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    Method for crystallizing .alpha.-L-aspartyl-L-phenylalanine methyl ester
    1.
    发明授权
    Method for crystallizing .alpha.-L-aspartyl-L-phenylalanine methyl ester 失效
    α-L-天冬氨酰-L-苯丙氨酸甲酯的结晶方法

    公开(公告)号：US5347035A

    公开(公告)日：1994-09-13

    申请号：US125193

    申请日：1993-09-23

    申请人： Hidetoshi Wakamatsu ,  Tsuneo Harada ,  Yukio Kunisawa ,  Kiyotaka Oyama

    发明人： Hidetoshi Wakamatsu ,  Tsuneo Harada ,  Yukio Kunisawa ,  Kiyotaka Oyama

    IPC分类号： A23L27/30 ,  C07K1/14 ,  C07K5/06 ,  C07K5/072 ,  C07K5/075 ,  C07C229/00

    CPC分类号： C07K5/0613

    摘要： A method for crystallizing .alpha.-L-aspartyl-L-phenylalanine methyl ester from a hot aqueous solution containing .alpha.-L-aspartyl-L-phenylalanine methyl ester by cooling is disclosed, which comprises (i) continuously supplying a hot aqueous solution of .alpha.-L-aspartyl-L-phenylalanine methyl ester having a concentration such that the content of L-aspartyl-L-aspartyl-L-phenylalanine methyl esters is less than 0.6% by weight based on the weight of .alpha.-L-aspartyl-L-phenylalanine methyl ester in said solution, or if the content of L-aspartyl-L-aspartyl-L-phenylalanine methyl esters is 0.6% by weight or more based on the weight of .alpha.-L-aspartyl-L-phenylalanine methyl ester in said solution, to a crystallization vessel the temperature of which is lowered to that corresponding to the solubility of .alpha.-L-aspartyl-L-phenylalanine methyl ester or less, and (ii) continuously discharging the formed slurry from the crystallization vessel.

    摘要翻译： 公开了一种通过冷却从含有α-L-天冬氨酰-L-苯丙氨酸甲酯的热水溶液中结晶α-L-天冬氨酰基-L-苯丙氨酸甲酯的方法，其包括（i）连续供应热的α水溶液 L-天冬氨酰-L-苯丙氨酸甲酯的浓度使得L-天冬氨酰基-L-天冬氨酰基-L-苯丙氨酸甲酯的含量基于α-L-天冬氨酰-L重量的小于0.6重量％ - 苯丙氨酸甲酯，或者如果L-天冬氨酰基-L-天冬氨酰基-L-苯丙氨酸甲酯的含量基于α-L-天冬氨酰基-L-苯丙氨酸甲酯的重量计为0.6重量％以上 所述溶液加到结晶容器中，该结晶容器的温度降低至与α-L-天冬氨酰基-L-苯丙氨酸甲酯的溶解度或更低的溶解度，和（ii）从结晶容器中连续排出形成的浆料。

    Enzymatic coupling reaction of N-protected-L-aspartic acid and phenylalanine methyl ester
    2.
    发明授权
    Enzymatic coupling reaction of N-protected-L-aspartic acid and phenylalanine methyl ester 失效
    N-保护的L-天冬氨酸和苯丙氨酸甲酯的酶偶联反应

    公开(公告)号：US5693485A

    公开(公告)日：1997-12-02

    申请号：US729507

    申请日：1996-10-11

    申请人： Tsuneo Harada ,  Shigeaki Irino ,  Yukio Kunisawa ,  Kiyotaka Oyama

    发明人： Tsuneo Harada ,  Shigeaki Irino ,  Yukio Kunisawa ,  Kiyotaka Oyama

    IPC分类号： C12P13/04 ,  C07K5/072 ,  C12P21/02 ,  C12P21/00 ,  C07K5/06

    CPC分类号： C07K5/0613 ,  C12P21/02

    摘要： The invention relates to a process for the preparation of N-protected-L-aspartyl-L-phenylalanine methyl ester by enzymatic coupling of an N-protected-L-aspartic acid and L- or DL-phenylalanine methyl ester in an aqueous solution with formation of a precipitate using a thermolysin-like protease enzyme, wherein a water-immiscible organic solvent is added to and blended with the reaction system during the formation of the precipitate in the course of the coupling reaction, which organic solvent has a relatively high affinity for the precipitate. The process is particularly suitable as a continuous process. The method results in lower enzyme deactivation during and after the enzymatic coupling reaction and in larger and thicker precipitated crystals.

    摘要翻译： 本发明涉及通过N-保护的L-天冬氨酸和L-或DL-苯丙氨酸甲酯在水溶液中的酶偶联来制备N-保护的L-天冬氨酰基-L-苯丙氨酸甲酯的方法， 使用嗜热菌蛋白酶蛋白酶形成沉淀物，其中在偶联反应过程中在形成沉淀物期间向反应体系中加入与水不混溶的有机溶剂并与其混合，该有机溶剂具有较高的亲和力 为沉淀。 该方法特别适合作为连续方法。 该方法在酶偶联反应期间和之后以及较大和较厚的沉淀晶体中导致较低的酶失活。