OLIGONUCLEOTIDE PRODUCTION METHOD, AND NUCLEOSIDE, NUCLEOTIDE, OR OLIGONUCLEOTIDE

    公开(公告)号:US20180282365A1

    公开(公告)日:2018-10-04

    申请号:US16009533

    申请日:2018-06-15

    IPC分类号: C07H21/02

    摘要: 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.

    OLIGONUCLEOTIDE MANUFACTURING METHOD
    6.
    发明申请

    公开(公告)号:US20180291056A1

    公开(公告)日:2018-10-11

    申请号:US16014536

    申请日:2018-06-21

    IPC分类号: C07H21/04

    摘要: 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.