公开(公告)号：US20150112053A1

公开(公告)日：2015-04-23

申请号：US14404562

申请日：2012-05-30

申请人： Shokaku Kim ,  Masanori Matsumoto

发明人： Shokaku Kim ,  Masanori Matsumoto

IPC分类号： C07H21/00 ,  C07H1/00

CPC分类号： C07H21/00 ,  C07H1/00 ,  C07H1/02 ,  C07H1/04 ,  C07H19/073 ,  C07H21/02 ,  C07H21/04 ,  Y02P20/55

摘要： A nucleic acid synthesis method enabling a reaction in a fluid (flow) with a highly dispersible liquid-phase support to improve coupling efficiency is provided.The method for synthesizing an oligonucleotide comprising: sequentially condensing and oxidizing a nucleoside phosphoramidite compound in the presence of an acid/azole complex compound using a starting raw material, i.e., hydrophobic group-bonded nucleoside represented by Formula (1):where R1: an alkylene group having 1 to 12 carbon atoms, R2: an alkylene group having 1 to 22 carbon atoms, R3 and R4 each independently represent an alkyl group having 1 to 22 carbon atoms or the like, R5: a single bond or an alkylene group having 1 to 22 carbon atoms, R6: each independently an alkyl group having 6 to 30 carbon atoms, n represents an integer of 2 to 6, X represents a hydrogen atom, hydroxyl group, or the like, Y: a protecting group deprotectable under an acidic condition, and Z: an adenyl group, a guanyl group, or the like having a polar group optionally protected by a protecting group, wherein a condensation reaction is performed by preliminarily dissolving the hydrophobic group-bonded nucleoside or hydrophobic group-bonded oligonucleotide and the nucleoside phosphoramidite compound in a non-polar solvent, and contacting the resulting solution with the acid/azole complex compound or a solution containing the complex compound.

摘要翻译： 提供了一种使流体（流动）与高度分散的液相载体反应以提高耦合效率的核酸合成方法。 合成寡核苷酸的方法，其包括：使用起始原料，即由式（1）表示的疏水性基团键合的核酸，在酸/唑配合物的存在下，顺序地使核苷亚磷酰胺化合物缩合和氧化：其中R1： 具有1至12个碳原子的亚烷基，R 2：具有1至22个碳原子的亚烷基，R 3和R 4各自独立地表示具有1至22个碳原子的烷基等，R 5：单键或亚烷基，其具有 1〜22个碳原子，R6各自独立地为碳原子数6〜30的烷基，n表示2〜6的整数，X表示氢原子，羟基等，Y表示可以在 酸性条件，Z：具有任选被保护基保护的极性基团的腺苷基，脒基等，其中通过预先将疏水性基团键合的 核苷或疏水基键合的寡核苷酸和核苷亚磷酰胺化合物在非极性溶剂中，并使所得溶液与酸/唑配合物或含有配合物的溶液接触。

