公开(公告)号：WO1996006853A1

公开(公告)日：1996-03-07

申请号：PCT/US1995010609

申请日：1995-08-18

Applicant: BECKMAN INSTRUMENTS, INC.

Inventor： BECKMAN INSTRUMENTS, INC. ,  REDDY, M., Parameswara ,  FAROOQUI, Firdous

IPC: C07H19/10

CPC classification number: C07H19/10 ,  C07H19/20 ,  C07H21/00 ,  Y02P20/55

Abstract: Activated nucleoside derivatives formed in situ of general formula (I) in which one of R and R is R and the other is -P(R2)OR , wherein R is a substituted arylcarbonyl group, R is R O or R , R is a hydroxyl-protecting group and B is a purine or pyrimidine base. Particularly preferred are those compounds wherein R is 2,4-dinitrophenylcarbonyl. The compounds of general formula (I) are prepared using the corresponding carboxylic acids; these acids are generally more soluble in acetonitrile (for example, to the extent of 1.5 M for 2,4-dinitrobenzoic acid) and work as activators at lower concentrations. The compounds of general formula (I) may be employed in conventional coupling reactions (for example, solid phase synthesis) to prepare oligonucleotides which are indistinguishable from those prepared using the heretofore-known tetrazole-activated nucleoside intermediates.

Abstract translation: 活性核苷衍生物原位形成的通式（I）其中R A和R B之一是R 3，另一个是-P（R 2）OR 1，其中R 1是 取代的芳基羰基，R 2是R 4 O或R 5，R 3是羟基保护基，B是嘌呤或嘧啶碱基。 特别优选的是其中R 1是2,4-二硝基苯基羰基的那些化合物。 通式（I）的化合物使用相应的羧酸制备; 这些酸通常在乙腈中更易溶（例如对于2,4-二硝基苯甲酸为1.5M的程度），作为较低浓度的活化剂。 通式（I）的化合物可以用于常规偶合反应（例如固相合成）中，以制备与使用迄今为止已知的四唑活化的核苷中间体制备的寡核苷酸不同的寡核苷酸。

公开(公告)号：WO1995024413A1

公开(公告)日：1995-09-14

申请号：PCT/US1995002831

申请日：1995-03-07

Applicant: BECKMAN INSTRUMENTS, INC.

Inventor： BECKMAN INSTRUMENTS, INC. ,  REDDY, Meda, Parameswara ,  HANNA, Naeem, B. ,  FAROOQUI, Firdous

IPC: C07H19/06

CPC classification number: C07H19/06 ,  C07H19/04 ,  C07H19/16 ,  C07H21/00 ,  Y02P20/55

Abstract: Deoxyribonucleotide and ribonucleotide derivatives of general formula (I), wherein R represents -CR'R"-Ar, in which Ar is selected from the group consisting of unsubstituted or substituted aryl (as hereinafter defined) and R' and R" are independently selected from the group consisting of hydrogen and lower alkyl; one of -R and R is a hydroxyl-protecting group and the other is a group suitable for synthesis of polynucleotides or for attachment of the nucleotide to a solid support; R is selected from the group consisting of hydrogen, -OH and protected hydroxyl; and B represents a divalent radical corresponding to a purine or pyrimidine base. When synthesis is carried out using these derivatives, the deprotection procedure is reduced to an essentially instantaneous process. The derivatives have acceptable shelf life and are very stable to conventional DNA synthesis conditions. Particularly preferred are those compounds wherein Ar is mono- and dihalo-substituted phenyl.

Abstract translation: 通式（I）的脱氧核糖核苷酸和核糖核苷酸衍生物，其中R 1表示-CR'R“-Ar，其中Ar选自未取代或取代的芳基（如下文定义），R'和R” 独立地选自氢和低级烷基; -R 2和R 3之一是羟基保护基，另一个是适于合成多核苷酸或将核苷酸连接到固体支持物上的基团; R 4选自氢，-OH和被保护的羟基; B表示对应于嘌呤或嘧啶碱基的二价基团。 当使用这些衍生物进行合成时，脱保护程序减少到基本上即时的过程。 衍生物具有可接受的保质期，对于常规的DNA合成条件非常稳定。 特别优选的是其中Ar为单取代和二卤代取代的苯基的那些化合物。

公开(公告)号：WO1997040458A2

公开(公告)日：1997-10-30

申请号：PCT/US1997006648

申请日：1997-04-21

Applicant: BECKMAN INSTRUMENTS, INC.

Inventor： BECKMAN INSTRUMENTS, INC. ,  REDDY, M., Parameswara ,  MICHAEL, Maged, A. ,  FAROOQUI, Firdous

IPC: G06F17/30

CPC classification number: C07H21/00 ,  Y02P20/55

Abstract: Universal solid support oligonucleotide synthesis reagents, oligonucleotide synthesis processes, and reagents for cleaving oligonucleotides from solid supports are disclosed. Oligonucleotide synthesis reagents have the following general formula: SS - R - O - R wherein SS is a solid support; R is (a), (b) or (c), where R is hydrogen or alkyl and R is a phosphate protecting group; and R is a ring moiety having vicinal groups -XR and -YR wherein each of X and Y is independently selected from the group consisting of O, S and NH and one of R and R is a blocking moiety and the other is hydrogen or a hydroxy protecting group. Oligonucleotide cleaving reagents include methylamine and/or ammonium hydroxide and trimethylamine.

