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    SYNTHESIS OF OLIGONUCLEOTIDES
    1.
    发明申请
    SYNTHESIS OF OLIGONUCLEOTIDES 审中-公开
    合成寡核苷酸

    公开(公告)号：US20110065909A1

    公开(公告)日：2011-03-17

    申请号：US12836062

    申请日：2010-07-14

    申请人： Meinolf Lange ,  Andreas Schönberger ,  Andreas Hohlfeld ,  Olaf Grössel ,  Christina Kirchhoff ,  Fritz Link

    发明人： Meinolf Lange ,  Andreas Schönberger ,  Andreas Hohlfeld ,  Olaf Grössel ,  Christina Kirchhoff ,  Fritz Link

    IPC分类号： C07H1/00

    CPC分类号： C07H21/00

    摘要： A method for preparing an oligonucleotide comprising the steps ofa) providing a hydroxyl containing compound having the formula (A), b) reacting said compound with a phosphitylating agent in the presence of an activator (activator I) having the formula (I) to prepare a phosphitylated compound; and c) reacting said phosphitylated compound without isolation with a second compound having the formula (A) wherein R5, R3, R2, B are independently selected, but have the same definition as above in the presence of an activator II different from activator I.

    摘要翻译： 一种制备寡核苷酸的方法，包括以下步骤：a）提供具有式（A）的含羟基化合物，b）在具有式（I）的活化剂（活化剂I）存在下使所述化合物与磷酸化剂反应， 制备磷酸化化合物; 和c）不分离的所述磷化物化合物与式（A）的第二种化合物反应，其中R 5，R 3，R 2，B独立选择，但与不同于活化剂I的活化剂II存在下，具有与上述相同的定义。

    PURIFICATION OF OLIGONUCLEOTIDES
    2.
    发明申请
    PURIFICATION OF OLIGONUCLEOTIDES 失效
    纯化寡核苷酸

    公开(公告)号：US20130066061A1

    公开(公告)日：2013-03-14

    申请号：US13421273

    申请日：2012-03-15

    申请人： Olaf Grössel ,  Andreas Hohlfeld ,  Meinolf Lange ,  Fritz Link ,  Andreas Schönberger

    发明人： Olaf Grössel ,  Andreas Hohlfeld ,  Meinolf Lange ,  Fritz Link ,  Andreas Schönberger

    IPC分类号： C07H1/06

    CPC分类号： C07H21/00

    摘要： A method for purifying a protected oligonucleotide comprising the steps of: a) providing a solution of the protected oligonucleotide in at least one solvent A having a boiling point below the boiling point of a solvent B, heating the solution at a temperature of at least 30° C. and below the boiling point of the at least solvent A, adding solvent B until precipitation of a material is visible in the solution, said solvent B being an alcohol having 1 to 6 C-atoms or a diol having 2 to 6 C-atoms, allowing the solution to cool down under stirring until formation of a supernatant and a residue, removing the supernatant or b) providing solvent B, said solvent B being an alcohol having 1 to 6 C-atoms or a diol having 2 to 6 C-atoms, heating solvent B at a temperature above 30° C. and below the boiling point of solvent B, adding a solution of a protected oligonucleotide in at least one solvent A until precipitation of a material is visible in the solution, allowing the solution to cool down under stirring until formation of a supernatant and a residue, removing the supernatant.

    摘要翻译： 一种用于纯化受保护的寡核苷酸的方法，包括以下步骤：a）在至少一种沸点低于溶剂B的沸点的溶剂A中提供被保护的寡核苷酸的溶液，在至少30℃的温度下加热该溶液 ℃，并且低于至少溶剂A的沸点，加入溶剂B直到溶液中可观察到材料沉淀，所述溶剂B是具有1至6个C原子的醇或具有2至6个碳原子的二醇 原子，使溶液在搅拌下冷却直至形成上清液和残余物，除去上清液或b）提供溶剂B，所述溶剂B是具有1至6个碳原子的醇或具有2至6个碳原子的二醇 C原子，加热溶剂B，温度高于30℃，低于溶剂B的沸点，在至少一种溶剂A中加入被保护的寡核苷酸的溶液，直到在溶液中析出材料，使得 解决方案冷却下来 在搅拌下直到形成上清液和残余物，除去上清液。

