• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
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    • 专利摘要:
    1506067 Preparation of D-carbamoylamino acids; the corresponding D-amino acids SNAMPROGETTI SpA 11 May 1976 [12 May 1975] 19444/76 Addition to 1452591 Heading C2C The invention comprises a process for producing a D-carbamoyl amino acid of Formula I wherein X is H, halogen, OH, NO 2 , alkoxy, carboxy or a hydrocarbon radical by enzymatic hydrolysis of a racemic hydantoin of Formula II in the presence of, as enzyme, hydropyrimidine hydrolase obtained from calf liver at a pH in the range 8 to 9, and optionally hydrolysing the product by boiling in water to obtain the free amino acid of Formula III
    公开号:SU784761A3
    申请号:SU762356810
    申请日:1976-05-12
    公开日:1980-11-30
    发明作者:Чечере Франческо；Гилли Джулиано；Делла Пенна Джино；Раппуоли Бруно
    申请人:Снампрогетти С.П.А. (Фирма)；
    IPC主号:
    专利说明:

    54) METHOD OF OBTAINING D-AMINO ACIDS
    This invention relates to a novel process for the preparation of D-amino acids used as intermediates in the synthesis of biochemical preparations. Chemical methods known hitherto for separating optical antipodes or enantiomers are based on the use of camphosulfonic acid. . A known method for producing R-amino acids concludes with hydrolysis of the substituted hydantoin in the presence of dihydropyrimidinase at pH 6-11 to R-carbamyl amino acids and then hydrolyzing it in an aqueous medium at boiling to the corresponding R-amino acid l. Also known is the closest to the technical essence of the proposed method of obtaining 0-1 -MINO ACID by enzymatic splitting of racemates into optical antipsad in a buffer solution at .2. The disadvantage of this method is its multistage, which implies the need to preliminarily obtain racemates of amino acids and their subsequent cleavage. The purpose of the invention is to simplify the process. The goal is achieved by the fact that hydantoins of the formula / co-in CH (1 Wl-CO where X is OH and SIS undergo enzymatic hydrolysis by hydropyrimidine hydrolase from bovine liver at pH 8-9 and the resulting carbamylamino acid is hydrolyzed at boiling, preferably the process is wire t at 10-70 ° C. The required pH is maintained by adding alkali as the reaction proceeds. Example 1. 176 g (1 mol) of DL-5-phenylhydantoin are stirred in 7.5 l of a 0.1 M solution (potassium phosphate buffer at pH 8.5 and. 125 ml of a solution of hydropyrimidine hydrolase are added to the suspension and from the liver (total activity 1875 µmol / min at pH 8.5, proteins - 2.75 g). After 6 hours, 250 ml of 4 M are added to maintain a constant pH, the NaOH is stopped and the mixture is then cooled to 37 4C and the pH is adjusted to 5.5 by adding 6N HC | "During the operation, a lumpy precipitate of denatured proteins is formed, which is separated by centrifugation. The floating layer is again cooled down to 4C and the RP is adjusted to 2.5 by adding bn HC2. During the operation, crystals are precipitated, which are washed with approximately 1 liter of underwater (underground water and dried to constant weight). The product is recrystallized from ethanol – water mixture 70:30 (by volume) with heating. The product (189 g, yield 97 %) chromathographically homogeneous, and based on the analysis of the IR, NMR mass spectrum, as well as elementary analysis, it was found that it represents DN-carbamy-Lphenylglycine (18E g, 97% yield), chromatographic homogeneous. the ability of rotation Cdl. 137 (with 1% v, 1n).: Example 2. in the reactor, supplying a thermostatic jacket with an inlet for nitrogen, a pH meter electrode and an inlet for adding soda, added 10 liters of a 0.1 M phosphate buffer solution, which contains hydropyramidehydrolase from the liver (total activity 7500 µmol / min, proteins 11 g). After sparging nitrogen for 30 minutes, 192 g (1 mol) of DL-5-n hydroxyphenylhydantoin is added to the solution at 30 ° C while maintaining a constant pH by adding 4 M NaOH. Twenty hours after the consumption of soda in an amount of 250 ml, D (-) - N-carbamyl-p-hydroxyphenylglydine was separated according to the procedure of Example 1. The resulting product was recrystallized from ethanol (n-hexane). 152 g were obtained (yield 72%) product with the following properties: so pl. -170 ° (with 0.5% in water). Example 3. 