公开(公告)号：US09284344B2

公开(公告)日：2016-03-15

申请号：US14404562

申请日：2012-05-30

申请人： Shokaku Kim ,  Masanori Matsumoto

发明人： Shokaku Kim ,  Masanori Matsumoto

IPC分类号： C07H21/00 ,  C07H1/04 ,  C07H1/02 ,  C07H21/04 ,  C07H21/02 ,  C07H1/00 ,  C07H19/073

CPC分类号： C07H21/00 ,  C07H1/00 ,  C07H1/02 ,  C07H1/04 ,  C07H19/073 ,  C07H21/02 ,  C07H21/04 ,  Y02P20/55

摘要： A nucleic acid synthesis method enabling a reaction in a fluid (flow) with a highly dispersible liquid-phase support to improve coupling efficiency is provided.The method for synthesizing an oligonucleotide comprising: sequentially condensing and oxidizing a nucleoside phosphoramidite compound in the presence of an acid/azole complex compound using a starting raw material, i.e., hydrophobic group-bonded nucleoside represented by Formula (1):where R1: an alkylene group having 1 to 12 carbon atoms, R2: an alkylene group having 1 to 22 carbon atoms, R3 and R4 each independently represent an alkyl group having 1 to 22 carbon atoms or the like, R5: a single bond or an alkylene group having 1 to 22 carbon atoms, R6: each independently an alkyl group having 6 to 30 carbon atoms, n represents an integer of 2 to 6, X represents a hydrogen atom, hydroxyl group, or the like, Y: a protecting group deprotectable under an acidic condition, and Z: an adenyl group, a guanyl group, or the like having a polar group optionally protected by a protecting group, wherein a condensation reaction is performed by preliminarily dissolving the hydrophobic group-bonded nucleoside or hydrophobic group-bonded oligonucleotide and the nucleoside phosphoramidite compound in a non-polar solvent, and contacting the resulting solution with the acid/azole complex compound or a solution containing the complex compound.

摘要翻译： 提供了一种使流体（流动）与高度分散的液相载体反应以提高耦合效率的核酸合成方法。 用于合成寡核苷酸的方法，包括：使用起始原料即由式（1）表示的疏水性基团键合的核酸，在酸/唑配合物的存在下，将核苷亚磷酰胺化合物依次缩合和氧化：其中R1： 具有1至12个碳原子的亚烷基，R 2：具有1至22个碳原子的亚烷基，R 3和R 4各自独立地表示具有1至22个碳原子的烷基等，R 5：单键或亚烷基，其具有 1〜22个碳原子，R6各自独立地为碳原子数6〜30的烷基，n表示2〜6的整数，X表示氢原子，羟基等，Y表示可以在 酸性条件，Z：具有任选被保护基保护的极性基团的腺苷基，脒基等，其中通过预先将疏水性基团键合的 核苷或疏水基键合的寡核苷酸和核苷亚磷酰胺化合物在非极性溶剂中，并使所得溶液与酸/唑配合物或含有配合物的溶液接触。

公开(公告)号：US08093435B2

公开(公告)日：2012-01-10

申请号：US12225442

申请日：2007-02-19

申请人： Kazuhiro Chiba ,  Shokaku Kim ,  Yusuke Kono

发明人： Kazuhiro Chiba ,  Shokaku Kim ,  Yusuke Kono

IPC分类号： C07C43/205 ,  C07C321/06 ,  C07C217/58 ,  C07C217/60 ,  C07C217/62

CPC分类号： C07C69/96 ,  C07C67/08 ,  C07C217/58 ,  C07C265/12 ,  C07C275/34 ,  C07C281/20 ,  C07D233/60 ,  C07D487/04 ,  C07F9/5022 ,  C07C69/734

摘要： A reagent for organic synthesis with which a chemical reaction can be conducted in a liquid phase and unnecessary compound(s) can be easily separated at low cost from the liquid phase after completion of the reaction. The reagent for organic synthesis reversibly changes from a liquid-phase state to a solid-phase state with changes in solution composition and/or solution temperature, and is for use in organic synthesis reactions. This reagent for organic syntheses facilitates process development. With the reagent, research on and development of, e.g., medicines through, e.g., compound library synthesis, etc. can be accelerated. It can hence contribute to technical innovations in the biochemical industry and chemical industry.

摘要翻译： 用于在液相中进行化学反应的有机合成试剂和不必要的化合物可以在反应完成后以低成本容易地与液相分离。 有机合成试剂随着溶液组成和/或溶液温度的变化而从液相状态转变为固相状态，并用于有机合成反应。 这种有机合成试剂有利于工艺开发。 通过试剂，可以加速例如通过例如化合物文库合成等的药物的研究和开发。 从而有助于生化工业和化工行业的技术创新。