    SYNTHESIS OF OLIGONUCLEOTIDES
    3.
    发明申请
    SYNTHESIS OF OLIGONUCLEOTIDES 审中-公开
    合成寡核苷酸

    公开(公告)号：US20120322994A1

    公开(公告)日：2012-12-20

    申请号：US13421384

    申请日：2012-03-15

    申请人： Meinolf Lange ,  Andreas Schönberger ,  Andreas Hohlfeld ,  Olaf Grössel ,  Christina Kirchhoff ,  Fritz Link

    发明人： Meinolf Lange ,  Andreas Schönberger ,  Andreas Hohlfeld ,  Olaf Grössel ,  Christina Kirchhoff ,  Fritz Link

    IPC分类号： C07H1/00

    CPC分类号： C07H21/00

    摘要： A method for preparing an oligonucleotide comprising the steps of a) providing a hydroxyl containing compound having the formula (A), b) reacting said compound with a phosphitylating agent in the presence of an activator (activator I) having the formula (I) to prepare a phosphitylated compound; and c) reacting said phosphitylated compound without isolation with a second compound having the formula (A) wherein R5, R3, R2, B are independently selected, but have the same definition as above in the presence of an activator II different from activator I.

    摘要翻译： 一种制备寡核苷酸的方法，包括以下步骤：a）提供具有式（A）的含羟基化合物，b）在具有式（I）的活化剂（活化剂I）存在下使所述化合物与磷酸化剂反应， 制备磷酸化化合物; 和c）不分离的所述磷化物化合物与式（A）的第二种化合物反应，其中R 5，R 3，R 2，B独立选择，但与不同于活化剂I的活化剂II存在下，具有与上述相同的定义。

    PURIFICATION OF OLIGONUCLEOTIDES
    7.
    发明申请
    PURIFICATION OF OLIGONUCLEOTIDES 审中-公开
    纯化寡核苷酸

    公开(公告)号：US20100087635A1

    公开(公告)日：2010-04-08

    申请号：US12568229

    申请日：2009-09-28

    申请人： Olaf Grossel ,  Andreas Hohlfeld ,  Meinolf Lange ,  Fritz Link ,  Andreas Schönberger

    发明人： Olaf Grossel ,  Andreas Hohlfeld ,  Meinolf Lange ,  Fritz Link ,  Andreas Schönberger

    IPC分类号： C07H1/06

    CPC分类号： C07H21/00

    摘要： A method for purifying a protected oligonucleotide comprising the steps of: a) providing a solution of the protected oligonucleotide in at least one solvent A having a boiling point below the boiling point of a solvent B, heating the solution at a temperature of at least 30° C. and below the boiling point of the at least solvent A, adding solvent B until precipitation of a material is visible in the solution, said solvent B being an alcohol having 1 to 6 C-atoms or a diol having 2 to 6 C-atoms, allowing the solution to cool down under stirring until formation of a supernatant and a residue, removing the supernatant or b) providing solvent B, said solvent B being an alcohol having 1 to 6 C-atoms or a diol having 2 to 6 C-atoms, heating solvent B at a temperature above 30° C. and below the boiling point of solvent B, adding a solution of a protected oligonucleotide in at least one solvent A until precipitation of a material is visible in the solution, allowing the solution to cool down under stirring until formation of a supernatant and a residue, removing the supernatant.

