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    OLIGONUCLEOTIDE PRODUCTION METHOD, AND NUCLEOSIDE, NUCLEOTIDE, OR OLIGONUCLEOTIDE
    3.
    发明申请
    OLIGONUCLEOTIDE PRODUCTION METHOD, AND NUCLEOSIDE, NUCLEOTIDE, OR OLIGONUCLEOTIDE 审中-公开

    公开(公告)号：US20180282365A1

    公开(公告)日：2018-10-04

    申请号：US16009533

    申请日：2018-06-15

    Applicant: AJINOMOTO CO., INC.

    Inventor： Kunihiro HIRAI ,  Satoshi Katayama ,  Naoko Hirose ,  Taisuke Ichimaru ,  Ken Yamashita ,  Daisuke Takahashi

    IPC: C07H21/02

    Abstract: Oligonucleotides may be produced by a process, including (1) condensing a nucleoside, nucleotide or oligonucleotide (a) or the like wherein a 5′-hydroxy group is not protected and a nucleoside, nucleotide or oligonucleotide (b) wherein a 5′-hydroxy group is protected in a non-polar solvent to give a reaction solution containing a phosphite triester product (c); (3) oxidizing or sulfurizing the phosphite triester product (c) to give a reaction solution containing an oligonucleotide (d) wherein the 5′-hydroxy group is protected; (4) deprotecting the oligonucleotide (d) to give a reaction solution containing an oligonucleotide (e) wherein the 5′-hydroxy group is not protected; and (6) adding a polar solvent to the reaction solution containing the oligonucleotide (e) and purifying the oligonucleotide (e) by solid-liquid separation or extraction.

    Production method for oligonucleotides
    4.
    发明授权
    Production method for oligonucleotides 有权

    公开(公告)号：US12269841B2

    公开(公告)日：2025-04-08

    申请号：US17400488

    申请日：2021-08-12

    Applicant: AJINOMOTO CO., INC.

    Inventor： Daisuke Takahashi ,  Taisuke Ichimaru ,  Kunihiro Hirai

    IPC: C07H21/00 ,  C07H1/00

    Abstract: A method for producing an oligonucleotide, including a step of removing a temporary protecting group of a 5′-hydroxyl group by adding an acid to a protected oligonucleotide having a phosphorothioate (PS), phosphate (PO) or H-phosphonate moiety, and deacylating a by-product having an acylated 5′-hydroxyl group by solvolysis can complete a condensation reaction to improve a condensation yield, and can markedly reduce impurities such as single base deletion form (N-1mer) and the like.

    OLIGONUCLEOTIDE MANUFACTURING METHOD
    7.
    发明申请
    OLIGONUCLEOTIDE MANUFACTURING METHOD 审中-公开

    公开(公告)号：US20180291056A1

    公开(公告)日：2018-10-11

    申请号：US16014536

    申请日：2018-06-21

    Applicant: AJINOMOTO CO., INC.

    Inventor： Ken YAMASHITA ,  Kunihiro Hirai ,  Satoshi Katayama ,  Taisuke Ichimaru ,  Daisuke Takahashi ,  Naoko Hirose

    IPC: C07H21/04

    Abstract: The present invention aims to provide a more stable and efficient method for producing oligonucleotide, particularly, oligonucleotide having various functional groups linked to the 3′-terminal and the like. Efficient production of oligonucleotide becomes possible by a production method of an oligonucleotide represented by the formula (Ia-2) (each symbol is as defined in the DESCRIPTION) and having a functional group at the 3′-terminal, the method including a step of subjecting an oligonucleic acid with 3′-terminal protected by a silyl-protecting group to 3′-terminal-selective deprotection under desilylation conditions that do not affect protecting groups other than the silyl group, subjecting same to phosphitylation conditions with a phosphoramidite reagent that do not affect protecting groups on the oligonucleic acid to give a 3′-terminal-phosphoramidited oligonucleotide represented by the formula (Ia-1) (each symbol is as defined in the DESCRIPTION), and linking a functional group to the 3′-terminal of the 3′-terminal phosphoramidited oligonucleotide directly or via a linker, and the like.

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