公开(公告)号：US20100029904A1

公开(公告)日：2010-02-04

申请号：US11992158

申请日：2006-09-20

申请人： Kazuhiro Chiba ,  Shokaku Kim ,  Yusuke Kono

发明人： Kazuhiro Chiba ,  Shokaku Kim ,  Yusuke Kono

IPC分类号： C07C69/76 ,  C07K1/14

CPC分类号： C07K1/306 ,  B01D9/005 ,  C07B63/00 ,  C07B63/02 ,  C07C39/10 ,  C07C41/16 ,  C07C43/23 ,  C07C51/09 ,  C07C51/44 ,  C07C67/60 ,  C07C227/18 ,  C07C227/40 ,  C07C227/42 ,  C07C269/06 ,  C07C269/08 ,  C07K1/042 ,  C07K5/0808 ,  C07C63/331 ,  C07C69/76 ,  C07C229/08 ,  C07C271/22

摘要： A carrier for use for separation purpose and a method for separation of a compound enable a chemical reaction to be performed in a liquid phase, a compound of interest to be separated from the liquid phase after the completion of the reaction readily, the separated compound to be evaluated by structural analysis or the like while the compound is being bound to the carrier, and the compound to be separated from the carrier readily. A carrier for separation is also provided which has a reaction site capable of reacting with other compound(s) on a benzene ring, and a long-chain group having a specified carbon atom(s) at each of the ortho-position and the para-position of the reaction site through an oxygen atom.

摘要翻译： 用于分离目的的载体和化合物的分离方法使得能够在液相中进行化学反应，在反应完成后容易与液相分离的目的化合物，分离的化合物 在化合物与载体结合的同时，通过结构分析等进行评价，容易与载体分离的化合物。 还提供了一种用于分离的载体，其具有能够与苯环上的其它化合物反应的反应位点和在每个邻位和对位具有特定碳原子的长链基团 反应位点通过氧原子。

公开(公告)号：US08633298B2

公开(公告)日：2014-01-21

申请号：US11992158

申请日：2006-09-20

申请人： Kazuhiro Chiba ,  Shokaku Kim ,  Yusuke Kono

发明人： Kazuhiro Chiba ,  Shokaku Kim ,  Yusuke Kono

IPC分类号： C07K1/14 ,  C07K1/04 ,  C07K2/00

CPC分类号： C07K1/306 ,  B01D9/005 ,  C07B63/00 ,  C07B63/02 ,  C07C39/10 ,  C07C41/16 ,  C07C43/23 ,  C07C51/09 ,  C07C51/44 ,  C07C67/60 ,  C07C227/18 ,  C07C227/40 ,  C07C227/42 ,  C07C269/06 ,  C07C269/08 ,  C07K1/042 ,  C07K5/0808 ,  C07C63/331 ,  C07C69/76 ,  C07C229/08 ,  C07C271/22

摘要： A carrier for use for separation purpose and a method for separation of a compound enable a chemical reaction to be performed in a liquid phase, a compound of interest to be separated from the liquid phase after the completion of the reaction readily, the separated compound to be evaluated by structural analysis or the like while the compound is being bound to the carrier, and the compound to be separated from the carrier readily. A carrier for separation is also provided which has a reaction site capable of reacting with other compound(s) on a benzene ring, and a long-chain group having a specified carbon atom(s) at each of the ortho-position and the para-position of the reaction site through an oxygen atom.

摘要翻译： 用于分离目的的载体和化合物的分离方法使得能够在液相中进行化学反应，在反应完成后容易与液相分离的目的化合物，分离的化合物 在化合物与载体结合的同时，通过结构分析等进行评价，容易与载体分离的化合物。 还提供了一种用于分离的载体，其具有能够与苯环上的其它化合物反应的反应位点和在每个邻位和对位具有特定碳原子的长链基团 反应位点通过氧原子。

公开(公告)号：US08293948B2

公开(公告)日：2012-10-23

申请号：US13346175

申请日：2012-01-09

申请人： Kazuhiro Chiba ,  Shokaku Kim ,  Yusuke Kono

发明人： Kazuhiro Chiba ,  Shokaku Kim ,  Yusuke Kono

IPC分类号： C07C43/205 ,  C07C275/30 ,  C07C211/01 ,  C07C69/96 ,  C07C69/76 ,  C07C271/06 ,  C07C229/28 ,  C07C265/12 ,  C07D233/60 ,  C07D487/02

