Glycoside compound, amidite compound, and production method for polynucleotide using said compounds

Patent metadata

Field	Value
Publication number	US-12509481-B2
Application number	US-202017770520-A
Country	US
Kind code	B2
Filing date	Aug 28, 2020
Priority date	Oct 23, 2019
Publication date	Dec 30, 2025
Grant date	Dec 30, 2025

Abstract

The present invention provides an amidite compound capable of improving a yield and a purity of a polyoligonucleotide, a glycoside compound as an intermediate thereof, and a production method for a polynucleotide using the amidite compound. The present invention also provides an amidite compound of formula (1) capable of improving a yield and a purity of a polyoligonucleotide, a glycoside compound of formula (10) (in formulae (10) and (1), Ba, Ra, Rb, Rc, G1, G2, and G3 are as defined in the description, and R is represented by the following formulae), and a production method for a polynucleotide using the amidite compound.

First claim

The invention claimed is:

1 . An amidite compound represented by formula (1):

wherein R represents a group represented by a formula:

wherein:
R a and R b are identical to or different from each other and each represents a methyl group, an ethyl group, or a hydrogen atom, provided that R a and R b do not represent a hydrogen atom at the same time; and
R c represents a phenyl group which may be substituted with a halogen atom, a methyl group, a nitro group, a methoxy group, or a trifluoromethyl group; a C1 to C10 alkyl group; or a benzyl group,
B a represents a group having an optionally-protected nucleobase structure,
G 1 and G 2 are identical to or different from each other and each represents a protecting group of a hydroxyl group, and
G 3 is identical to or different from each other and each represents an alkyl group.

2 . The amidite compound according to claim 1 , wherein R a represents a methyl group, and R b represents a hydrogen atom.

3 . The amidite compound according to claim 1 , wherein R a and R b both represent a methyl group.

4 . The amidite compound according to claim 1 , wherein G 1 represents the following group:

wherein R 1 , R 2 , and R 3 are identical to or different from each other and each represents hydrogen or an alkoxy group.

5 . The amidite compound according to claim 1 , wherein G 2 represents the following group

6 . The amidite compound according to claim 1 , wherein G 3 represents an isopropyl group.

7 . The amidite compound according to claim 1 , wherein R c represents a phenyl group or a tolyl group.

8 . A production method for a compound containing a polynucleotide structure represented by formula (2), the method comprising a step of using the amidite compound according to claim 1 for a solid-phase synthesis reaction:

wherein B a is identical to or different from each other and each represents a group having an optionally-protected nucleobase structure,
X represents an oxygen atom or a sulfur atom, and
m represents a positive integer.

9 . The production method according to claim 8 , wherein the compound containing a polynucleotide structure of formula (2) is formed by reacting a compound having an oligonucleotide structure represented by formula (3), formed in the solid-phase synthesis reaction using the amidite compound, with a tetraalkylammonium fluoride:

wherein B a , X, and m are as defined in claim 8 ,
and
R is identical to or different from each other and each represents a group represented by a formula:

wherein:
R a and R b are identical to or different from each other and each represents a methyl group, an ethyl group, or a hydrogen atom, provided that R a and R b do not represent a hydrogen atom at the same time; and
R c represents a phenyl group which may be substituted with a halogen atom, a methyl group, a nitro group, a methoxy group, or a trifluoromethyl group; a C1 to C10 alkyl group; or a benzyl group.

10 . The production method according to claim 9 , wherein R a represents a methyl group, and R b represents a hydrogen atom.

11 . An ether compound represented by formula (4):

wherein:
R a and R b are identical to or different from each other and each represents a methyl group, an ethyl group, or a hydrogen atom, provided that R a and R b do not represent a hydrogen atom at the same time;
R c represents a phenyl group which may be substituted with a halogen atom, a methyl group, a nitro group, a methoxy group, or a trifluoromethyl group; a C1 to C10 alkyl group; or a benzyl group; and
R d represents C1 to C10 alkyl or a phenyl group.

12 . The ether compound according to claim 11 , wherein R a represents a methyl group, R b represents a hydrogen atom, and R c represents a phenyl group or a tolyl group.

13 . A production method for an ether compound represented by formula (4), the method comprising step a of reacting a 2-hydroxyalkylsulfone represented by formula (5) with a bisthioether compound represented by formula (12) in a solvent in presence of a halogenating agent and an acid:

wherein:
R a and R b are identical to or different from each other and each represents a methyl group, an ethyl group, or a hydrogen atom, provided that R a and R b do not represent a hydrogen atom at the same time; and
R c represents a phenyl group which may be substituted with a halogen atom, a methyl group, a nitro group, a methoxy group, or a trifluoromethyl group; a C1 to C10 alkyl group; or a benzyl group,

wherein R d represents C1 to C10 alkyl or a phenyl group,

wherein R a , R b , R c , and R d are as defined above.

14 . The production method according to claim 13 , wherein R a represents a methyl group or an ethyl group, R b represents a hydrogen atom, and R c represents a phenyl group or a tolyl group.

15 . The production method according to claim 13 , wherein R a represents a methyl group, R b represents a hydrogen atom, and R c represents a phenyl group or a tolyl group.

16 . A production method for a compound represented by formula (8), the method comprising reacting a compound represented by formula (7) with a compound represented by formula (4) in presence of a halogenating agent:

wherein B a represents a compound having an optionally-protected nucleobase structure, and G 4 represents a protecting group of a hydroxyl group,

wherein R a and R b are identical to or different from each other and each represents a methyl group, an ethyl group, or a hydrogen atom, provided that R a and R b do not represent a hydrogen atom at the same time,
R c represents a phenyl group which may be substituted with a halogen atom, a methyl group, a nitro group, a methoxy group, or a trifluoromethyl group; a C1 to C10 alkyl group; or a benzyl group, and
R d represents C1 to C10 alkyl or a phenyl group,

wherein B a , R a , R b , and R c are as defined above, and G 4 represents a protecting group of a hydrox

Assignees

• Sumitomo Chemical Co

Inventors

• Oshiro Ikuya
• Saito Tatsuya
• Ihara Hideki

Classifications

• C07H21/00

  Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids · CPC title

• C07H19/06

  Pyrimidine radicals · CPC title

• C07C317/18 Primary

  with sulfone or sulfoxide groups bound to acyclic carbon atoms of the carbon skeleton · CPC title

• C07C315/04

  by reactions not involving the formation of sulfone or sulfoxide groups · CPC title

• C07H23/00

  Compounds containing boron, silicon or a metal, e.g. chelates or vitamin B12 (esters with inorganic acids C07H11/00) · CPC title