206 g (1 mol) of DL-5-p-methoxyphenylhydrantoin is mixed in 10 liters of 0.1 M potassium phosphate buffer at pH 8.5 and 30 ° C, containing hydropyrimidine hydrolase from the liver (activity 7500 μmol / min, proteins - 11 g). Constant pH is maintained by the addition of 4 M NaOH. After 20 h after consumption of 250 ml of soda, the reaction is stopped and the D (-) - N-carbamyl pm oxyphenylglycine is reduced by the procedure of Example 1 in a 90% yield. Example 4. A 230 ml solution of hydropyrimidine hydrolase from the liver with an activity of 10,800 mol / min and 3.45 g of proteins is added to a 2.1 kg solution of 150 g of cellulose triacetate in methyl: 1: loride and thoroughly mixed. An emulsion is obtained which is centrifuged. The obtained fiber (300 g) was introduced in the form of a skein into a glass column with a case (diameter 8 cm, height 60 cm) and fixed both ends with two stainless steel brackets. The fiber is washed by recycling 4 L of 0, .1 M potassium phosphate buffer (pH 8.5) until the enzymatic activity disappears in solution (4 washes, in total, for 6 hours). The fiber column is then placed in a circuit containing a peristaltic pump to recirculate the reaction mixture, the double-walled vessel must have an electrode to constantly check the pH and enter to add 4 M NaOH, operating at a constant pH. 5 liters of 0.02 M phosphate buffer at a pH of 8.5 and 176 g (1 mol) of DL-5-phenylhydantoin are introduced into the system and the pump is turned on to recycle the reaction mixture. After bh after the addition of 4 M NaOH in an amount of 250 ml, the reaction is stopped. The reaction mixture is discharged. The fiber is washed with 4 liters of water. A mixture of water and fiber is concentrated in vacuo to 3 l, cooled to 2c and treated with bn. HCE to pH 2.5. After 30 minutes digestion, the precipitate is collected on a filter and dried to constant weight. The resulting product, 180 g (93% yield) is D - () - M-carbamylphenylglycene (m.p. 2QO C; lcL -135 ° (from 1% in 1N NH40H). Frozen. Proceed as in Example 4 to obtain D - (-) - N-carbamyl-p-hydroxyphenylglycine from DL-5-p-hydroxyphenylhydantoin, but the double vessel is closed and the feed is added for nitrogen. Of the 192 g (1 mol), one oxy-phenylhydantoin is obtained described above 160 g (76% yield) D - (-) - N-carbamyl-p-hydroxyphenylglycine (mp. 200 ° C, -175 ° (from 0.6% in alcohol - 50:50 vol / vol). Example 6. Proceed as in Example 4. From 206 g (1 mol) of DL-5-p-methoxyphenylhydantoin, 200 g are obtained (yield 89%) O (- A) -N-carbamyl-p-methoxyphenylglycine. Example 7. 194 g (1 mol) of D (-) - N-carbamylphenylglycine prepared in Example 4 is mixed with 5 liters of water. The suspension is adjusted to pH 4 with a saturated NagCO solution The suspension is boiled for 8 hours. Then the hot solution is separated from the resin, concentrated in vacuo to 1 l, cooled and treated with 6N HC to pH 2. The resulting product is collected on a filter, washed with water and dried in vacuum to constant weight.
    权利要求:
    Claims (2)
    [1]
    Claim
    1. A method for producing D-amino acids, characterized in 15 that, in order to simplify the process, a compound of formula wherein X - OH, H or CH E is subjected to enzymatic hydrolysis gidropirimidingidrolazoy from calf liver at pH 8-9 and the resulting karbamilaminokislotu hydrolyzed by boiling.
    [2]
    2. The method of pop. 1, characterized in that the process is carried out at 10-70 * C.
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    同族专利:
    公开号 | 公开日
    AU502568B2|1979-08-02|
    NO149779C|1984-06-20|
    YU118276A|1982-02-28|
    DE2621076A1|1976-11-25|
    IT1046399B|1980-06-30|
    AU1371376A|1977-11-10|
    DE2621076B2|1980-04-17|
    NO149779B|1984-03-12|
    SE7605429L|1976-11-13|
    JPS51139687A|1976-12-02|
    FR2310986B2|1978-09-01|
    DK208776A|1976-11-13|
    NO761621L|1976-11-15|
    JPS576912B2|1982-02-08|
    NL7605081A|1976-11-16|
    LU74912A1|1977-07-11|
    ZA762783B|1977-04-27|
    CS209871B2|1981-12-31|
    CA1069844A|1980-01-15|
    HU178336B|1982-04-28|
    YU39038B|1984-02-29|
    GB1506067A|1978-04-05|
    DD125069A6|1977-03-30|
    FR2310986A2|1976-12-10|
    BE841750A|1976-11-12|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    IT987278B|1973-05-11|1975-02-20|Snam Progetti|PROCEDURE FOR THE PREPARATION OF L CARBAMIL AMINO ACIDS AND THE CORRESPONDING L AMINO ACIDS|JPS5545195B2|1976-02-04|1980-11-17|
    EP0001319A1|1977-08-18|1979-04-04|Beecham Group Plc|Process for the preparation of hydroxyphenyl hydantoin and of hydroxyphenyl glycine, and compounds thus obtained|
    JPH0239B2|1984-09-17|1990-01-05|Kanegafuchi Chemical Ind|
    IT1276163B1|1995-11-23|1997-10-27|Eniricerche Spa|IMPROVED PROCEDURE FOR THE PREPARATION OF D-ALPHA-AMINO ACIDS|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    IT23202/75A|IT1046399B|1975-05-12|1975-05-12|PROCEDURE FOR THE PREPARATION OF D CARBAMY AMINO ACIDS AND THE CORRESPONDING D AMINO ACIDS|
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