公开(公告)号：US08304532B2

公开(公告)日：2012-11-06

申请号：US13115845

申请日：2011-05-25

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： C07H21/00

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。

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。

公开(公告)号：US20130303745A1

公开(公告)日：2013-11-14

申请号：US13941272

申请日：2013-07-12

申请人： Meinolf LANGE ,  Andreas HOHLFELD ,  Andreas SCHONBERGER ,  Christina KIRCHHOFF ,  Olaf GROSSEL

发明人： Meinolf LANGE ,  Andreas HOHLFELD ,  Andreas SCHONBERGER ,  Christina KIRCHHOFF ,  Olaf GROSSEL

IPC分类号： C07H21/00

CPC分类号： C07H21/00

摘要： A method for preparing an oligonucleotide comprising the steps of synthesizing a phosphoramidite by reacting a hydroxyl-containing compound of formula (A) with a phosphitylating agent in the presence of an activator compound of formula (I), to prepare a phosphitylated compound, then coupling the 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 selected from the group of imidazole, imidazolium salts, and mixtures thereof, which are improved activators over activators disclosed in related art.

摘要翻译： 一种制备寡核苷酸的方法，其包括通过在式（I）的活化剂化合物存在下使式（A）的含羟基化合物与磷酸化剂反应来合成亚磷酰胺，以制备磷酸化化合物，然后偶联 不分离的具有式（A）的第二化合物的磷酸化化合物，其中R 5，R 3，R 2，B独立地选自但具有与上述相同的定义，在活化剂II存在下，选自咪唑，咪唑鎓 盐及其混合物，它们是相关技术中公开的活化剂的改进的活化剂。