Granted Patent B2

US 12,509,481 · App. 17/770,520 · Granted Dec 30, 2025

Inventors: Ikuya Oshiro (Osaka, JP); Tatsuya Saito (Osaka, JP); Hideki Ihara (Osaka, JP)

Assignee: SUMITOMO CHEMICAL COMPANY, LIMITED

C07H1/00C07C315/04C07C317/18C07H19/06C07H21/00

Abstract

Claims (76)

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 hydroxyl group.

17 . The production method according to claim 16 , further comprising:

deprotecting the compound of formula (8) to obtain a compound represented by formula (9);

selectively protecting a hydroxyl group at 5′ of the compound of formula (9) to obtain a compound represented by formula (10); and

reacting the compound of formula (10) with a phosphordiamidite represented by formula (11) to obtain an amidite compound represented by formula (1):

wherein B a represents a compound having an optionally-protected nucleobase structure,

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,

wherein B a , R a , R b , and R c are as defined above, and G 1 represents a protecting group of a hydroxyl group,

wherein G 2 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,

wherein B a , G 1 , G 2 , and G 3 are as defined above, and R represents a group represented by a formula:

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

18 . The production method according to claim 16 , wherein G 4 has a G 4 -1 or G 4 -2 structure:

19 . A compound represented by formula (8):

wherein

B a represents a compound having an optionally-protected nucleobase structure,

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

G 4 represents a protecting group of a hydroxyl group.

20 . A compound represented by formula (9):

wherein

B a represents a compound having an optionally-protected nucleobase structure,

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.

21 . A compound represented by formula (10):

wherein

B a represents a compound having an optionally-protected nucleobase structure,

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

G 1 represents a protecting group of a hydroxyl group.

Assignments (1)

Priority Claims (1)

Continuity (1)

References Cited (16)