to about pH 8, for example, and then the non-volatile thiazolidine compound As pH is generated, the pH gradually decreases and changes to a neutral range or a weakly acidic range (eg, pH 6.5).
  • a neutral range or a weakly acidic range eg, pH 6.5.
  • the target compound thus formed can be separated from the reaction mixture and used for food as described above, but it may be used as a reaction mixture (solution) as it is, or may be appropriately dried and powdered. Can be put into circulation.
  • the pulverization method or the drying method There are no particular restrictions on the pulverization method or the drying method. After completion of the reaction, a solvent such as ethanol is added to the reaction mixture, and the crystallized product may be filtered and dried, or the reaction solution may be directly subjected to spray drying or freeze drying. It may be dried and powdered.
  • the form of application of the nonvolatile thiazolidine compound thus obtained to foods can be appropriately determined by mixing powders and solutions. These are the same as described above.
  • FIG. 1 shows the effect of the heating temperature on the production rate of the nonvolatile thiazolidine compound (see Examples 1 and 2).
  • FIG. 2 shows the effect of the amount of added sugar on the production rate of the non-volatile thiazolidine compound (see Example 3).
  • FIG. 3 shows the effect of the type and amount of sugar on the production rate of the nonvolatile thiazolidine compound (see Examples 4, 1 and 3).
  • FIG. 4 shows the effect of the heating temperature on the rate of formation of the nonvolatile thiazolidine compound (see Examples 5 and 6).
  • FIG. 5 shows the effect of the amount of added sugar on the production rate of the non-volatile thiazolidine compound (see Example 7).
  • FIG. 6 shows the effect of the type of sugar on the production rate of the non-volatile thiazolidine compound (see Examples 8 and 6). (Best mode for carrying out the invention)
  • a non-volatile thiazolidine compound was chemically synthesized by the method of Schubert et al. (J. Biol. Chem., 130, 601 (1939)). That is, 17.56 g (10 Ommo 1) of cysteine hydrochloride (monohydrate) and 15.01 (10 Ommo 1) of D-xylose were dissolved in 35 ml of pure water, and 8.36 ml of pyridine (10 Ommo 1) was added. After the addition, the mixture was stirred at room temperature for 72 hours. Then, 300 ml of ethanol was added and the mixture was allowed to stand in a refrigerator, whereupon a paste-like precipitate was formed.
  • Example 1 was repeated in exactly the same manner, except that the temperature was changed to 40 ° C or 80 ° C instead of the temperature of 60 ° C.
  • the results of Examples 1 and 2 are summarized in FIG. From FIG. 1, it can be seen that the retention time under heating at various temperatures and the fate of the formation of the target compound. As can be understood from FIG. 1, the production rate reaches 80% or more at 60 to 80 ° C.
  • the yield refers to the molar yield of the non-volatile thiazolidine compound from cysteine (hydrochloride) or / and cystinyl glycine. In addition, even if the holding time under heating is within 20 minutes, the generation rate is maximized and does not change thereafter.
  • Example 3 Effect of amount of reducing sugar used on formation of target compound
  • Example 1 was repeated exactly the same except that the amount of xylose was changed to 12.5 mmol or 14.0 mmol instead of 10.5 mmol.
  • Figure 2 summarizes the evolution of the production rate of the target compound at the three amounts of xylose used.
  • the xylose gives a production rate of the target compound of 80% or more with respect to cysteine hydrochloride at any of 1.05, 1.2 and 1.4 times the molar amount. In other words, if the amount of xylose is a small excess with respect to cysteine hydrochloride, Is sufficient for the maximum production of Example 4: Effect of sugar type on production of target compound
  • Example 5 In order to examine the effect of the type of sugar on the production of the target compound, relevant data from the above Examples 4, 1, 1 and 3 are collected and summarized in FIG. This indicates that the production rate of the target compound is not significantly affected by the type of sugar. Next, examples of the present invention in which cystine is used as a raw material will be described.
  • Example 5 In order to examine the effect of the type of sugar on the production of the target compound, relevant data from the above Examples 4, 1, 1 and 3 are collected and summarized in FIG. This indicates that the production rate of the target compound is not significantly affected by the type of sugar. Next, examples of the present invention in which cystine is used as a raw material will be described. Example 5
  • Example 5 is replaced with a temperature of 60 ° C. instead of 60 ° C. 98 ° C., 90 ° C., 70 ° C. or 50. The procedure was repeated in exactly the same manner except that C was used.
  • the results of Examples 5 and 6 are summarized in FIG. In FIG. 4, the vertical axis indicates the yield obtained by converting the molar yield for cystine to the molar yield for cysteine (relative to the molar yield of Cys). The horizontal axis indicates the heating and holding time.
  • Figure 4 shows the retention time under heating at various temperatures and the fate of the formation of the target compound. As can be understood from Fig. 4, at 60 to 90 ° C, the production rate reaches 80% or more in the heating and holding time of 30 minutes to 2 hours.
  • Example 7 Effect of amount of reducing sugar used on production of target compound
  • Example 5 was the same as Example 5 except that the temperature was changed to 90 ° C or 50 ° C instead of 60 ° C, and the amount of xylose was changed to 1.1 times or 1.4 times as much as cysteine at each temperature. Exactly the same was repeated.
  • Figure 5 summarizes the evolution of the yield of the target compound for the two amounts of xylose used at each temperature.
  • Figure 5 shows that xylose was 1.1 times higher and 1
  • the production rate of the target compound is about 80% or more with any of the 4-fold molar amount.
  • Example 5 the heating and holding temperature was 60. The procedure was exactly the same except that C was replaced by 70 ° C. and 1.75 g of D-xylose was replaced by 2.10 g (11.7 mmol) of D-glucose.
  • relevant data from the above Examples 8 and 6 are collected and summarized in FIG. This indicates that xylose has a slightly higher production rate of the target compound than glucose.
  • Chicken consommé (Knol) Commercially available chicken consommé soup prepared by adding 600 ml of hot water to two cubes (14 g) The above is described above 3
  • the nonvolatile thiazolidine obtained in Example 1 A reaction mixture of the compound was added so that the concentration at the time of eating was 5 ppm in terms of the non-volatile compound, and the non-added compound was used as a control. An evaluation was performed. As a result, as shown in the table, the preference of the additive was significantly higher than that of the additive-free product.
  • Table 2 Sensory evaluation of chicken consommé soup
  • a non-volatile thiazolidine compound having no problem for food And can be produced in high yield ⁇

