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    PRODUCTION METHOD FOR OLIGONUCLEOTIDES
    1.
    发明申请
    PRODUCTION METHOD FOR OLIGONUCLEOTIDES 有权

    公开(公告)号：US20210371450A1

    公开(公告)日：2021-12-02

    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
    2.
    发明申请
    OLIGONUCLEOTIDE MANUFACTURING METHOD 有权

    公开(公告)号：US20220235090A1

    公开(公告)日：2022-07-28

    申请号：US17654700

    申请日：2022-03-14

    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.

    METHOD FOR PRODUCING OLIGONUCLEOTIDE HAVING PHOSPHOROTHIOATED SITE
    4.
    发明申请
    METHOD FOR PRODUCING OLIGONUCLEOTIDE HAVING PHOSPHOROTHIOATED SITE 有权

    公开(公告)号：US20220010348A1

    公开(公告)日：2022-01-13

    申请号：US17485785

    申请日：2021-09-27

    Applicant: AJINOMOTO CO., INC.

    Inventor： Taisuke ICHIMARU ,  Daisuke TAKAHASHI ,  Kunihiro HIRAI ,  Ken YAMASHITA

    IPC: C12P19/34 ,  C07H19/10

    Abstract: A method including obtaining a phosphite form or a phosphorous acid diester form by coupling a nucleoside, nucleotide or oligonucleotide wherein a 5′-hydroxy group is not protected, and other group is optionally protected by a protecting group used for nucleic acid synthesis or bonded to a solid phase carrier, and a nucleoside, nucleotide or oligonucleotide wherein a 3′-hydroxy group or a 3′-amino group is modified by a method for forming a phosphite form or a phosphorous acid diester form, and other group is optionally protected by a protecting group used for nucleic acid synthesis in the presence of an antioxidant is useful for producing an oligonucleotide having a phosphorothioated site.

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