CPC分类号： C07C69/96 ,  C07C67/08 ,  C07C217/58 ,  C07C265/12 ,  C07C275/34 ,  C07C281/20 ,  C07D233/60 ,  C07D487/04 ,  C07F9/5022 ,  C07C69/734

摘要： A reagent for organic synthesis with which a chemical reaction can be conducted in a liquid phase and unnecessary compound(s) can be easily separated at low cost from the liquid phase after completion of the reaction. The reagent for organic synthesis reversibly changes from a liquid-phase state to a solid-phase state with changes in solution composition and/or solution temperature, and is for use in organic synthesis reactions. This reagent for organic syntheses facilitates process development. With the reagent, research on and development of, e.g., medicines through, e.g., compound library synthesis, etc. can be accelerated. It can hence contribute to technical innovations in the biochemical industry and chemical industry.

公开(公告)号：US20120108788A1

公开(公告)日：2012-05-03

申请号：US13346175

申请日：2012-01-09

申请人： Kazuhiro Chiba ,  Shokaku Kim ,  Yusuke Kono

发明人： Kazuhiro Chiba ,  Shokaku Kim ,  Yusuke Kono

IPC分类号： C07K1/02

CPC分类号： C07C69/96 ,  C07C67/08 ,  C07C217/58 ,  C07C265/12 ,  C07C275/34 ,  C07C281/20 ,  C07D233/60 ,  C07D487/04 ,  C07F9/5022 ,  C07C69/734

摘要： A reagent for organic synthesis with which a chemical reaction can be conducted in a liquid phase and unnecessary compound(s) can be easily separated at low cost from the liquid phase after completion of the reaction. The reagent for organic synthesis reversibly changes from a liquid-phase state to a solid-phase state with changes in solution composition and/or solution temperature, and is for use in organic synthesis reactions. This reagent for organic syntheses facilitates process development. With the reagent, research on and development of, e.g., medicines through, e.g., compound library synthesis, etc. can be accelerated. It can hence contribute to technical innovations in the biochemical industry and chemical industry.

摘要翻译： 用于在液相中进行化学反应的有机合成试剂和不必要的化合物可以在反应完成后以低成本容易地与液相分离。 有机合成试剂随着溶液组成和/或溶液温度的变化而从液相状态转变为固相状态，并用于有机合成反应。 这种有机合成试剂有利于工艺开发。 通过试剂，可以加速例如通过例如化合物文库合成等的药物的研究和开发。 从而有助于生化工业和化工行业的技术创新。

公开(公告)号：US20090299103A1

公开(公告)日：2009-12-03

申请号：US12225442

申请日：2007-02-19

申请人： Kazuhiro Chiba ,  Shokaku Kim ,  Yusuke Kono

发明人： Kazuhiro Chiba ,  Shokaku Kim ,  Yusuke Kono

IPC分类号： C07C39/10

CPC分类号： C07C69/96 ,  C07C67/08 ,  C07C217/58 ,  C07C265/12 ,  C07C275/34 ,  C07C281/20 ,  C07D233/60 ,  C07D487/04 ,  C07F9/5022 ,  C07C69/734

摘要： A reagent for organic synthesis with which a chemical reaction can be conducted in a liquid phase and unnecessary compound(s) can be easily separated at low cost from the liquid phase after completion of the reaction. The reagent for organic synthesis reversibly changes from a liquid-phase state to a solid-phase state with changes in solution composition and/or solution temperature, and is for use in organic synthesis reactions. This reagent for organic syntheses facilitates process development. With the reagent, research on and development of, e.g., medicines through, e.g., compound library synthesis, etc. can be accelerated. It can hence contribute to technical innovations in the biochemical industry and chemical industry.

摘要翻译： 用于在液相中进行化学反应的有机合成试剂和不必要的化合物可以在反应完成后以低成本容易地与液相分离。 有机合成试剂随着溶液组成和/或溶液温度的变化而从液相状态转变为固相状态，并用于有机合成反应。 这种有机合成试剂有利于工艺开发。 通过试剂，可以加速例如通过例如化合物文库合成等的药物的研究和开发。 从而有助于生化工业和化工行业的技术创新。