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    • 2. 发明申请
    • Silyl Linker For Solid-Phase Synthesis Of Nucleic Acid
    • 用于固相合成核酸的硅烷基连接剂
    • US20080051571A1
    • 2008-02-28
    • US10590267
    • 2005-02-10
    • Mitsuo SekineKohji SeioAkihiro Ohkubo
    • Mitsuo SekineKohji SeioAkihiro Ohkubo
    • C07H1/00C07F7/02C07H21/00
    • C07H19/173C07F7/0896C07H19/073C07H21/04
    • The purpose of the invention is to develop a silyl linker that can be efficiently introduced on a solid-phase support used for the synthesis of nucleic acid oligomers such as DNA. The present invention relates to a silyl linker for use in the solid-phase synthesis of nucleic acid, comprised of a compound of the general formula or its ester or salt: H—(R1)Si(R2)—(C6H4)—CONH-(A)-COOH   (I) wherein each of R1 and R2 is an alkyl or aryl group, and (A) represents a spacer moiety; a 3′-end nucleoside unit having said compound linked via an oxygen atom to the 3-position of a sugar of the nucleoside or its derivative, a solid-phase support having the 3′-end nucleoside unit, and a method for synthesis of nucleic acid oligomer with the use of said solid-phase support.
    • 本发明的目的是开发可以有效地引入用于合成核酸寡聚物如DNA的固相载体上的甲硅烷基接头。 本发明涉及用于固相合成核酸的甲硅烷基连接体,其由通式或其酯或盐的化合物组成:<?in-line-formula description =“In-line Formulas”end =“铅”→H(R 1)Si(R 2) - (C 6 H 4) - CONH-(A)-COOH(I) -line-formula description =“In-line Formulas”end =“tail”?>其中R1和R2各自为烷基或芳基,(A)表示间隔基; 具有通过氧原子与核苷或其衍生物的糖的3-位连接的所述化合物的3'-末端核苷单元,具有3'-末端核苷单元的固相载体和合成 使用所述固相载体的核酸寡聚物。
    • 3. 发明申请
    • 3'-End Nucleoside Unit Comprising Phosphoramidite
    • 包含亚磷酰胺的3'-末端核苷单位
    • US20080039620A1
    • 2008-02-14
    • US10590268
    • 2005-02-10
    • Mitsuo SekineKohji SeioAkihiro Ohkubo
    • Mitsuo SekineKohji SeioAkihiro Ohkubo
    • C07H21/04C08F8/40
    • C07F9/65616C07F9/65586C07H21/04Y02P20/55
    • The purpose of the present invention is therefore to provide a method for binding a 3′-end nucleoside unit comprising any base to a hydroxyl group on a solid-phase support under completely the same condition as in DNA chain elongation reaction. The present invention relates to a 3′-end nucleoside unit comprising phosphoramidite that is a compound represented by the following formula: (N)—O—(R1)Si(R2)-(C6H4)—(CH2)n-O—P(OR3)N(R4)(R5)  (I) wherein (N) represents any nucleoside or its derivative, each of R1, R2, R4 and R5 is an alkyl or aryl group, R3 is a phosphate-protecting group, and n is an integer of from 1 to 5; a solid-phase support having said 3′-end nucleoside unit; and a method for the synthesis of a nucleic acid oligomer with the use of said solid-phase support.
    • 因此,本发明的目的是提供一种在与DNA链伸长反应完全相同的条件下将包含任何碱基的3'-末端核苷单元与固相载体上的羟基结合的方法。 本发明涉及包含亚磷酰胺的3'-末端核苷单位,该亚磷酰胺是下式表示的化合物:&lt;&lt;线内式记载=“在线式”末端=“铅”→(N) - O-(R 1)Si(R 2) - (C 6 H 4) - (CH 2)nOP(OR 3)N(R 4) 其中(N)表示任何核苷或其衍生物,R 1,R 2,R 4和R 5各自为 烷基或芳基,R3是磷酸酯保护基,n是1至5的整数; 具有所述3'-末端核苷单元的固相载体; 以及使用所述固相载体合成核酸寡聚物的方法。
    • 4. 发明授权
    • 3′-end nucleoside unit comprising phosphoramidite
    • 包含亚磷酰胺的3'-末端核苷单位
    • US07943758B2
    • 2011-05-17
    • US10590268
    • 2005-02-10
    • Mitsuo SekineKohji SeioAkihiro Ohkubo
    • Mitsuo SekineKohji SeioAkihiro Ohkubo
    • C07H19/10C07H19/20
    • C07F9/65616C07F9/65586C07H21/04Y02P20/55
    • Methods of synthesizing nucleic acid oligomers on a solid-phase support having a 3′-end nucleoside unit introduced thereon-as represented by formula II: wherein of formula II represents a 2′-deoxyribonucleoside or its N-protected derivative, the substituent —O—(R1)Si(R2)—(C6H3R6)—(CH2)n—O—P(OR3)XO)—(CH2)n is attached at the 3′ position of the sugar moiety of the nucleoside substituent; each of R1 and R2 is an alkyl or optionally substituted aryl group, wherein the optionally substituted aryl group has a substituent selected from the group consisting of C1-4 alkyl, nitro, cyano, halo and methoxyl; R3 is a protecting group; X is S or O; R7 is H or 4,4′-dimethoxytrityl; each n is an integer of from 1 to 5; and the solid-phase support has hydroxyl groups on its surface.