    摘要翻译： 一种用于纯化受保护的寡核苷酸的方法，包括以下步骤：a）在至少一种沸点低于溶剂B的沸点的溶剂A中提供受保护的寡核苷酸的溶液，在至少30℃的温度下加热该溶液 ℃，并且低于至少溶剂A的沸点，加入溶剂B直到溶液中可观察到材料沉淀，所述溶剂B是具有1至6个C原子的醇或具有2至6个碳原子的二醇 原子，使溶液在搅拌下冷却直至形成上清液和残余物，除去上清液或b）提供溶剂B，所述溶剂B是具有1至6个碳原子的醇或具有2至6个碳原子的二醇 C原子，加热溶剂B，温度高于30℃，低于溶剂B的沸点，在至少一种溶剂A中加入被保护的寡核苷酸的溶液，直到在溶液中析出材料，使得 解决方案冷却下来 在搅拌下直到形成上清液和残余物，除去上清液。

    Method for preparing oligonucleotides
    8.
    发明申请
    Method for preparing oligonucleotides 审中-公开
    寡核苷酸的制备方法

    公开(公告)号：US20100069623A1

    公开(公告)日：2010-03-18

    申请号：US12417750

    申请日：2009-04-03

    申请人： Ilaria Adamo ,  Cècile Dueymes ,  Andreas Schönberger ,  Jean-Louis Imbach ,  Albert Meyer ,  Francois Morvan ,  Francoise Debart ,  Jean-Jacques Vasseur ,  Meinolf Lange ,  Fritz Link

    发明人： Ilaria Adamo ,  Cècile Dueymes ,  Andreas Schönberger ,  Jean-Louis Imbach ,  Albert Meyer ,  Francois Morvan ,  Francoise Debart ,  Jean-Jacques Vasseur ,  Meinolf Lange ,  Fritz Link

    IPC分类号： C07H21/04

    CPC分类号： C07H21/00 ,  C07H21/02 ,  C07H21/04 ,  Y02P20/55 ,  Y02P20/582

    摘要： A solution phase synthesis method for preparing an oligonucleotide, wherein at least some of the reagents are solid supported. The method suitable for large-scale synthesis comprises coupling a protected compound with a nucleotide derivative having a protection group in the presence of a solid supported activator to give an elongated oligonucleotide with a P(III)-internucleotide bond; optionally processing the elongated oligonucleotide by capping by reaction with a solid supported capping agent and/or by oxidizing or sulfurizing by reaction of the oligonucleotide with a solid supported oxidizing or sulfurization reagent; and removing the protection group. The coupling may include reacting a 3′-protected compound of formula: with a nucleotide derivative having a 5′-protection group, or reacting a 5′-protected compound of formula with a nucleotide derivative having a 3′-protection group.

    摘要翻译： 一种制备寡核苷酸的溶液相合成方法，其中至少一些试剂是固体负载的。 适用于大规模合成的方法包括在保持固体的活化剂存在下将受保护的化合物与具有保护基团的核苷酸衍生物偶联，得到具有P（III） - 核苷酸键的细长寡核苷酸; 任选地通过与固体支持的封端剂反应进行加帽和/或通过寡核苷酸与固体支持的氧化或硫化试剂的反应进行氧化或硫化来加工细长的寡核苷酸; 并移除保护组。 偶联可以包括使下式的3'-保护的化合物与具有5'-保护基团的核苷酸衍生物反应，或使5受保护的式的化合物与具有3'-保护基团的核苷酸衍生物反应。

    Method for preparing oligonucleotides
    9.
    发明申请
    Method for preparing oligonucleotides 审中-公开
    寡核苷酸的制备方法

    公开(公告)号：US20060089494A1

    公开(公告)日：2006-04-27

    申请号：US10522854

    申请日：2003-07-30

    申请人： Ilaria Adamo ,  Cecile Dueymes ,  Andreas Schonberger ,  Jean-Louis Imbach ,  Albert Meyer ,  Francois Morvan ,  Francoise Debart ,  Jean-Jacques Vasseur ,  Meinolf Lange ,  Fritz Link