Abstract translation: 公开了通用固体支持寡核苷酸合成试剂，寡核苷酸合成方法和用于从固体支持物切割寡核苷酸的试剂。 寡核苷酸合成试剂具有以下通式：SS-R 6 -O-R 3其中SS是固体支持物; R 6是（a），（b）或（c），其中R 5是氢或烷基，R 4是磷酸酯保护基; 并且R 3是具有连位-XR 1和-YR 2的环部分，其中X和Y各自独立地选自O，S和NH以及R 1和 R 2是封端部分，另一个是氢或羟基保护基团。 寡核苷酸切割试剂包括甲胺和/或氢氧化铵和三甲胺。

公开(公告)号：WO1995014029A1

公开(公告)日：1995-05-26

申请号：PCT/US1994013331

申请日：1994-11-16

Applicant: BECKMAN INSTRUMENTS, INC.

Inventor： BECKMAN INSTRUMENTS, INC. ,  REDDY, M., P. ,  FAROOQUI, Firdous

IPC: C07H19/06

CPC classification number: C07H19/06 ,  C07H19/10 ,  C07H19/16 ,  C07H19/20 ,  C07H21/00 ,  Y02P20/55

Abstract: Disclosed herein are protecting groups for exocyclic amino groups of the base cytosine for use in the synthesis of oligonucleotides and oligonucleoside phosphorothioates, the protecting groups being represented by the formula: -CO-(CH2)0-9-CH3. In a particularly preferred embodiment, the base cytosine is protected with acetyl (-CO-CH3), and the oligonucleotide or oligonucleoside phosphorothioate incorporating the protected cytosine is subjected to a cleavage/deprotection reagent comprising methylamine and ammonia.

Abstract translation: 本文公开了用于合成寡核苷酸和寡核苷酸硫代磷酸酯的碱基胞嘧啶的环外氨基的保护基团，保护基由式-CO-（CH 2）0-9 -CH 3表示。 在一个特别优选的实施方案中，用乙酰基（-CO-CH 3）保护碱基胞嘧啶，并将含有保护的胞嘧啶的寡核苷酸或寡核苷硫代磷酸酯进行包含甲胺和氨的切割/去保护试剂。

公开(公告)号：EP0725787A1

公开(公告)日：1996-08-14

申请号：EP95930233.0

申请日：1995-08-18

Applicant: BECKMAN INSTRUMENTS, INC.

Inventor： REDDY, M., Parameswara ,  FAROOQUI, Firdous

IPC: C07H19 ,  C07H21

CPC classification number: C07H19/10 ,  C07H19/20 ,  C07H21/00 ,  Y02P20/55

Abstract: Activated nucleoside derivatives formed in situ of general formula (I) in which one of R?A and RB is R3¿ and the other is -P(R¿2)OR?1, wherein R1 is a substituted arylcarbonyl group, R?2 is R4O or R5, R3¿ is a hydroxyl-protecting group and B is a purine or pyrimidine base. Particularly preferred are those compounds wherein R1 is 2,4-dinitrophenylcarbonyl. The compounds of general formula (I) are prepared using the corresponding carboxylic acids; these acids are generally more soluble in acetonitrile (for example, to the extent of 1.5 M for 2,4-dinitrobenzoic acid) and work as activators at lower concentrations. The compounds of general formula (I) may be employed in conventional coupling reactions (for example, solid phase synthesis) to prepare oligonucleotides which are indistinguishable from those prepared using the heretofore-known tetrazole-activated nucleoside intermediates.

公开(公告)号：EP0843684A2

公开(公告)日：1998-05-27

申请号：EP97922372.0

申请日：1997-04-21

Applicant: BECKMAN INSTRUMENTS, INC.

Inventor： REDDY, M., Parameswara ,  MICHAEL, Maged, A. ,  FAROOQUI, Firdous

IPC: C12N15 ,  C07H19 ,  C07H21

CPC classification number: C07H21/00 ,  Y02P20/55

Abstract: Universal solid support oligonucleotide synthesis reagents, oligonucleotide synthesis processes, and reagents for cleaving oligonucleotides from solid supports are disclosed. Oligonucleotide synthesis reagents have the following general formula: SS - R6 - O - R3 wherein SS is a solid support; R6 is (a), (b) or (c), where R5 is hydrogen or alkyl and R4 is a phosphate protecting group; and R3 is a ring moiety having vicinal groups -XR1 and -YR2 wherein each of X and Y is independently selected from the group consisting of O, S and NH and one of R?1 and R2¿ is a blocking moiety and the other is hydrogen or a hydroxy protecting group. Oligonucleotide cleaving reagents include methylamine and/or ammonium hydroxide and trimethylamine.

公开(公告)号：EP0749436A1

公开(公告)日：1996-12-27

申请号：EP95912770.0

申请日：1995-03-07

Applicant: BECKMAN INSTRUMENTS, INC.

Inventor： REDDY, Meda, Parameswara ,  HANNA, Naeem B., Apartment F ,  FAROOQUI, Firdous

IPC: C07H19 ,  C07H21

CPC classification number: C07H19/06 ,  C07H19/04 ,  C07H19/16 ,  C07H21/00 ,  Y02P20/55

Abstract: Deoxyribonucleotide and ribonucleotide derivatives of general formula (I), wherein R1 represents -CR'R'-Ar, in which Ar is selected from the group consisting of unsubstituted or substituted aryl (as hereinafter defined) and R' and R' are independently selected from the group consisting of hydrogen and lower alkyl; one of -R?2 and R3¿ is a hydroxyl-protecting group and the other is a group suitable for synthesis of polynucleotides or for attachment of the nucleotide to a solid support; R4 is selected from the group consisting of hydrogen, -OH and protected hydroxyl; and B represents a divalent radical corresponding to a purine or pyrimidine base. When synthesis is carried out using these derivatives, the deprotection procedure is reduced to an essentially instantaneous process. The derivatives have acceptable shelf life and are very stable to conventional DNA synthesis conditions. Particularly preferred are those compounds wherein Ar is mono- and dihalo-substituted phenyl.