    • 在其上引入3'-末端核苷单元的固相载体上合成核酸低聚物的方法 - 如式II所示:其中式II表示2'-脱氧核糖核苷或其N-保护的衍生物,取代基-O - (R1)Si(R2) - (C6H3R6) - (CH2)n-O-P(OR3)XO) - (CH2)n连接在核苷取代基的糖部分的3'位置; R 1和R 2各自为烷基或任选取代的芳基,其中任选取代的芳基具有选自C 1-4烷基,硝基,氰基,卤素和甲氧基的取代基。 R3是保护基; X是S或O; R7是H或4,4'-二甲氧基三苯甲基; 每个n是1至5的整数; 并且固相载体在其表面上具有羟基。
    • 5. 发明授权
    • Method for the synthesis of nucleic acid without protecting base moiety
    • 不保护碱基部分合成核酸的方法
    • US07807821B1
    • 2010-10-05
    • US10591172
    • 2005-02-24
    • Mitsuo SekineKohji SeioAkihiro Ohkubo
    • Mitsuo SekineKohji SeioAkihiro Ohkubo
    • C07H21/00
    • C07H21/04
    • A phosphoramidite method for the synthesis of a nucleic acid oligomer without protecting the base moiety characterized in that a 3′ or 5′ hydroxyl group of a nucleotide is reacted with a nucleoside phosphoramidite, a cyclonucleoside phosphoramidite, a 2′-substituted nucleoside phosphoramidite, a 4′-substituted nucleoside phosphoramidite, or a 2′,4′-di-substituted nucleoside phosphoramidite to produce a phosphodiester linkage. The phosphoramidite is contacted with an activator containing both a) hydroxybenzotriazole-1-ol (HOBt), a mono-substituted HOBt, a di-substituted HOBt, or a di-substituted phenol and b) imidazole, tetrazole, benzimidazoletriflate (BIT), 4-ethylthiotetrazole, imidazolium triflate(trifluoromethane sulfonate) or 4,5-dicyanoimidazole.
    • 用于合成核酸寡聚物而不保护碱基部分的亚磷酰胺方法,其特征在于核苷酸的3'或5'羟基与核苷亚磷酰胺,环核苷亚磷酰胺,2'-取代的核苷亚磷酰胺, 4'-取代的核苷亚磷酰胺或2',4'-二取代的核苷亚磷酰胺,以产生磷酸二酯键。 将亚磷酰胺与包含a)羟基苯并三唑-1-醇(HOBt),单取代HOBt,二取代HOBt或二取代苯酚和b)咪唑,四唑,苯并咪唑三氟甲磺酸酯(BIT), 四氟乙磺酸四氢呋喃,三氟甲烷磺酸咪唑鎓或4,5-二氰基咪唑。
    • 6. 发明授权
    • Silyl linker for solid-phase synthesis of nucleic acid
    • 用于固相合成核酸的硅烷基接头
    • US07786296B2
    • 2010-08-31
    • US10590267
    • 2005-02-10
    • Mitsuo SekineKohji SeioAkihiro Ohkubo
    • Mitsuo SekineKohji SeioAkihiro Ohkubo
    • C07H19/00C07H19/048
    • C07H19/173C07F7/0896C07H19/073C07H21/04
    • The purpose of the invention is to develop a silyl linker that can be efficiently introduced on a solid-phase support used for the synthesis of nucleic acid oligomers such as DNA. The present invention relates to a silyl linker for use in the solid-phase synthesis of nucleic acid, comprised of a compound of the general formula or its ester or salt: H—(R1)Si(R2)-(C6H4)—CONH-(A)-COOH  (I) wherein each of R1 and R2 is an alkyl or aryl group, and (A) represents a spacer moiety; a 3′-end nucleoside unit having said compound linked via an oxygen atom to the 3-position of a sugar of the nucleoside or its derivative, a solid-phase support having the 3′-end nucleoside unit, and a method for synthesis of nucleic acid oligomer with the use of said solid-phase support.
    • 本发明的目的是开发可以有效地引入用于合成核酸寡聚物如DNA的固相载体上的甲硅烷基接头。 本发明涉及用于固相合成核酸的甲硅烷基连接体,其由通式或其酯或盐的化合物组成:H-(R1)Si(R2) - (C6H4)-CONH- (A)-COOH(I)其中R1和R2各自为烷基或芳基,(A)表示间隔基; 具有通过氧原子与核苷或其衍生物的糖的3-位连接的所述化合物的3'-末端核苷单元,具有3'-末端核苷单元的固相载体和合成 使用所述固相载体的核酸寡聚物。