    发明人： Ilaria Adamo ,  Cecile Dueymes ,  Andreas Schonberger ,  Jean-Louis Imbach ,  Albert Meyer ,  Francois Morvan ,  Francoise Debart ,  Jean-Jacques Vasseur ,  Meinolf Lange ,  Fritz Link

    IPC分类号： C07H21/02 ,  C07H21/04

    CPC分类号： C07H21/00 ,  C07H21/02 ,  C07H21/04 ,  Y02P20/55 ,  Y02P20/582

    摘要： A method for preparing an oligonucleotide comprising the steps of a) providing a 3-protected compound having the formula: wherein B is a heterocyclic base R2 is H, a protected 2-hydroxyl group, F, a protected amino group, an O-alkyl group, an O-substituted alkyl, a substituted alkylamino or a C4′-O2′methylen linkage R3 is OR′3, NHR″3, NR″3R′″3, a 3′-protected nucleotide or a 3′-protected oligonucleotide, R′3 is a hydroxyl protecting group, R″3, R′″3 are independently an amine protecting group, b) reacting said compound with a nucleotide derivative having a 5-proctection group in the presence of a solid supported activator to give an elongated oligonucleotide with a P(III)-internucleotide bond c) optionally processing the elongated oligonucleotide with a P(III)-internucleotide bond by either or both of steps c1) and c2) in any sequence c1) capping preferably by reacting with a solid supported capping agent c2) oxidizing preferably by reacting the oligonucleotide with a solid supported oxidizing reagent d) removing the 5′-protection group.

    摘要翻译： 一种制备寡核苷酸的方法，包括以下步骤：a）提供具有下式的3-保护的化合物：其中B是杂环基R2是H，被保护的2-羟基，F，保护的氨基，O-烷基 基团，O-取代的烷基，取代的烷基氨基或C4'-O2'亚甲基键R3是OR'3，NHR'3，NR'3R“'，3'-保护的核苷酸或3' R'3是羟基保护基，R“3”，“3”独立地是胺保护基，b）使所述化合物与具有5-取代基的核苷酸衍生物在 c）通过任何序列c1）和c2）中任一或两个步骤c1）和c2）任选地用P（III） - 核苷酸键处理细长寡核苷酸 优选通过与固体支持的封端剂c2反应，优选通过使寡核苷酸与固体支持物反应来进行氧化 d）除去5'-保护基。

    Method for the production of a-(alpha-hydroxyalkyl)-1,3 dioxan-5-ones
    10.
    发明授权
    Method for the production of a-(alpha-hydroxyalkyl)-1,3 dioxan-5-ones 有权
    α-（α-羟基烷基）-1,3二恶烷-5-酮的制备方法

    公开(公告)号：US07851639B2

    公开(公告)日：2010-12-14

    申请号：US11629772

    申请日：2005-06-15

    申请人： Nasir Hayat ,  Meinolf Lange ,  Fritz Link ,  Christiane Neuhaus ,  Bernhard Westermann

    发明人： Nasir Hayat ,  Meinolf Lange ,  Fritz Link ,  Christiane Neuhaus ,  Bernhard Westermann

    IPC分类号： C07D319/06

    CPC分类号： C07D319/06

    摘要： A process for the synthesis of compounds of general formulas comprising the step of reacting in the presence of wherein: R=substituted or unsubstituted alkyl, aryl, heterocycles containing one or more O, N, S, P or B; R1 and R2 independently represent H, substituted or unsubstituted alkyl, aryl, heterocycles containing one or more O, N, S, P or B; R′=H, OH, OR or OSiX3, wherein X independently represent alkyl or aryl.

    摘要翻译： 一种用于合成通式化合物的方法，包括在其中：R =取代或未取代的烷基，芳基，含有一个或多个O，N，S，P或B的杂环的反应的步骤; R 1和R 2独立地表示H，取代或未取代的烷基，芳基，含有一个或多个O，N，S，P或B的杂环; R'= H，OH，OR或OSiX 3，其中X独立地表示烷基或芳基。