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    Process for the production of optically active compounds having substituents at the 2-position
    4.
    发明申请
    Process for the production of optically active compounds having substituents at the 2-position 审中-公开
    用于制备在2-位具有取代基的光学活性化合物的方法

    公开(公告)号：US20060247458A1

    公开(公告)日：2006-11-02

    申请号：US10546823

    申请日：2004-02-25

    申请人： Shogo Yamamoto ,  Toshihiro Takeda ,  Yoshihide Fuse ,  Yasuyoshi Ueda

    发明人： Shogo Yamamoto ,  Toshihiro Takeda ,  Yoshihide Fuse ,  Yasuyoshi Ueda

    IPC分类号： C07C319/02

    CPC分类号： C07B53/00 ,  C07B2200/07 ,  C07C51/363 ,  C07C319/14 ,  C07C57/58 ,  C07C323/56

    摘要： The present invention provides a process for producing an optically active compound having a thio group at the 2-position important for manufacturing medicines. An optically active compound having a hydroxyl group at the 2-position is chlorinated with inversion of the configuration at the 2-position, and the resultant optically active compound having a chlorine atom at the 2-position is reacted with a metal thiolate to introduce a thio group with inversion of the configuration at the 2-position. This process is capable of minimizing racemization and producing an optically active compound having a thio group at the 2-position at low cost in high yield. When the optically active compound having a chlorine atom at the 2-position is reacted with the metal thiolate in coexistence with water in the reaction system, the optically active compound having a thio group at the 2-position with higher optical purity can be produced in higher yield. An optically active carboxylic acid having a thio group at the 2-position is crystallized in the presence of an aliphatic hydrocarbon solvent and/or a sulfur-containing solvent to effectively remove coexistent impurities such as an optical isomer and the like, thereby producing crystals of an optically active carboxylic acid having a thio group at the 2-position with higher purity.

    摘要翻译： 本发明提供了制造药物重要的2位具有硫基的光学活性化合物的方法。 在2-位上具有羟基的光学活性化合物用2-位反转形式进行氯化，所得2-位上具有氯原子的光学活性化合物与金属硫醇盐反应，引入 硫基与2-位配位反转。 该方法能够使外消旋化最小化，并以高产率以低成本制备在2-位具有硫基的光学活性化合物。 当反应体系中2-位上具有氯原子的光学活性化合物与金属硫醇盐在水中共存时，具有较高光学纯度的2位具有硫基的光学活性化合物可以在 更高的产量。 在脂肪族烃溶剂和/或含硫溶剂的存在下，在2-位具有硫基的光学活性羧酸结晶化，以有效除去共同的杂质如旋光异构体等，从而产生 在2-位具有较高纯度的具有硫基的光学活性羧酸。

    Processes for producing coenzyme Q10
    5.
    发明授权
    Processes for producing coenzyme Q10 有权
    生产辅酶Q10的方法

    公开(公告)号：US09315839B2

    公开(公告)日：2016-04-19

    申请号：US13020500

    申请日：2011-02-03

    申请人： Kazuyoshi Yajima ,  Takahisa Kato ,  Akihisa Kanda ,  Shiro Kitamura ,  Yasuyoshi Ueda

    发明人： Kazuyoshi Yajima ,  Takahisa Kato ,  Akihisa Kanda ,  Shiro Kitamura ,  Yasuyoshi Ueda

    IPC分类号： C12P7/66 ,  C12P7/22

    CPC分类号： C12P7/66 ,  C12P7/22

    摘要： The present invention relates to a process for producing reduced coenzyme Q10 which comprises obtaining microbial cells containing reduced coenzyme Q10 at a ratio of not less than 70 mole % among the entire coenzymes Q10, optionally disrupting the cells and recovering thus produced reduced coenzyme Q10. The present invention also relates to a process for producing oxidized coenzyme Q10 which comprises either recovering oxidized coenzyme Q10 after oxidizing the above-mentioned microbial cells or disrupted product thereof, or recovering reduced coenzyme Q10 from the above-mentioned microbial cells or disrupted product thereof to oxidize thus-obtained reduced coenzyme Q10 thereafter. According to the processes of the present invention, reduced coenzyme Q10 and oxidized coenzyme Q10 can be produced simply on the industrial scale.

