• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    A process for deformylation and separation of N-formyl-L- alpha -aspartyl-L-phenylalanine methyl ester from a mixture containing both alpha and beta isomers thereof, which comprises admixing with said isomeric mixture hydrogen peroxide and an organic acid.
    公开号:SU1299515A3
    申请号:SU843783017
    申请日:1984-08-10
    公开日:1987-03-23
    发明作者:Даллатомасина Франко；Ортика Роберто；Джардино Пьетро；Оппичи Эрнесто
    申请人:Фармиталиа Карло Эрба С.П.А. (Фирма)；
    IPC主号:
    专利说明:

    The invention relates to an improved method for the preparation of methyl b-xA-asparagine-b-phenylalanine, which is used in the food industry B as
    sweetening additive.
    The purpose of the invention is to increase the yield and simplify the process.
    The proposed method makes it possible to carry out the separation of isomers at a time when deforming, and to isolate the target product as a sweet dL isomer in high yield (up to 72%)
    Example 1, 40 ml of a 40% aqueous hydrogen peroxide solution, 20 MP of formic acid and 40 ml of a 37% aqueous solution of hydrochloric acid are added at room temperature to a solution of 100 g of methyl ester N-formyl-c - and - L-aspartyl-L-phenylalanine (dL: / 3 isomer in a ratio of 8: 2) in 160 MP of dichloroethane and 40 mp of acetic acid. The mixture is heated at 45 ° C for eight hours and then cooled. The content of the reaction mixture is analyzed by HPLC (high pressure liquid chromatography), which gives methyl-ester-L-acnaptyl-b-phenylalanine (oLAIIM) 231 mg / ml, methyl ester of c-L-acpartil-L-phenylalanine (/ APM) 56.6 mg / ml, K-formyl-o -b-aspartyl-b-feiylalanium methyl ester (FAPM) 18 mg / mp, methyl N-formyl-3H-aspartyl-b-phenyl apanine, ((3 FAPM) 4.6 mg / mp.
    Analytical conditions. Column: Likhrosorb RP 1.8 5 microns (Knauer); length is 250 mm; 4.6 mm inner diameter; eluent: a mixture of phosphate buffer (pH 3, OiO, l) and adetonitrile (87:13 volume / volume); flow rate 1.5 ml / min; column temperature 35 ° C; Buffer composition: 3.4 g, dissolved in 1 l of water and adjusted to pH with H PO. .
    The retention period of the c4-b-asparagine-b-phenylalanine methyl ester was approximately 800 s.
    The yield of ot-L-aspartile-b-phenylalanine methyl ester is 68 g (93%). The reaction mixture is diluted with 500 ml of water, the aqueous layer is separated, the pH is adjusted to 4.5 by the addition of a 20% aqueous solution of sodium hydroxide. the mixture is stirred for one hour at room temperature and oh