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
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Abstract

L'invention concerne un nouveau procédé de production de composé de thiazolidine non volatil, caractérisé en ce qu'il maintient un sucre de réduction avec une cystéine et/ou une cystéinyl-glycine ou une cystine dans un milieu aqueux par chauffage. Grâce à ce procédé, il est possible de produire un composé de thiazolidine non volatil pouvant s'appliquer de manière satisfaisante à des aliments pendant une courte durée à un rendement élevé.
PCT/JP2003/001362 2002-02-28 2003-02-10 Procédé de préparation de composé de thiazolidine non volatil WO2003072587A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU2003207194A AU2003207194A1 (en) 2002-02-28 2003-02-10 Process for producing nonvolatile thiazolidine compound
JP2003571293A JPWO2003072587A1 (ja) 2002-02-28 2003-02-10 不揮発性チアゾリジン化合物の製造方法

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP2002052586 2002-02-28
JP2002-052586 2002-02-28
JP2002-103227 2002-04-05
JP2002103227 2002-04-05

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102132768A (zh) * 2011-03-16 2011-07-27 江南大学 半胱胺盐酸盐缓释放饲料添加剂的制备方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS3716735B1 (fr) * 1959-10-30 1962-10-17
US4430509A (en) * 1982-01-26 1984-02-07 Degussa Aktiengesellschaft Process for the separation of the racemate (R,S)-cysteine

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS3716735B1 (fr) * 1959-10-30 1962-10-17
US4430509A (en) * 1982-01-26 1984-02-07 Degussa Aktiengesellschaft Process for the separation of the racemate (R,S)-cysteine

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
KAZUTOMO IMABORI, TAMIO YAMAKAWA: "Seikagaku Jiten", 1 April 1995, TOKYO KAGAKU DOZIN CO., LTD., pages: 595, XP002967784 *
KIMIKO ANNO, BOBUKO SENO: "Tokagaku no Kiso", 10 August 1995, KODANSHA LTD., pages: 31, XP002967783 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102132768A (zh) * 2011-03-16 2011-07-27 江南大学 半胱胺盐酸盐缓释放饲料添加剂的制备方法

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AU2003207194A1 (en) 2003-09-09
TW200303172A (en) 2003-09-01
JPWO2003072587A1 (ja) 2005-06-16
MY139293A (en) 2009-09-30

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