    摘要翻译： 本发明涉及一种还原型辅酶Q10的制备方法，其包括在整个辅酶Q10中获得含有还原型辅酶Q10比例不小于70摩尔％的微生物细胞，任选地破坏细胞并回收所生成的还原型辅酶Q10。 本发明还涉及氧化型辅酶Q10的制造方法，该方法包括在氧化上述微生物细胞或其破坏的产物后回收氧化型辅酶Q10，或将还原型辅酶Q10从上述微生物细胞或其破坏性产物回收至 此后氧化由此得到的还原型辅酶Q10。 根据本发明的方法，可以简单地在工业规模上制备还原型辅酶Q10和氧化型辅酶Q10。

    Processes for producing coenzyme Q10
    7.
    发明申请
    Processes for producing coenzyme Q10 有权
    生产辅酶Q10的方法

    公开(公告)号：US20080171373A1

    公开(公告)日：2008-07-17

    申请号：US11981181

    申请日：2007-10-31

    申请人： Kazuyoshi Yajima ,  Takahisa Kato ,  Akihisa Kanda ,  Shiro Kitamura ,  Yasuyoshi Ueda

    发明人： Kazuyoshi Yajima ,  Takahisa Kato ,  Akihisa Kanda ,  Shiro Kitamura ,  Yasuyoshi Ueda

    IPC分类号： C12N9/00

    CPC分类号： C12P7/66 ,  C12P7/22

    摘要： The present invention relates to a process for producing reduced coenzyme Q10 which comprises obtaining microbial cells containing reduced coenzyme Q10 at a ratio of not less than 70 mole % among the entire coenzymes Q10, optionally disrupting the cells and recovering thus-produced reduced coenzyme Q10. The present invention also relates to a process for producing oxidized coenzyme Q10 which comprises either recovering oxidized coenzyme Q10 after oxidizing the above-mentioned microbial cells or disrupted product thereof, or recovering reduced coenzyme Q10 from the above-mentioned microbial cells or disrupted product thereof to oxidize thus-obtained reduced coenzyme Q10 thereafter. According to the processes of the present invention, reduced coenzyme Q10 and oxidized coenzyme Q10 can be produced simply on the industrial scale.

    摘要翻译： 本发明涉及一种还原型辅酶Q 10的制备方法，该方法包括：将全部还原型辅酶Q 10的比例不小于70摩尔％的还原型辅酶Q 10 辅酶Q 10，任选地破坏细胞并回收如此生产的还原型辅酶Q 10。 本发明还涉及一种生产氧化型辅酶Q 10的方法，其包括在氧化上述微生物细胞或其破坏的产物之后回收氧化型辅酶Q 10，或 从上述微生物细胞中回收还原型辅酶Q 10 N或其破坏产物，从而氧化由此得到的还原型辅酶Q 10。 根据本发明的方法，可以简单地在工业规模上制备还原型辅酶Q 10和氧化型辅酶Q 10。

    Process for production of optically active 2-halogeno-carboxylic acids
    8.
    发明申请
    Process for production of optically active 2-halogeno-carboxylic acids 失效
    光学活性2-卤代羧酸的制备方法