    0
    P

    five
    lazy. Free aspartame is precipitated and filtered. 45.3 g of pure compound are obtained in 70% yield, t, III, 233-235 ° C. (decomposed) (ot) -33.2 (acetic acid), HPLC 99%,
    Etc. and meper 2, 80 ml of a 0% aqueous solution. hydrogen peroxide, 60 MP of formic acid and 20 ml of 96% sulfuric acid are added to a solution of 100 g of methyl N-formyl- and f3-L-acnaptil-L-phenylalanine (oL: p isomers ratio of 8: 2) in 300 ml of ethyl acetate and 40 ml of acetic acid. After 24 hours, the analysis of the content of the reaction mixture using HPLC showed: APM 126.9 mg / mp, p APM 31.5 mg / ml, ot FAPM 20.6 mg / mp, EFAMM 5.2 mg / mp.
    The yield of the methyl ester of o - L-acnaptil-b-phenylalanine was 63.5 g (86.9%). After treatment with ka in example 1, pure aspartame is obtained with a yield of 65%,
    Example 3, Acting as in example 1, but using 40 mp of acetic acid instead of formic acid (for 8 hours), pure aspartame is obtained with a yield of 68%,
    Example 4: Operating as in Example I, but using 30 MP of an 85% aqueous solution of phosphoric acid instead of a 37% aqueous solution of hydrochloric acid (45 ° C for 8 hours), pure aspartame is obtained in 72% yield.
    Example 5, Acting as in example 4, but using 60 mp of 40% aqueous hydrogen peroxide solution instead of 40 MP. aqueous hydrogen peroxide solution (for 20 h), pure aspartame is obtained in 70% yield.
    Example 6, 40 MP of a 60% aqueous solution of hydrogen peroxide and 73 g of 3-chloro-benzoic acid are added at 20 ° C to a solution of 100 g of N-formyl-ci methyl ester and / 3-L-α-aspartyl-b-phenylalanine (s: isomer ratio 8: 2) in 1 bO mp dichloroethane and 40 MP acetic acid. The reaction mixture is stirred at 20 ° C. for 24 hours. After the treatment according to Example I, pure aspartame is obtained in 64% yield.
    .3 12995
    权利要求:
    Claims (1)
    [1]
    Formula of gain
    Method of producing methyl ester of L-c (1-asparagine-b of phenylalanine by deforming methyl esters5
    H-formyl-b-asparagine-b-phenylalanine by treating it with a strong acid, characterized in that, in order to increase IVT and simplify the process, a mixture of methyl esters is used as methyl esters of OH-form-3-b-asparagine-b-phenylapanine. L-n / zn-formyl-b-asparagine-b-phenyl-apanine esters, to 1 mole of i. which at 10- is added a mixture containing 1–5 6 moles of hydrogen peroxide, 0.5–10 mol
    Editor And, Shulla
    Compiled by, Volkova
    Tehred M. Morgenthal. Proofreader L. Pilipenko
    Order 906 / 6АТirab 348Subscription
    VNIIPI USSR State Committee
    for inventions and discoveries 113035, Moscow, Zh-35, Raushsk nab., 4/5
    Production and printing company, Uzhgorod, st. Project, 4
    154
    mixtures of organic acids of general formula:
    R - COOH
    where R is hydrogen, 1ml, chlorobenzene, and mineral acid with a dissociation constant at 1.5x10 to 0.1, the latter being taken in a molar ratio of 1-3: I, the process is then carried out at a temperature of from 10 ° C to boiling point the reaction mass, the reaction mass is diluted with water, taken in an amount of 5 May, h. for 1 part of the initial product, the pH is adjusted to 4.5-5.0 by adding alkali, the target product is separated by filtration.
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    同族专利:
    公开号 | 公开日
    GB8420238D0|1984-09-12|
    ZA846148B|1985-03-27|
    CH660013A5|1987-03-13|
    CA1243668A|1988-10-25|
    GB2144748A|1985-03-13|
    US4549987A|1985-10-29|
    DE3428979A1|1985-02-21|
    JPS6067497A|1985-04-17|
    DK163929C|1992-09-14|
    SE8404006D0|1984-08-07|
    FI843112A|1985-02-13|
    AU561635B2|1987-05-14|
    FI81364C|1990-10-10|
    FR2550538B1|1988-03-04|
    NL8402480A|1985-03-01|
    DK381984D0|1984-08-08|
    ATA253784A|1988-04-15|
    GB8321802D0|1983-09-14|
    IL72621D0|1984-11-30|
    IT8422233D0|1984-08-06|
    SE8404006L|1985-02-13|
    DK381984A|1985-02-13|
    FI843112A0|1984-08-08|
    GB2144748B|1987-03-04|
    JPH0676435B2|1994-09-28|
    GR80045B|1984-12-10|
    IT1209577B|1989-08-30|
    BE900317A|1984-12-03|
    FI81364B|1990-06-29|
    FR2550538A1|1985-02-15|
    SE466258B|1992-01-20|
    DE3428979C2|1990-09-06|
    DK163929B|1992-04-21|
    IL72621A|1987-12-20|
    AU3168484A|1985-02-14|
    AT387025B|1988-11-25|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    DE1117134B|1960-06-04|1961-11-16|Berlin Chemie Veb|Process for the preparation of peptides using an oxidatively removable protective group|
    US3492131A|1966-04-18|1970-01-27|Searle & Co|Peptide sweetening agents|
    GB1309605A|1970-01-31|1973-03-14|Ajinomoto Kk|Process for producing alpha-dipeptide esters of l-aspartic acid|
    FR2078640A5|1970-02-21|1971-11-05|Beecham Group Ltd|Alpha-asparaginyl dipeptides prepn|
    BE791544A|1971-11-19|1973-05-17|Stamicarbon|PREPARATION OF ALKYL ESTERS OF DIPEPTIDE|
    US3933781A|1973-11-05|1976-01-20|Monsanto Company|Process for the preparation of α-L-aspartyl-L-phenylalanine alkyl esters|
    JPS5726588B2|1975-08-14|1982-06-05|
    MX4704E|1976-12-27|1982-08-04|Monsanto Co|IMPROVED PROCEDURE FOR THE PREPARATION OF ALPHA-L-ASPARTIL-L-PHENYLALANINE METHYL ESTER|
    JPH0133479B2|1981-02-10|1989-07-13|Ajinomoto Kk|
    JPH0372640B2|1982-04-22|1991-11-19|Ajinomoto Kk|GB8616873D0|1986-07-10|1986-08-20|British Telecomm|Optical telecommunications system|
    DE3635582A1|1986-10-20|1988-04-21|Hoechst Ag|METHOD FOR PURIFYING N-ACYL ASPARTAM|
    US4992272A|1987-03-09|1991-02-12|Diamond Scientific|Canine distemper virus vaccine|
    NL8701035A|1987-05-01|1988-12-01|Stamicarbon|PROCESS FOR THE PREPARATION OF ASPARTYLPHENYLALANINE METHYL ESTER FROM N-FORMYLAS PARTYLPHENYLALANINE METHYL ESTER.|
    JP2662287B2|1988-03-14|1997-10-08|三井東圧化学株式会社|Method for separating α-L-aspartyl-L-phenylalanine methyl ester|
    US5283357A|1988-03-14|1994-02-01|Mitsui Toatsu Chemicals, Incorporated|Separation method of α-l-aspartyl-l-phenylalanine methyl ester|
    JP2979761B2|1991-05-23|1999-11-15|味の素株式会社|Method for producing α-L-aspartyl-L-phenylalanine methyl ester hydrochloride|
    US20080314872A1|2007-06-19|2008-12-25|Ferro Corporation|Chemical-Mechanical Polishing Compositions Containing Aspartame And Methods Of Making And Using The Same|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    GB838321802A|GB8321802D0|1983-08-12|1983-08-12|Aspartame synthesis|
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