公开(公告)号：US10919928B2

公开(公告)日：2021-02-16

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 ,  C07H21/04 ,  C12N15/09 ,  C07H19/167 ,  C07H19/20 ,  C07H1/00 ,  C07H19/10 ,  C07H21/00 ,  C07H19/073 ,  C07H19/173 ,  C07H19/067

Abstract: Oligonucleotides may be produced by a process, including (1) condensing a nucleoside, nucleotide or oligonucleotide (b), and a nucleoside, nucleotide or oligonucleotide (a), or a substituted nucleotide or oligonucleotide (α) 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, wherein said nucleoside, nucleotide or oligonucleotide (a) or said substituted nucleotide or oligonucleotide (α) is a compound represented by formula (a-i): wherein Base, Rp1, R10, m, L, Y, and Z are defined herein.

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.

公开(公告)号：US10464966B2

公开(公告)日：2019-11-05

申请号：US15655280

申请日：2017-07-20

Applicant: AJINOMOTO CO., INC.

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

IPC: C07K1/32 ,  C07H21/02 ,  C07K1/30 ,  C07H21/04 ,  C07H21/00 ,  C07H23/00 ,  C07F7/18 ,  C07C43/10 ,  C07C43/205 ,  C07C49/84 ,  C07C69/157 ,  C07C69/78 ,  C07C233/47 ,  C07D295/108 ,  C07C69/017 ,  C07C69/24 ,  C07C69/757 ,  C07C69/92 ,  C07C69/94 ,  C07C43/23

Abstract: Precipitation promoters, which are an organic compound having one or more linear aliphatic hydrocarbon groups having not less than 10 carbon atoms, wherein the aliphatic hydrocarbon group has not less than 20 carbon atoms in total are useful for precipitating an organic compound protected by an organic group having one or more aliphatic hydrocarbon groups having not less than 10 carbon atoms from a solvent.

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.