    公开(公告)号：US20050176999A1

    公开(公告)日：2005-08-11

    申请号：US10503264

    申请日：2003-02-04

    申请人： Koki Yamashita ,  Toshihiro Takeda ,  Yasuyoshi Ueda

    发明人： Koki Yamashita ,  Toshihiro Takeda ,  Yasuyoshi Ueda

    IPC分类号： C07C51/363 ,  C07C51/41 ,  C07C51/43 ,  C07C53/15 ,  C07C53/16

    CPC分类号： C07C51/412 ,  C07C51/363 ,  C07C51/43 ,  C07C53/19

    摘要： The invention provides processes for producing efficiently optically active 2-halogenocarboxylic acids useful in the preparation of drugs or the like and salts thereof with amines. Specifically an optically active 2-halogenocarboxylic acid is produced by halogenating an optically active amino acid in water in the presence of a hydrophobic organic solvent and nitrous acid with the configuration retained and with the racemization inhibited through the removal of 2-hydroxy-bromocarboxylic acid formed as a by-product; the obtained optically active 2-halogenocarboxylic acid is transferred to an aqueous phase by converting it into a salt thereof with a base, followed by the removal of the organic phase; and the optically active 2-halogenocarboxylic acid is transferred again to an organic solvent phase, followed by the removal of the aqueous phase, whereby an optically active 2-halogenocarboxylic acid is obtained through the removal of a halogen component. Further, a high-quality salt of an optically active 2-halogenocarboxylic acid with an amine can be obtained by a crystallization method wherein the amine is added over the period of ½ hour or longer either continuously or in portions and/or wherein the crystallization solvent consists of a hydrophobic organic solvent and a hydrophilic organic solvent.

    摘要翻译： 本发明提供了可用于制备药物等的有效光学活性2-卤代羧酸的方法及其与胺的盐。 具体地说，光学活性的2-卤代羧酸是通过在疏水性有机溶剂和亚硝酸存在下在水中卤化光学活性氨基酸而形成的，其中保留了结构，并且通过除去形成的2-羟基 - 溴代羧酸来抑制外消旋化 作为副产品; 将得到的光学活性2-卤代羧酸通过将其转化为其盐与碱反应，然后除去有机相，转移到水相中。 并将光学活性2-卤代羧酸再次转移到有机溶剂相中，然后除去水相，由此通过除去卤素组分获得光学活性的2-卤代羧酸。 此外，光学活性2-卤代羧酸与胺的高品质盐可以通过结晶方法获得，其中胺在连续或部分加入0.5小时或更久的时间内和/或其中结晶溶剂 由疏水性有机溶剂和亲水性有机溶剂构成。

    Process for producing 3-amino-2-hydroxypropionic acid derivatives
    9.
    发明授权
    Process for producing 3-amino-2-hydroxypropionic acid derivatives 失效
    3-氨基-2-羟基丙酸衍生物的制备方法

    公开(公告)号：US07057066B2

    公开(公告)日：2006-06-06

    申请号：US10312208

    申请日：2001-06-26

    申请人： Hiroshi Murao ,  Koki Yamashita ,  Toshihiro Takeda ,  Yasuyoshi Ueda

    发明人： Hiroshi Murao ,  Koki Yamashita ,  Toshihiro Takeda ,  Yasuyoshi Ueda

    IPC分类号： C07C229/06 ,  C07C229/34

    CPC分类号： C07D263/20 ,  C07C227/20 ,  C07C227/32 ,  C07C227/42 ,  Y02P20/55 ,  C07C229/22 ,  C07C229/34

    摘要： The present invention provides a process for preparing 3-amino-2-hydroxypropionic acid derivatives (1) which does not use dangerous reagents, is economically advantageous, and is suitable for an industrial production, which process comprises: treating N-protected-3-amino-2-hydroxypropionic acid derivatives (2) having a steric configuration at 2-position carbon reverse to that of derivatives (1) with a leaving group-introducing agent to convert into N-protected-3-aminopropionic acid derivatives (3), then treating the derivatives with a basic substance to convert into substituted-3-amino-2-hydroxypropionic acid derivatives (4) having an inverted steric configuration at 2-position carbon, and then converting the derivatives into 3-amino-2-hydroxypropionic acid derivatives (1).

    摘要翻译： 本发明提供了一种制备不使用危险试剂的3-氨基-2-羟基丙酸衍生物（1）的方法，在经济上是有利的，适用于工业生产，该方法包括：将N-保护的3- 具有与衍生物（1）相反的2-位碳位置的氨基-2-羟基丙酸衍生物（2）与离去基团引入剂转化为N-保护的3-氨基丙酸衍生物（3）， 然后用碱性物质处理衍生物，将其转化成在2-位碳上具有反向立体构型的取代-3-氨基-2-羟基丙酸衍生物（4），然后将其转化为3-氨基-2-羟基丙酸 衍生物（1）。